Publications by authors named "Enrico Bollito"

68 Publications

Are tyrosine kinase inhibitors an effective treatment in testicular metastases from kidney cancer? Case report.

Tumori 2021 Dec 11;107(6):NP149-NP154. Epub 2021 Nov 11.

Department of Oncology, University of Turin, at Division of Medical Oncology, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

Testicular metastases from renal cell carcinoma (RCC) are extremely rare. Tyrosine kinase inhibitors (TKI) are the cornerstone of systemic therapy for metastatic RCC. We report a case of testicular metastasis in a 72-year-old patient with RCC that developed 17 years after nephrectomy and response to TKI treatment, a retrospective literature search on testicular metastases from RCC, and the indirect evidence described in the literature on the efficacy of chemotherapy and target therapy on testicular lesions.
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http://dx.doi.org/10.1177/03008916211059230DOI Listing
December 2021

A Fully Automatic Artificial Intelligence System Able to Detect and Characterize Prostate Cancer Using Multiparametric MRI: Multicenter and Multi-Scanner Validation.

Front Oncol 2021 1;11:718155. Epub 2021 Oct 1.

Department of Radiology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.

In the last years, the widespread use of the prostate-specific antigen (PSA) blood examination to triage patients who will enter the diagnostic/therapeutic path for prostate cancer (PCa) has almost halved PCa-specific mortality. As a counterpart, millions of men with clinically insignificant cancer not destined to cause death are treated, with no beneficial impact on overall survival. Therefore, there is a compelling need to develop tools that can help in stratifying patients according to their risk, to support physicians in the selection of the most appropriate treatment option for each individual patient. The aim of this study was to develop and validate on multivendor data a fully automated computer-aided diagnosis (CAD) system to detect and characterize PCas according to their aggressiveness. We propose a CAD system based on artificial intelligence algorithms that a) registers all images coming from different MRI sequences, b) provides candidates suspicious to be tumor, and c) provides an aggressiveness score of each candidate based on the results of a support vector machine classifier fed with radiomics features. The dataset was composed of 131 patients (149 tumors) from two different institutions that were divided in a training set, a narrow validation set, and an external validation set. The algorithm reached an area under the receiver operating characteristic (ROC) curve in distinguishing between low and high aggressive tumors of 0.96 and 0.81 on the training and validation sets, respectively. Moreover, when the output of the classifier was divided into three classes of risk, i.e., indolent, indeterminate, and aggressive, our method did not classify any aggressive tumor as indolent, meaning that, according to our score, all aggressive tumors would undergo treatment or further investigations. Our CAD performance is superior to that of previous studies and overcomes some of their limitations, such as the need to perform manual segmentation of the tumor or the fact that analysis is limited to single-center datasets. The results of this study are promising and could pave the way to a prediction tool for personalized decision making in patients harboring PCa.
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http://dx.doi.org/10.3389/fonc.2021.718155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517452PMC
October 2021

Molecular Characterization of Prostate Cancers in the Precision Medicine Era.

Cancers (Basel) 2021 Sep 24;13(19). Epub 2021 Sep 24.

Interdisciplinary Group for Translational Research and Clinical Trials, Urological Cancers (GIRT-Uro), Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060 Turin, Italy.

Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients' outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era.
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http://dx.doi.org/10.3390/cancers13194771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507555PMC
September 2021

Adrenal Rests in the Uro-genital Tract of an Adult Population.

Endocr Pathol 2021 Sep 7;32(3):375-384. Epub 2021 Jun 7.

Pathology Unit, Department of Oncology, Città Della Salute E Della Scienza Hospital, University of Turin, Turin, Italy.

Ectopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approximately 0.07% of the total number of urogenital and gynecological surgeries performed in the 22 considered years. Adrenal rests were identified in the spermatic cord (10 males) and in paraovarian, parasalpingeal, or infundibulopelvic ligament locations (30 females). All but one was incidental findings. One case regarded an adrenocortical carcinoma arisen in adrenal rests. A literature review of adrenal ectopia in the urogenital tract of adults identified 57 reported cases from 53 patients, with similar clinicopathological features as those of our series, with the exception of a lower incidence of parasalpingeal locations. Despite their limited clinical implications, awareness of ectopic adrenal rests is essential also in adults for at least two reasons: (a) to correctly identify sources of adrenocortical hormone production in case of adrenal insufficiency or hormonal imbalance and (b) to avoid misinterpretations in the diagnostic workup of renal cell carcinoma, adrenocortical tumors, and rare gonadal neoplasms, including Sertoli/Leydig cell tumors.
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http://dx.doi.org/10.1007/s12022-021-09685-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370964PMC
September 2021

Diagnostic Accuracy of Single-plane Biparametric and Multiparametric Magnetic Resonance Imaging in Prostate Cancer: A Randomized Noninferiority Trial in Biopsy-naïve Men.

Eur Urol Oncol 2021 12 21;4(6):855-862. Epub 2021 Apr 21.

Department of Urology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

Background: Urological guidelines recommend multiparametric magnetic resonance imaging (mpMRI) in men with a suspicion of prostate cancer (PCa). The resulting increase in MRI demand might place health care systems under substantial stress.

Objective: To determine whether single-plane biparametric MRI (fast MRI) workup could represent an alternative to mpMRI in the detection of clinically significant (cs) PCa.

Design, Setting, And Participants: Between April 2018 and February 2020, 311 biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination were randomly assigned to 1.5-T fast MRI (n = 213) or mpMRI (n = 98).

Intervention: All MRI examinations were classified according to Prostate Imaging-Reporting and Data System (PI-RADS) version 2. Men scored PI-RADS 1-2 underwent 12-core standard biopsy (SBx) and those with PI-RADS 4-5 on fast MRI or PI-RADS 3-5 on mpMRI underwent targeted biopsy in combination with SBx. Equivocal cases on fast MRI (PI-RADS 3) underwent mpMRI and then biopsy according to the findings.

Outcome Measurements And Statistical Analysis: The primary outcome was to compare the detection rate of csPCa in both study arms, setting a 10% difference for noninferiority. The secondary outcome was to assess the role of prostate-specific antigen density (PSAD) in ruling out men who could avoid biopsy among those with equivocal findings on fast MRI.

Results And Limitations: The overall MRI detection rate for csPCa was 23.5% (50/213; 95% confidence interval [CI] 18.0-29.8%) with fast MRI and 32.7% (32/98; 95% CI 23.6-42.9%) with mpMRI (difference 9.2%; p = 0.09). The reproducibility of the study could have been affected by its single-center nature.

Conclusions: Fast MRI followed by mpMRI in equivocal cases is not inferior to mpMRI in the detection of csPCa among biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination. These findings could pave the way to broader use of MRI for PCa diagnosis.

Patient Summary: A faster MRI (magnetic resonance imaging) protocol with no contrast agent and fewer scan sequences for examination of the prostate is not inferior to the typical MRI approach in the detection of clinically significant prostate cancer. If our findings are confirmed in other studies, fast MRI could represent a time-saving and less invasive examination for men with suspicion of prostate cancer. This trial is registered at ClinicalTrials.gov as NCT03693703.
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http://dx.doi.org/10.1016/j.euo.2021.03.007DOI Listing
December 2021

Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets.

Pathology 2020 Apr 24;52(3):297-309. Epub 2020 Feb 24.

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Italy; Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Italy. Electronic address:

Recently cabozantinib, a tyrosine kinase inhibitor with activity against VEGF, MET, AXL, and downregulating cathepsin K in vitro, has been proposed for the treatment of advanced clear and non-clear renal cell carcinomas. Since it is well known that cathepsin K is expressed in the majority of MiT family translocation renal cell carcinomas, we investigated cathepsin K, MET, AXL, and VEGF in a large series of those tumours, looking for possible predictive markers. We collected the clinicopathological features of 34 genetically confirmed MiT family translocation renal cell carcinomas [26 Xp11 and 8 t(6;11) renal cell carcinomas] and studied them using an immunohistochemical panel including PAX8, cathepsin K, HMB45, Melan-A, CD68 (PG-M1), CK7, CA9, MET, AXL and by FISH for VEGFA and MET. Cathepsin K was expressed in 14 of 26, HMB45 in 8 of 25, and Melan-A in 4 of 23 Xp11 renal cell carcinomas, whereas labelling for CK7 and CA9 was minimal. In t(6;11) renal cell carcinoma, cathepsin K and melanogenesis markers were constantly positive, whereas CK7 and CA9 were negative. None of the 34 carcinomas showed CD68 (PG-M1) and AXL expression. One aggressive Xp11 renal cell carcinoma showed increased VEGFA gene copy number (4-5 copies) with concurrent gains of TFE3 and TFEB. None of the 34 carcinomas showed MET gene amplification, whereas staining for MET was found in 7 of 8 t(6;11) and in 16 of 24 Xp11 renal cell carcinomas, and in the latter cases, when the expression was >50%, correlated with aggressiveness (p=0.0049). In Xp11 renal cell carcinomas, the aggressiveness was also correlated with larger tumour size (p=0.0008) and the presence of necrosis (p=0.027) but not nucleolar grading (p=1). Interestingly, in patients with tumours exhibiting two of three parameters (necrosis, larger tumour size and MET immunolabelling >50%) an aggressive clinical behaviour was observed in 88% of cases. In conclusion, cathepsin K, CD68 (PG-M1), CK7, CA9, and PAX8 is a useful panel for the diagnosis. Larger tumour size, the presence of necrosis and MET immunohistochemical expression correlate with aggressive behaviour in Xp11 renal cell carcinomas, especially in combination. VEGF, MET, cathepsin K but not AXL may be potential predictive markers for targeted therapy in MiT family translocation renal cell carcinomas.
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http://dx.doi.org/10.1016/j.pathol.2019.11.006DOI Listing
April 2020

Risk of Gleason Score 3+4=7 prostate cancer upgrading at radical prostatectomy is significantly reduced by targeted versus standard biopsy.

Minerva Urol Nefrol 2020 Jun 10;72(3):360-368. Epub 2019 Oct 10.

Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy -

Background: The aim of this study is to evaluate if multiparametric magnetic resonance (mpMRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TBx) versus untargeted standard biopsy (SBx) may decrease the rate of pathological upgrading of Gleason Score (GS) 3+4 prostate cancer (PCa) at radical prostatectomy (RP). We also evaluated the impact of percent pattern 4 and cribriform glands at biopsy in the risk of GS 3+4=7 upgrading.

Methods: A total of 301 patients with GS 3+4 PCa on biopsy (159 SBx and 142 TBx) who underwent laparoscopic robot-assisted RP were sequentially enrolled. Histological data from RP sections were used as reference standard. The concordance of biopsy with pathological GS, as well as the GS 3+4 upgrading at RP were evaluated in different univariate and multivariate binary logistic regression models, testing age, PSA, fPSA%, tumor volume, PI-RADS, clinical stage, percentage of Gleason pattern 4 (GP) and/or presence of cribriform sub-type at biopsy.

Results: Of the 301 biopsies, the median of GP 4 was 16% of the tissue. Minimal GP 4 (≤16%) cancers had a significant lower median volume (1.7 mL) than those with GP4 >16% (2.9 mL), (P<0.001). Pathological GS 3+4 was confirmed for 58.8% and 82.2% for SBx and TBx patients, respectively. The rate of upgraded and downgraded GS on SBx versus TBx was 38.8% vis. 16.7% and 1.8% and 2.1%, respectively. The rate of upgrading was significantly associated with the presence of GP4 >16% versus ≤16% (OR 4.4, 95% CI 1.4-12.0; P=0.021) and with the presence of cribriform sub-type at biopsy specimens (OR 6.2, 95% CI 2.2-18.7; P<0.001).

Conclusions: We demonstrated that TBx technique significantly reduced the risk of GS 3+4 upgrading at RP, compared to SBx one. The rate of upgrading was significantly associated with GP4>16%, mostly when cribriform sub-type was present at biopsy specimens.
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http://dx.doi.org/10.23736/S0393-2249.19.03367-8DOI Listing
June 2020

Prostate cancer management at an Italian tertiary referral center: does multidisciplinary team meeting influence diagnostic and therapeutic decision-making process? A snapshot of the everyday clinical practice.

Minerva Urol Nefrol 2019 Dec 4;71(6):576-582. Epub 2019 Sep 4.

Division of Urology, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

Background: Multidisciplinary team (MDT) management decision-making process appears as an interesting tool to answer most aspects of prostate cancer (PCa) diagnosis and treatment, allowing a fairer choice of therapies. The aim of this study to prospectively investigate the impact on prostate cancer clinical management of the uro-oncology MDT meeting at an Italian tertiary referral center.

Methods: All cases discussed over an 18-months period at San Luigi Hospital uro-oncology MDT were prospectively evaluated for the impact of the MDT discussion on PCa clinical decision-making. Dilemma and management plan in the monodisciplinary visit before and/or after primary treatment were recorded. Subsequently, the MDT discussed the case and reached a consensus decision, which was also recorded. Changes in diagnostic assessment and patient management from pre- to post-MDT meeting were evaluated by a consultant urologist.

Results: Overall, 201 patients, of which 99, 81 and 21 with local, advanced and metastatic disease respectively, were selected for MDT evaluation. The most frequent reasons for MDT approach after either PCa diagnosis or primary treatment were metastatic disease or locally advanced disease/positive surgical margins/biochemical recurrence, respectively. Patients with local, advanced and metastatic disease had a significative change of diagnostic/therapeutic management in 23.2%, 46.9% and 33.4%, respectively (P<0.001). Multimodal treatment was recommended in 25.3%.

Conclusions: The uro-oncology MDT meeting alters management plans in at least one-quarter of patients reaching almost 50% of cases in locally advanced disease.
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http://dx.doi.org/10.23736/S0393-2249.19.03231-4DOI Listing
December 2019

Three-dimensional Elastic Augmented-reality Robot-assisted Radical Prostatectomy Using Hyperaccuracy Three-dimensional Reconstruction Technology: A Step Further in the Identification of Capsular Involvement.

Eur Urol 2019 10 9;76(4):505-514. Epub 2019 Apr 9.

Department of Urology, "San Luigi Gonzaga" Hospital, University of Turin, Orbassano, Turin, Italy.

Background: In prostate cancer (PCa) surgical procedures, in order to maximize potency recovery, a nerve-sparing (NS) procedure is preferred. However, cancer abutting or focally extending beyond the prostate capsule increases the risk of a positive surgical margin.

Objective: To evaluate the accuracy of our new three-dimensional (3D) elastic augmented-reality (AR) system in identifying capsular involvement (CI) location of PCa during the NS phase of robot-assisted radical prostatectomy (RARP). Secondarily, the accuracy of this technology was compared with two-dimensional (2D)-based cognitive procedures.

Design, Setting, And Participants: A prospective study, enrolling 40 patients with PCa undergoing RARP at our center, from May to October 2018.

Surgical Procedure: Patients underwent 3D AR RARP or, in case of unavailability of this technology, 2D cognitive RARP. In all patients, total anatomical reconstruction was used.

Measurements: Clinical data were collected. In order to compare the two groups, nonparametric Mann-Whitney and chi-square tests were performed. A metallic clip was placed at the level of suspicious CI on the basis of images given by the 3D AR or magnetic resonance imaging (MRI) report. The pathological analysis evaluated the presence of tumor at the level of the clip.

Results And Limitations: Twenty patients were enrolled in each group. Focusing on the 3D AR group at macroscopic evaluation, the metallic clip was placed at the tumor and capsular bulging in all cases. At microscopic assessment, cancer presence was confirmed in the suspicious area in 95.4% of the cases. Moreover, CI was correctly identified in 100.0% of the cases, thanks to the 3D image overlap. These results were compared with the 2D MRI cognitive group, showing, at microscopic analysis, statistically significant superiority of the 3D AR group in CI detection during the NS phase (100% vs 47.0%; p<0.05). The main limitation of this technique is that the segmentation and overlapping of the images are performed manually.

Conclusions: Our findings suggest that, with the introduction of the elastic 3D virtual models, prostate deformation is correctly simulated during surgery and lesion location is correctly identified, even in dynamic reality with a subsequent potential reduction of positive surgical margin rate and, in the meantime, maximization of functional outcomes.

Patient Summary: On the basis of our findings, the three-dimensional elastic augmented-reality technology seems to help the surgeon in lesion location identification even in a dynamic phase of the intervention, optimizing the oncological outcomes.
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http://dx.doi.org/10.1016/j.eururo.2019.03.037DOI Listing
October 2019

Radiological Wheeler staging system: a retrospective cohort analysis to improve the local staging of prostate cancer with multiparametric MRI.

Minerva Urol Nefrol 2019 Jun 17;71(3):264-272. Epub 2019 Jan 17.

Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Background: The knowledge of tumor location and extension can allow a modulated radical prostatectomy in order to minimize positive surgical margins and reduce functional morbidity after surgery in patients with prostate cancer (PCa). Multiparametric (mp) magnetic resonance imaging (MRI) could allow the assessment of tumor extension and of its relationship with external structures. Aim of this study is to propose a new radiological Wheeler (rW) staging system applied to mp-MRI, based on the pathologic staging system (pW) for the local assessment of PCa.

Methods: This retrospective single-center multi-reader study included consecutive patients with PCa and preoperative mp-MRI, who underwent non-nerve sparing radical prostatectomy. Three radiologists reported on all examinations and classified each selected lesion according to imaging criteria following rW. Whole-mount histological sections were used as the reference standard. An experienced pathologist classified the extent of prostatic capsular invasion of each PCa according to the pW. Each histological section was scanned for comparison with mp-MRI findings. The rate of PCa correctly classified by radiologists using the pW was assessed. To evaluate the accuracy of mp-MRI in the discrimination between T2 and T3 PCa, the AUC was computed.

Results: One-hundred and five patients with a total of 195 PCa foci were included in the study. 130/195 tumors with a clear overlap between mp-MRI and surgical specimens were selected. The sensitivity of the most experienced reader was lower than that of the other two readers (48.6% vs. 68.6% and 62.9%, P>0.09) while specificity and PPV were higher (95.8% vs. 79.0% and 57.9%, P<0.001; 81.0% vs. 54.6% and 35.5%, P<0.041; respectively). The AUC values for the most and the intermediate experienced readers in the detection of extracapsular extension were in the range 0.72-0.74.

Conclusions: The rW staging system has low accuracy in predicting each single pW class, while accuracy was over 80% for experienced readers in the identification of organ-confined (T2 stage class) tumors and non-organ confined cases (T3 stage class).
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http://dx.doi.org/10.23736/S0393-2249.19.03248-XDOI Listing
June 2019

Low-dose radiotherapy for extranodal marginal zone B lymphoma of the lip: Case report and literature review.

Hematol Oncol Stem Cell Ther 2021 Mar 31;14(1):76-81. Epub 2018 Dec 31.

Department of Radiation Oncology, University of Turin School of Medicine, Mauriziano Umberto I Hospital, Turin, Italy. Electronic address:

Non-Hodgkin lymphoma (NHL) of the lip is extremely rare. It is usually indolent and in early stages a local approach is often indicated. We present a case report of a patient with extranodal NHL of the lip treated with chemotherapy and low-dose radiation treatment (RT). The patient was affected by B-cell NHL of the marginal zone, Stage IAE. After a few months of observation with progressive disease, the patient was submitted to two cycles of chemotherapy with no response. Therefore, he was treated with very low-dose RT consisting of two fractions of 2 Gy. Complete response was observed and after 1-year follow-up, persistent complete response was recorded. In cases of localized disease, especially in patients with comorbidities of poor performance status (PS), low-dose RT can be an appropriate approach with excellent outcomes in terms of effectiveness and low risk of toxicity.
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http://dx.doi.org/10.1016/j.hemonc.2018.12.002DOI Listing
March 2021

The role of side-specific biopsy and dominant tumor location at radical prostatectomy in predicting the side of nodal metastases in organ confined prostate cancer: is lymphatic spread really unpredictable?

Minerva Urol Nefrol 2019 Apr 7;71(2):146-153. Epub 2018 Nov 7.

Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy -

Background: The aim of this study was to evaluate the correlation between the location of prostate cancer (PCa) either at biopsy or at radical prostatectomy (RP) specimens and the side of positive lymph nodes (LNs). Furthermore, we assessed the risk of contralateral LN metastasis (LNMs) in patients with unilateral positive biopsy and/or dominant lesion at RP.

Methods: We reviewed retrospectively our prospectively maintained database of patients with LNM treated with robot-assisted RP and bilateral robot-assisted extended pelvic lymph node dissection (EPLND) for PCa from January 2014 to May 2018 at a surgical high-volume center. All men with a suspicion for PCa underwent a 12-cores prostate biopsy. In case of a first negative biopsy but the persistence of suspicion, all the patients underwent prostate multiparametric magnetic resonance imaging (mpMRI) and subsequently either fusion targeted biopsy (TBx) or systematic standard biopsy (SBx), in case of positive or negative mpMRI, respectively. All patients underwent a robot-assisted RP. Whole-mount histological sections resected from the RP specimens were used as reference standards.

Results: Eighty-seven patients were enrolled for the study. Median number of LNs retrieved per patient was 26, specifically 13 and 12, on the left and right side, respectively. Seven of 24 (29.1%) right lobe positive biopsy showed positive LNs on the left side (one exclusively left, 6 bilateral LNMs). Again, 12 of 26 (46.1%) left lobe positive biopsy showed positive LNs on the right side (one exclusively right, 11 bilateral LNMs). No significant differences of performance to predict the side of LNMs were recorded in the SBx and TBx groups. Concerning RP specimens, only five of 22 (22.7%) right lobe dominant cases showed positive LNs on the left side (two exclusively left, 3 bilateral LN metastases). Again, none of 16 left lobe dominant cases showed positive LNs on the contralateral side (15 exclusively right, 1 bilateral LNMs).

Conclusions: Our results suggest confirmed that a unilateral LN dissection limited to the tumor-bearing side of the gland evaluated by biopsy specimens should not be recommended due to the substantial risk of missing contralateral LNMs.
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http://dx.doi.org/10.23736/S0393-2249.18.03286-1DOI Listing
April 2019

Augmented-reality robot-assisted radical prostatectomy using hyper-accuracy three-dimensional reconstruction (HA3D™) technology: a radiological and pathological study.

BJU Int 2019 05 19;123(5):834-845. Epub 2018 Oct 19.

Department of Urology, 'San Luigi Gonzaga' Hospital, Orbassano (Turin), Italy.

Objectives: To assess the use of hyper-accuracy three-dimensional (HA3D™; MEDICS, Moncalieri, Turin, Italy) reconstruction based on multiparametric magnetic resonance imaging (mpMRI) and superimposed imaging during augmented-reality robot-assisted radical prostatectomy (AR-RARP).

Patients And Methods: Patients with prostate cancer (clinical stages cT1-3, cN0, cM0) undergoing RARP at our Centre, from June 2017 to April 2018, were enrolled. In all cases, cancer was diagnosed with targeted biopsy at the level of index lesion based on high-resolution (1-mm slices) mpMRI. HA3D reconstruction was created by dedicated software to obtain the 3D virtual model of the prostate and surrounding structures. A specific system was used to overlay virtual data on the endoscopic video displayed by the remote da Vinci® surgical console (Intuitive Surgical Inc., Sunnyvale, CA, USA), and the virtual images were superimposed by the surgeon by the means of the TilePro™ multi-input display technology (Intuitive Surgical Inc.). The AR technology was used in four standardised key steps during RARP. The procedures were modulated differently in cases of prostate cancer without extracapsular extension (ECE) at mpMRI (Group A) or in cases of prostate cancer with ECE (Group B) at mpMRI. In Group A, the virtual image of the prostate was overlaid on the endoscopic view and the intraprostatic lesion was marked on the prostate surface by a metallic clip at the level of the suspicious lesion as identified by the 3D virtual AR image. In Group B, the same step was performed; moreover, a metallic clip was placed at the level of the suspicious ECE on the neurovascular bundles (NVBs) according to the virtual images. Finally, selective biopsies were taken from the NVBs at this level, and then, the entire NVBs were removed for final pathological examination, according to standard clinical indications. For Group A, the pathologist performed a targeted needle biopsy at the level of the metallic clip on the surface of prostate before the sample reduction. For Group B, the presence of tumour was evaluated during the reduction phase, at the level of metallic clip on the prostate surface and at the level of NVBs, sent separately. Finally, an image 3D scanner (Kinect, Microsoft) was used to perform a dimensional comparison between the mpMRI-based 3D virtual reconstruction and the whole-mount specimen.

Results: In all, 30 patients were enrolled in the present study, 11 (36.6%) included in Group A and 19 (63.4%) in Group B. In all cases (30/30), final pathology confirmed the location of the index lesion, as cancer was found at the level of the metallic clip. The suspected ECE was confirmed on final pathology in 15/19 cases (79%). The AR-guided selective biopsies at the level of the NVBs confirmed the ECE location, with 11/15 (73.3%) biopsies at the level of NVBs positive for cancer. The mismatch between the 3D virtual reconstruction and the prostate 3D scanning based on the whole-mount specimen was <3 mm in >85% of the gland.

Conclusion: Our results suggest that a HA3D virtual reconstruction of the prostate based on mpMRI data and real-time superimposed imaging allow performance of an effective AR-RARP. Potentially, this approach translates into better outcomes, as the surgeon can tailor the procedure for each patient.
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http://dx.doi.org/10.1111/bju.14549DOI Listing
May 2019

Metastatic Renal Medullary Carcinoma Treated With Immune Checkpoint Inhibitor: Case Report and Literature Review.

Clin Genitourin Cancer 2018 12 21;16(6):e1087-e1090. Epub 2018 Jul 21.

Department of Oncology, Division of Medical Oncology, San Luigi Gonzaga Hospital, University of Turin, Turin, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2018.07.011DOI Listing
December 2018

Tissue-based multigene expression tests for pretreatment prostate cancer risk assessment: current status and future perspectives.

Future Oncol 2018 Dec 15;14(29):3073-3083. Epub 2018 Aug 15.

Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, USA.

Prostate cancer is a highly prevalent disease with ample spectrum of aggressiveness and treatment options. Low-risk disease can be safely managed by nonintervention strategies, such as active surveillance; however, accurate risk assessment is warranted. Molecular tests have been developed and validated to complement standard clinicopathological parameters and help to improve risk stratification in prostate cancer. Herein, we review selected tissue-based assays, including genomic prostate score, cell cycle progression score and genomic classifier, with particular emphasis on their role in patient risk assessment in a pretreatment setting, in view of their current or potential utilization in active surveillance.
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http://dx.doi.org/10.2217/fon-2018-0287DOI Listing
December 2018

Human renal angiomyolipoma cells of male and female origin can migrate and are influenced by microenvironmental factors.

PLoS One 2018 19;13(6):e0199371. Epub 2018 Jun 19.

Department of Clinical and Biological Science, University of Turin, Orbassano, Italy.

Background: Improving the knowledge of angiomyolipoma physiopathology might help in refining its pharmacological treatment. We investigated if angiomyolipoma cells have migratory properties, how their growth and motility can be influenced by the hormonal milieu, and if this can be related to a specific gender.

Methods: Primary cells were isolated from angiomyolipomas surgically resected for therapeutical reasons in a female and in a male patient. The genetic control demonstrated no TSC2 deletion. Bi- (wound healing) and three-dimensional (transwell assay) migration were analyzed in vitro in basal conditions and under the influence of 17- β-estradiol and SDF-1α.

Results: Treatment up to 72 hours with 17-β-estradiol (0.1-100 nM), tamoxifen (0.2-20 μM) or with both, does not modify angiomyolipoma cells proliferation. On the other hand, SDF-1α and 17-β-estradiol treatment induce a significant motility increase (both bi- and three-dimensional) which becomes evident already after 2 hours of incubation. Angiomyolipoma cells express mRNA coding for SDF-1α and 17-β-estradiol receptors and secrete both the metalloproteases principally involved in malignant phenotype acquisition, i.e. MMP-2 and MMP-9.

Conclusion: Angiomyolipoma cells behave similarly, despite their different source. Primary angiomyolipoma cells migrate in response to hormonal milieu and soluble factors, and produce active metalloproteases, both aspects being consistent with the theory claiming they can migrate to the lungs (and/or other organs) and colonizing them. No main feature, among the aspects we analyzed, seems to be referable to the gender of origin.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199371PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007918PMC
April 2019

Comparing Image-guided targeted Biopsies to Radical Prostatectomy Specimens for Accurate Characterization of the Index Tumor in Prostate Cancer.

Anticancer Res 2018 05;38(5):3043-3047

Division of Urology, San Luigi Gonzaga Hospital and University of Turin, Orbassano, Italy.

Aim: To evaluate the accuracy of multiparametric magnetic resonance-transrectal ultrasound fusion targeted biopsy (TBx) in the characterization of the index tumor, as confirmed by association with radical prostatectomy (RP) specimens.

Patients And Methods: A total of 152 patients with TBx-confirmed prostate cancer (PCa) underwent robot-assisted RP. Stained whole-mount histological sections were used as the reference standard. All lesions with a volume >0.5 ml and/or pathological Gleason score (GS) >6 were defined as clinically significant PCa. The index lesion was defined as the largest tumor focus within the prostate gland.

Results: The pathological index tumours included: 147 lesions (96.7%) with a volume >0.5 ml and five (3.3%) with a volume ≤0.5 ml, but with a pathological GS ≥7; 135 (88.8%) were located in the peripheral zone. TBx accuracy in the detection of the correct site of the index lesion by reference standard was 82.2%. Sensitivity, specificity, positive and negative predictive value were: 82.3%, 50.4%, 82.8% and 49.7%, respectively. The primary/secondary Gleason grade and GS of the 152 index tumors were properly estimated in 130 (85.5%), 115 (75.6%) and 127 (83.6%) cases, respectively. The concordance of TBx with pathological GS was 83.6%. The rate of up-grading and down-grading of TBx Gleason sum was 12.2% and 4.2%, respectively.

Conclusion: TBx has a high sensitivity for characterization of index lesions, with a good concordance for topographic and Gleason grading accuracy between biopsy and surgical specimens.
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http://dx.doi.org/10.21873/anticanres.12560DOI Listing
May 2018

Indication to pelvic lymph nodes dissection for prostate cancer: the role of multiparametric magnetic resonance imaging when the risk of lymph nodes invasion according to Briganti updated nomogram is <5.

Prostate Cancer Prostatic Dis 2018 04 22;21(1):85-91. Epub 2018 Feb 22.

Division of Urology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, TO, Italy.

Background: The Briganti updated nomogram (BN) is the most popular predictive model aiming to predict the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa), but it lacks information obtained by preoperative imaging. The primary aim of the study was to evaluate the role of multiparametric prostate magnetic resonance imaging (mp-MRI) in the indication to perform pelvic lymph nodes dissection (PLND) or not in patients with risk of LNI according to BN below 5%.

Methods: Since March 2012 and September 2016, 310 patients who underwent a preoperative mp-MRI for staging purpose and subsequent robot-assisted extended PLND (RAEPLND) were retrospectively evaluated. Mp-MRIs were prospectively analyzed by two experienced radiologists. The imaging parameters analyzed were the presence of extracapsular extension (ECE), seminal vesicles invasion (SVI) and predominant Gleason pattern 4 (pG4). All patients underwent RAEPLND by two experienced surgeons with a standardized technique. A dedicated uropathologist performed all pathological analysis. Univariate analysis and multivariate logistic regression analysis were used in order to identify the predictors of LNI in patients with PCa.

Results: In the overall population, 57 (18.4%) patients had histologically proven pN1 disease. 48/250 patients (19.2%) with a risk of LNI ≥5% as calculated by the BN were staged pN1 at final histopathological analysis. 9/60 patients (15.0%) with a risk of LNI <5% as calculated by BN, who underwent RAEPLND anyway according to the findings at mp-MRI, were staged pN1 at final histopathological analysis. At multivariate logistic regression analysis, all the three mp-MRI parameters were significant independent predictors of LNI after RAEPLND.

Conclusions: The role of mp-MRI seemed to be crucial in patients with a risk of LNI <5% as calculated by the BN. The presence of ECE, SVI, or pG4 at mp-MRI was found to be an independent predictor of LNI by itself.
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http://dx.doi.org/10.1038/s41391-017-0026-5DOI Listing
April 2018

Interpathologist concordance in the histological diagnosis of focal prostatic atrophy lesions, acute and chronic prostatitis, PIN, and prostate cancer.

Virchows Arch 2017 Jun 12;470(6):711-715. Epub 2017 Apr 12.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 677 Avenue, Huntington, MA, 02115, USA.

Epidemiological and biological evidence indicates a causal relationship between the presence of proliferative atrophic lesions and the development of prostatic intraepithelial neoplasia (PIN) and prostate cancer. The presence of inflammatory and atrophic lesions of the prostate is widely underestimated and they are not generally mentioned in pathology reports. We performed a histopathological concordance study among eight genitourinary specialists and seven generalist pathologists, using 116 histological slides of prostate lesions, including proliferative atrophic lesions, PIN, and cancer. The overall agreement between all possible pairs of reviewers was 80% for prostate cancer, 67% for PIN, and 49% for proliferative atrophic lesions. When using as gold standard the assessment of a single genitourinary pathologist, the mean agreement percentage increased to 97% for prostate cancer, 92% for PIN, and 72% for proliferative atrophic lesions.
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http://dx.doi.org/10.1007/s00428-017-2123-1DOI Listing
June 2017

Multiparametric Magnetic Resonance/Ultrasound Fusion Prostate Biopsy: Number and Spatial Distribution of Cores for Better Index Tumor Detection and Characterization.

J Urol 2017 07 16;198(1):58-64. Epub 2017 Jan 16.

Division of Urology, San Luigi Gonzaga Hospital and University of Turin, Orbassano, Italy.

Purpose: We evaluated the minimum core number for better index tumor detection to determine the best core site as well as biopsy Gleason score heterogeneity in the same index lesion. The aim was to optimize the highest Gleason score detection.

Materials And Methods: A total of 327 patients with negative digital rectal examination underwent magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy for elevated/rising prostate specific antigen and/or 1 or more detectable lesions on multiparametric magnetic resonance imaging after a previous negative standard biopsy. Depending on the diameter of each index lesion (8 or less, or greater than 8 mm) 4 or 6 cores, respectively, were taken according to a well determined sequence.

Results: Of the patients 166 (50.7%) had prostate cancer, including 79 (47.6%) with an 8 mm or less index lesion and 87 (52.4%) with a greater than 8 mm index lesion. Of patients with an index tumor 8 mm or less 7 (8.9%) had 1, 31 (39.2%) had 2, 27 (34.2%) had 3 and 14 (17.7%) had 4 positive cores. Similarly, of patients with a lesion greater than 8 mm 8 (9.2%) had 1, 30 (34.5%) had 2, 13 (14.9%) had 3, 14 (16.1%) had 4, 12 (13.8%) had 5 and 10 (11.5%) had 6 positive cores. The major prevalence of positive cores was observed in the center of the target. Gleason score heterogeneity was found in 12.6% of those with an 8 mm or less target vs 26.4% with a target greater than 8 mm. In the center of the target there was a slight prevalence of Gleason pattern 4 or greater, or a lesser pattern.

Conclusions: Approaching magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy with a single core might be inadequate. Rather, taking 2 cores in the center of the index lesion may provide more accurate cancer detection and optimize the chances of finding the highest Gleason pattern.
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http://dx.doi.org/10.1016/j.juro.2017.01.036DOI Listing
July 2017

T1 high-grade bladder carcinoma outcome: the role of p16, topoisomerase-IIα, survivin, and E-cadherin.

Hum Pathol 2016 11 26;57:78-84. Epub 2016 Jul 26.

Unit of Anatomical Pathology, Department of Surgery, Faculty of Medicine, Cordoba, Spain; Champalimaud Clinical Center, Lisbon, Portugal.

High-grade papillary urothelial carcinoma with subepithelial connective tissue invasion (T1HG) is an aggressive disease at high risk of progression after transurethral resection/Bacillus Calmette-Guerin standardized therapy. The European Organization for Research and Treatment of Cancer has identified T1HG bladder carcinoma that is single and ≤3 cm in the largest dimension at first diagnosis as a category in which the prognosis cannot be further stratified based on conventional criteria. This category may benefit from biomarker analysis as a valuable tool to determine the patient's outcome. To further the issue of biomarkers in predicting aggressiveness in single T1HG bladder carcinoma ≤3 cm in greatest dimension at first diagnosis, we have conducted a validation study of the biomarker risk score set previously reported by our group. The study set included immunohistochemical detection of galectin-3, CD44, E-cadherin (E-CAD), CD138, p16, survivin, HYAL-1, and topoisomerase-IIα in 92 randomly selected specimens at participating institutions. Topoisomerase-IIα expression was identified as a predictor of disease-free survival. p16, survivin, and E-CAD expression predicted progression-free survival, but p16 and E-CAD also predicted overall survival. The current study validates a panel of immunohistochemical markers with the potential of being implemented in practice and supports the use of biomarkers in predicting aggressiveness in patients with first diagnosis of single T1HG bladder carcinoma ≤3 cm in greatest dimension and therefore in identifying patients who need closer surveillance or earlier aggressive treatment.
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http://dx.doi.org/10.1016/j.humpath.2016.06.022DOI Listing
November 2016

High prostate cancer gene 3 (PCA3) scores are associated with elevated Prostate Imaging Reporting and Data System (PI-RADS) grade and biopsy Gleason score, at magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy after a previous negative standard biopsy.

BJU Int 2016 Nov 24;118(5):723-730. Epub 2016 May 24.

Department of Urology, San Luigi Gonzaga Hospital, University of Torino, Orbassano, Italy.

Objective: To determine the association among prostate cancer gene 3 (PCA3) score, Prostate Imaging Reporting and Data System (PI-RADS) grade and Gleason score, in a cohort of patients with elevated prostate-specific antigen (PSA), undergoing magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy (TBx) after a previous negative randomised 'standard' biopsy (SBx).

Patients And Methods: In all, 282 patients who underwent TBx after previous negative SBx and a PCA3 urine assay, were enrolled. The associations between PCA3 score/PI-RADS and PCA3 score/Gleason score were investigated by K-means clustering, a receiver operating characteristic analysis and binary logistic regression.

Results: The PCA3 score difference for the negative vs positive TBx cohorts was highly statistically significant. A 1-unit increase in the PCA3 score was associated to a 2.4% increased risk of having a positive TBx result. A PCA3 score of >80 and a PI-RADS grade of ≥4 were independent predictors of a positive TBx. The association between the PCA3 score and PI-RADS grade was statistically significant (the median PCA3 score for PI-RADS grade groups 3, 4, and 5 was 58, 104, and 146, respectively; P = 0.006). A similar pattern was detected for the relationship between the PCA3 score and Gleason score; an increasing PCA3 score was associated with a worsening Gleason score (median PCA3 score equal to 62, 105, 132, 153, 203, and 322 for Gleason Score 3+4, 4+3, 4+4, 4+5, 5+4, and 5+5, respectively; P < 0.001).

Conclusion: TBx improved PCA3 score diagnostic and prognostic performance for prostate cancer. The PCA3 score was directly associated both with biopsy Gleason score and PI-RADS grade: notably, in the 'indeterminate' PI-RADS grade 3 subgroup.
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http://dx.doi.org/10.1111/bju.13504DOI Listing
November 2016

Multiparametric-Magnetic Resonance/Ultrasound Fusion Targeted Prostate Biopsy Improves Agreement Between Biopsy and Radical Prostatectomy Gleason Score.

Anticancer Res 2016 09;36(9):4833-9

Division of Radiology, San Luigi Gonzaga Hospital Orbassano and University of Torino-I, Turin, Italy.

Aim: To investigate if targeted prostate biopsy (TBx) has superior performance to standard untargeted biopsy (SBx) in determining the optimal agreement between biopsy and surgical Gleason Score (GS).

Patients And Methods: An analysis of our institutional longitudinal database identified 683 consecutive patients who underwent either SBx (18-20 standardized transrectal ultrasound peripheral/transitional zone cores) or TBx alone (4-6 cores for each multiparametric magnetic resonance suspicious lesion, Prostate Imaging Reporting and Data System [(PI-RADS)≥3] after a previous negative first SBx. A total of 246 consecutive patients with diagnosis of prostate cancer (117 SBx and 129 TBx diagnoses) who underwent robot-assisted radical prostatectomy between January 2014 and December 2015, were enrolled. The concordance of biopsy GS to pathological GS, as well as the association between categorical variables [age, digital rectal exam (DRE), TNM, PI-RADS], were analyzed by Fisher's exact test.

Results: Prostate cancer was diagnosed in 32.0% of the SBx group and in 49.3% of TBx. The rate of correctly classified, up-graded and down-graded GS was 53.8% vs. 91.5%, 39.3% vs. 7.8% and 6.8% vs. 0.8% for SBx and TBx, respectively (p<0.001). The GS concordance rates for SBx and TBx cohorts were: 14.3% vs. 41.7% for GS 6, 61.0% vs. 83.8% for GS 3+4, 56.3% vs. 75.0% for GS 4+3, 27.3% vs. 100% for GS 8 and 80% vs. 100% for GS 9, respectively.

Conclusion: TBx ensured a higher of accuracy of prostate cancer detection and a better performance in discriminating significant from insignificant prostate cancer, when compared to SBx. TBx significantly reduced the risk of GS up-/down-grading at radical prostatectomy for all histopathological categories. This is a notable advance in the selection of candidates for active surveillance.
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http://dx.doi.org/10.21873/anticanres.11045DOI Listing
September 2016

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer.

Eur Urol 2017 08 27;72(2):282-288. Epub 2016 Aug 27.

Division of Urology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

Background: An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa).

Objective: To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa.

Design, Setting, And Participants: Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105).

Intervention: In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB.

Outcomes Measurements And Statistical Analysis: The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB.

Results And Limitations: The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature.

Conclusions: A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa.

Patient Summary: In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway.
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http://dx.doi.org/10.1016/j.eururo.2016.08.041DOI Listing
August 2017

Androgen deprivation modulates gene expression profile along prostate cancer progression.

Hum Pathol 2016 10 21;56:81-8. Epub 2016 Jun 21.

Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address:

Androgen deprivation therapy (ADT) is the standard of care for metastatic prostate cancer and initially induces tumor regression, but invariably results in castration-resistant prostate cancer through various mechanisms, incompletely discovered. Our aim was to analyze the dynamic modulation, determined by ADT, of the expression of selected genes involved in the pathogenesis and progression of prostate cancer (TMPRSS2:ERG, WNT11, SPINK1, CHGA, AR, and SPDEF) using real-time polymerase chain reaction in a series of 59 surgical samples of prostate carcinomas, including 37 cases preoperatively treated with ADT and 22 untreated cases, and in 43 corresponding biopsies. The same genes were analyzed in androgen-deprived and control LNCaP cells. Three genes were significantly up-modulated (WNT11 and AR) or down-modulated (SPDEF) in patients treated with ADT versus untreated cases, as well as in androgen-deprived LNCaP cells. The effect of ADT on CHGA gene up-modulation was almost exclusively detected in cases positive for the TMPRSS2:ERG fusion. The correlation between biopsy and surgical samples was poor for most of the tested genes. Gene expression analysis of separate tumor areas from the same patient showed an extremely heterogeneous profile in the 6 tested cases (all untreated). In conclusion, our results strengthened the implication of ADT in promoting a prostate cancer aggressive phenotype and identified potential biomarkers, with special reference to the TMPRSS2:ERG fusion, which might favor the development of neuroendocrine differentiation in hormone-treated patients. However, intratumoral heterogeneity limits the use of gene expression analysis as a potential prognostic or predictive biomarker in patients treated with ADT.
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http://dx.doi.org/10.1016/j.humpath.2016.06.004DOI Listing
October 2016

Multiparametric magnetic resonance imaging and active surveillance: How to better select insignificant prostate cancer?

Int J Urol 2016 09 9;23(9):752-7. Epub 2016 Jun 9.

Division of Radiology, Institute for Cancer Research and Treatment, Turin, Italy.

Objectives: To evaluate the role of multiparametric magnetic resonance imaging in improving the predictive accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria for active surveillance in prostate cancer.

Methods: A retrospective study was carried out with 126 prostate cancer patients treated with robot-assisted radical prostatectomy, but eligible for active surveillance according to the Prostate Cancer Research International: Active Surveillance criteria; 63 patients were also eligible according to the Epstein criteria. All patients underwent preoperative multiparametric magnetic resonance imaging, after at least 6 weeks from biopsy. The images from the multiparametric magnetic resonance imaging were assessed, and diagrams showing prostate sextants were used to designate regions of abnormalities within the prostate. Findings in the prostate were assigned to one of five categories according the Prostate Imaging-Reporting and Data System guidelines (v1.0), and considered positive for prostate cancer if the final Prostate Imaging-Reporting and Data System guidelines were >3 and negative if ≤3. Multivariate logistic regression analysis was carried out to evaluate the gain in accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria when added to multiparametric magnetic resonance imaging. Decision curve analysis was carried out to identify the net benefit of each model.

Results: The inclusion of multiparametric magnetic resonance imaging to the Epstein criteria and the Prostate Cancer Research International: Active Surveillance multivariate model significantly increased their accuracy in predicting pathologically-confirmed insignificant prostate cancer by 7% and 5%, respectively. At the decision curve analysis evaluation, the model including the Prostate Cancer Research International: Active Surveillance criteria and multiparametric magnetic resonance imaging improved the clinical risk prediction over the other models.

Conclusions: The present findings suggest that multiparametric magnetic resonance imaging is able to increase the predictive accuracy of Prostate Cancer Research International: Active Surveillance and Epstein criteria to identify prostate cancer patients eligible for active surveillance.
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http://dx.doi.org/10.1111/iju.13138DOI Listing
September 2016

Renal oncocytosis: a clinicopathological and cytogenetic study of 42 tumours occurring in 11 patients.

Pathology 2016 Jan 18;48(1):41-6. Epub 2015 Dec 18.

Division of Pathology of the University of Turin at San Luigi Hospital, Orbassano, Turin, Italy.

Renal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from renal oncocytoma, hybrid oncocytic tumour and rarely chromophobe renal cell carcinoma, sometimes overlapping. Here we retrospectively analysed histological, immunohistochemical (IHC), and cytogenetic features of 42 lesions in 11 patients with renal oncocytosis, not associated with Birt-Hogg-Dubé syndrome. The histology of all the lesions was blindly reviewed by three dedicated genitourinary pathologists. IHC for cytokeratin 7 (CK7) and fluorescence in situ hybridisation (FISH) for copy number variation of chromosomes 1, 6, 7 and 17 were performed in all 42 nodules. Among the 42 lesions 36 (85.7%) were histologically renal oncocytomas, two (4.76%) 'hybrid oncocytic tumours' (HOT), one (2.4%) clear cell renal cell carcinoma (ccRCC), one (2.4%) papillary renal cell carcinoma (pRCC), one typical angiomyolipoma (2.4%), and one mixed epithelial/stromal tumour of the kidney (2.4%). FISH analysis confirmed the histological diagnosis of all the lesions. We show that most patients with renal oncocytosis harbour benign or low malignant potential tumours that can be treated conservatively.
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http://dx.doi.org/10.1016/j.pathol.2015.11.009DOI Listing
January 2016

Retrospective study testing next generation sequencing of selected cancer-associated genes in resected prostate cancer.

Oncotarget 2016 Mar;7(12):14394-404

University of Turin, Department of Oncology, Orbassano, Italy.

Purpose: Prostate cancer (PCa) has a highly heterogeneous outcome. Beyond Gleason Score, Prostate Serum Antigen and tumor stage, nowadays there are no biological prognostic factors to discriminate between indolent and aggressive tumors.The most common known genomic alterations are the TMPRSS-ETS translocation and mutations in the PI3K, MAPK pathways and in p53, RB and c-MYC genes.The aim of this retrospective study was to identify by next generation sequencing the most frequent genetic variations (GVs) in localized and locally advanced PCa underwent prostatectomy and to investigate their correlation with clinical-pathological variables and disease progression.

Results: Identified non-synonymous GVs included TP53 p.P72R (78% of tumors), two CSFR1 SNPs, rs2066934 and rs2066933 (70%), KDR p.Q472H (67%), KIT p.M541L (28%), PIK3CA p.I391M (19%), MET p.V378I (10%) and FGFR3 p.F384L/p.F386L (8%). TP53 p.P72R, MET p.V378I and CSFR1 SNPs were significantly associated with the HI risk group, TP53 and MET variations with T≥T2c. FGFR3 p.F384L/p.F386L was correlated with T≤T2b. MET p.V378I mutation, detected in 20% of HI risk patients, was associated with early biochemical recurrence.

Experimental Design: Nucleic acids were obtained from tissue samples of 30 high (HI) and 30 low-intermediate (LM) risk patients, according to D'Amico criteria. Genomic DNA was explored with the Ion_AmpliSeq_Cancer_Hotspot_Panel_v.2 including 50 cancer-associated genes. GVs with allelic frequency (AF) ≥10%, affecting protein function or previously associated with cancer, were correlated with clinical-pathological variables.

Conclusion: Our results confirm a complex mutational profile in PCa, supporting the involvement of TP53, MET, FGFR3, CSF1R GVs in tumor progression and aggressiveness.
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http://dx.doi.org/10.18632/oncotarget.7343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924723PMC
March 2016

Pitfalls in the diagnosis of adrenocortical tumors: a lesson from 300 consultation cases.

Hum Pathol 2015 Dec 11;46(12):1799-807. Epub 2015 Sep 11.

Department of Oncology, University of Turin at San Luigi Hospital, Orbassano 10043, Turin, Italy. Electronic address:

The correct pathologic classification of adrenocortical carcinoma (ACC) is relevant to establish an early therapeutic strategy of this rare malignancy. The aim of the study was to assess the most frequent pitfalls in ACC diagnosis reviewing a large consecutive series of 300 cases with an original diagnosis or a clinical suspect of ACC, which were sent in consultation to our institution between 2004 and 2014. A major disagreement that significantly modified the clinical management of patients was recorded in 26 cases (9%). The most common pitfall (10 cases) was to distinguish ACC from pheochromocytoma and vice versa. Seven other cases diagnosed as ACC were reclassified as metastases from other primaries and primary adrenal soft tissue tumors (including 3 angiosarcomas). Finally, 5 adrenocortical adenomas were reclassified into carcinomas, and 4 ACCs were converted into adenomas. Minor disagreements were mostly related to the identification of ACC variants (up to 32% of cases of adrenocortical tumors in the present series). Moreover, more than 50% of ACC cases lacked Ki-67. In conclusion, our results indicate that, in the presence of a histologically suspected ACC, a special attention should be devoted to exclude metastatic and soft tissue tumors and pheochromocytoma (in this latter case with special reference to the oncocytic variant of adrenocortical tumors). Moreover, pathologists should be aware of the major role of Ki-67 in determining prognosis and in selecting patients to the most appropriate treatment.
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http://dx.doi.org/10.1016/j.humpath.2015.08.012DOI Listing
December 2015
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