Publications by authors named "Gian Luca Rampioni Vinciguerra"

17 Publications

  • Page 1 of 1

CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer.

J Pathol 2021 Feb 4;253(2):234-245. Epub 2020 Dec 4.

Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO Aviano), IRCCS, National Cancer Institute, Aviano, Italy.

The CDKN1B gene, encoding for the CDK inhibitor p27 , is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra-deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor-positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell-free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27 protein truncation, leading to loss of most of the protein or of its C-terminal domain. Using a gene-editing approach in a luminal breast cancer cell line, MCF-7, we observed that the expression of p27 truncating mutants that lose the C-terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C-terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839435PMC
February 2021

Downregulation of miR-223 Expression Is an Early Event during Mammary Transformation and Confers Resistance to CDK4/6 Inhibitors in Luminal Breast Cancer.

Cancer Res 2020 03 20;80(5):1064-1077. Epub 2019 Dec 20.

Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Aviano, Italy.

miR-223 is an anti-inflammatory miRNA that in cancer acts either as an oncosuppressor or oncopromoter, in a context-dependent manner. In breast cancer, we demonstrated that it dampens the activation of the EGF pathway. However, little is known on the role of miR-223 during breast cancer onset and progression. miR-223 expression was decreased in breast cancer of luminal and HER2 subtypes and inversely correlated with patients' prognosis. In normal luminal mammary epithelial cells, miR-223 acted cell autonomously in the control of their growth and morphology in three-dimensional context. In the MMTV-Δ16HER2 transgenic mouse model, oncogene transformation resulted in a timely abrogation of miR-223 expression, likely due to activation of E2F1, a known repressor of miR-223 transcription. Accordingly, treatment with CDK4/6 inhibitors, which eventually results in restraining E2F1 activity, restored miR-223 expression and miR-223 ablation induced luminal breast cancer resistance to CDK4/6 inhibition, both and . Notably, miR-223 expression was lost in microdissected ductal carcinoma (DCIS) from patients with luminal and HER2-positive breast cancer. Altogether, these results identify downmodulation of miR-223 as an early step in luminal breast cancer onset and suggest that it could be used to identify aggressive DCIS and predict the response to targeted therapy. SIGNIFICANCE: miR-223 may represent a predictive biomarker of response to CDK4/6 inhibitors and its loss could identify DCIS lesions that are likely to progress into invasive breast cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-1793DOI Listing
March 2020

TIMP-1 is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells.

Cells 2019 12 18;9(1). Epub 2019 Dec 18.

Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

Epithelial Ovarian Cancer (EOC) is the most lethal gynecological cancer in developed countries, and the development of new strategies to overcome chemoresistance is an awaited clinical need. Angiogenesis, the development of new blood vessels from pre-existing vasculature, has been validated as a therapeutic target in this tumor type. The aim of this study is to verify if EOC cells with acquired resistance to platinum (PT) treatment display an altered angiogenic potential. Using a proteomic approach, we identified the tissue inhibitor of metalloproteinases 1 (TIMP-1) as the only secreted factor whose expression was up-regulated in PT-resistant TOV-112D and OVSAHO EOC cells used as study models. We report that TIMP-1 acts as a double-edged sword in the EOC microenvironment, directly affecting the response to PT treatment on tumor cells and indirectly altering migration and proliferation of endothelial cells. Interestingly, we found that high TIMP-1 levels in stage III-IV EOC patients associate with decreased overall survival, especially if they were treated with PT or bevacizumab. Taken together, these results pinpoint TIMP-1 as a key molecule involved in the regulation of EOC PT-resistance and progression disclosing the possibility that it could be used as a new biomarker of PT-resistance and/or therapeutic target.
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http://dx.doi.org/10.3390/cells9010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016675PMC
December 2019

Sleeping beauty genetic screen identifies miR-23b::BTBD7 gene interaction as crucial for colorectal cancer metastasis.

EBioMedicine 2019 Aug 11;46:79-93. Epub 2019 Jul 11.

Division of Molecular Oncology, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Italy.

Background: Metastatic colorectal cancer (CRC) remains a deadly disease. Identifying locally advanced CRC patients with high risk of developing metastasis and improving outcome of metastatic CRC patients require discovering master regulators of metastasis. In this context, the non-coding part of the human genome is still largely unexplored.

Methods: To interrogate the non-coding part of the human genome and disclose regulators of CRC metastasis, we combined a transposon-based forward genetic screen with a novel in vitro assay, which forces cells to grow deprived of cell-substrate and cell-cell contacts (i.e. forced single cell suspension assay - fSCS).

Findings: We proved that fSCS selects CRC cells with mesenchymal and pro-metastatic traits. Moreover, we found that the transposon insertions conferred CRC cells resistance to fSCS and thus metastatic advantage. Among the retrieved transposon insertions, we demonstrated that the one located in the 3'UTR of BTBD7 disrupts miR-23b::BTBD7 interaction and contributes to pro-metastatic traits. In addition, miR-23b and BTBD7 correlate with CRC metastasis both in preclinical experiments and in clinical samples.

Interpretation: fSCS is a simple and scalable in vitro assay to investigate pro-metastatic traits and transposon-based genetic screens can interrogate the non-coding part of the human genome (e.g. miRNA::target interactions). Finally, both Btbd7 and miR-23b represent promising prognostic biomarkers and therapeutic targets in CRC. FUND: This work was supported by Marie Curie Actions (CIG n. 303877) and Friuli Venezia Giulia region (Grant Agreement n°245574), Italian Association for Cancer Research (AIRC, MFAG n°13589), Italian Ministry of Health (GR-2010-2319387 and PE-2016-02361040) and 5x1000 to CRO Aviano.
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http://dx.doi.org/10.1016/j.ebiom.2019.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710852PMC
August 2019

Pathologist second opinion significantly alters clinical management of pT1 endoscopically resected colorectal cancer.

Virchows Arch 2019 Nov 17;475(5):665-668. Epub 2019 Jun 17.

Faculty of Medicine and Psychology, Department of Clinical and Molecular Medicine, University of Rome "Sapienza", Santo Andrea Hospital, via di Grottarossa 1035, 00189, Rome, Italy.

We retrospectively collected a series of 82 endoscopically removed early colorectal cancers. Histological specimens were revised by two gastrointestinal pathologists, performing a re-evaluation of all risk factors for lymph node metastasis. The comparison between second opinion and first pathological report revealed that lymphovascular invasion and tumor grading showed a lower level of concordance than other parameters. Our results demonstrated that second opinion modified risk assessment in about 10% of cases. It was mainly due to a lack in reporting of some parameters at the first diagnosis and a different evaluation in second opinion for updated guidelines. Considering the subgroup of patients with modified risk assessment, clinical data revealed that tumors, re-classified as low risk, did not develop lymph node metastasis that, conversely, occurred in patients identified as high risk by second opinion. In conclusion, second opinion significantly alters risk perception of endoscopically removed early colorectal carcinomas representing a valuable tool for their appropriate clinical management.
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http://dx.doi.org/10.1007/s00428-019-02603-yDOI Listing
November 2019

USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability.

Sci Adv 2019 05 8;5(5):eaav3235. Epub 2019 May 8.

Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy.

Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated with tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked to tumor spreading is not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance to platinum, by regulating the stability of Snail, which, in turn, promotes tumor dissemination. At the molecular level, we observed that upon platinum treatment, USP1 is phosphorylated by ATM and ATR and binds to Snail. Then, USP1 de-ubiquitinates and stabilizes Snail expression, conferring resistance to platinum, increased stem cell-like features, and metastatic ability. Consistently, knockout or pharmacological inhibition of USP1 increased platinum sensitivity and decreased metastatic dissemination in a Snail-dependent manner. Our findings identify Snail as a USP1 target and open the way to a novel strategy to overcome platinum resistance and more successfully treat patients with ovarian cancer.
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http://dx.doi.org/10.1126/sciadv.aav3235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506239PMC
May 2019

p27kip1 at the crossroad between actin and microtubule dynamics.

Cell Div 2019 1;14. Epub 2019 Apr 1.

1Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy.

The p27 protein, mainly known as a negative regulator of cell proliferation, has also been involved in the control of other cellular processes, including the regulation of cytoskeleton dynamics. Notably, these two functions involve distinct protein domains, residing in the N- and C-terminal halves, respectively. In the last two decades, p27 has been reported to interact with microtubule and acto-myosin cytoskeletons, both in direct and indirect ways, overall drawing a picture in which several factors play their role either in synergy or in contrast one with another. As a result, the role of p27 in cytoskeleton dynamics has been implicated in cell migration, both in physiologic and in neoplastic contexts, modulating cytokinesis, lipid raft trafficking, and neuronal development. Recently, two distinct papers have further reported a central role for p27 in the control of microtubule stability and post-translational modifications, dissecting the interaction between p27 and α-tubulin-acetyl-transferase (α-TAT), an enzyme involved in the stability of microtubules, and protein-regulator of cytokinesis 1 (PRC1), a nuclear regulator of the central spindle during mitosis. In light of these recent evidences, we will comment on the role of p27 on cytoskeleton regulation and its implication for cancer progression.
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http://dx.doi.org/10.1186/s13008-019-0045-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442415PMC
April 2019

Clinical management of endoscopically resected pT1 colorectal cancer.

Endosc Int Open 2018 Dec 12;6(12):E1462-E1469. Epub 2018 Dec 12.

Endoscopy Unit, Azienda Ospedaliera Sant'Andrea, "Sapienza" University of Rome, Rome, Italy.

 Implementation of colorectal cancer (CRC) screening programs increases endoscopic resection of polyps with early invasive CRC (pT1). Risk of lymph node metastasis often leads to additional surgery, but despite guidelines, correct management remains unclear. Our aim was to assess the factors affecting the decision-making process in endoscopically resected pT1-CRCs in an academic center.  We retrospectively reviewed patients undergoing endoscopic resection of pT1 CRC from 2006 to 2016. Clinical, endoscopic, surgical treatment, and follow-up data were collected and analyzed. Lesions were categorized according to endoscopic/histological risk-factors into low and high risk groups. Comorbidities were classified according to the Charlson comorbidity index (CCI). Surgical referral for each group was computed, and dissociation from current European CRC screening guidelines recorded. Multivariate analysis for factors affecting the post-endoscopic surgery referral was performed.  Seventy-two patients with endoscopically resected pT1-CRC were included. Overall, 20 (27.7 %) and 52 (72.3 %) were classified as low and high risk, respectively. In the low risk group, 11 (55 %) were referred to surgery, representing over-treatment compared with current guidelines. In the high risk group, nonsurgical endoscopic surveillance was performed in 20 (38.5 %) cases, representing potential under-treatment. After a median follow-up of 30 (6 - 130) months, no patients developed tumor recurrence. At multivariate analysis, age (OR 1.21, 95 %CI 1.02 - 1.42;  = 0.02) and CCI (OR 1.67, 95 %CI 1.12 - 3.14;  = 0.04) were independent predictors for subsequent surgery.  A substantial rate of inappropriate post-endoscopic treatment of pT1-CRC was observed when compared with current guidelines. This was apparently related to an overestimation of patient-related factors rather than endoscopically or histologically related factors.
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http://dx.doi.org/10.1055/a-0781-2293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291400PMC
December 2018

Stathmin Is Required for Normal Mouse Mammary Gland Development and Δ16HER2-Driven Tumorigenesis.

Cancer Res 2019 01 26;79(2):397-409. Epub 2018 Nov 26.

Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Aviano, Italy.

Postnatal development of the mammary gland relies on the maintenance of oriented cell division and apicobasal polarity, both of which are often deregulated in cancer. The microtubule (MT) network contributes to control these processes; however, very little is known about the impact of altered MT dynamics in the development of a complex organ and on the role played by MT-interacting proteins such as stathmin. In this study, we report that female stathmin knock-out (STM KO) mice are unable to nurse their litters due to frank impairment of mammary gland development. In mouse mammary epithelial cells, loss of stathmin compromised the trafficking of polarized proteins and the achievement of proper apicobasal polarity. In particular, prolactin receptor internalization and localization was altered in STM KO mammary epithelial cells, leading to decreased protein stability and downmodulation of the Prl/PrlR/STAT5 signaling pathway. Absence of stathmin induced alterations in mitotic spindle orientation, accumulation of mitotic defects, and apoptosis, overall contributing to tissue disorganization and further decreasing the expansion of the mammary epithelial compartment. Loss of stathmin in MMTV-Δ16HER2 transgenic mice decreased the incidence and increased the latency of these very aggressive mammary carcinomas. Collectively, these data identify the essential mammary protein stathmin as protumorigenic and suggest it may serve as a potential therapeutic target in breast cancer. SIGNIFICANCE: Stathmin expression is critical to maintain oriented cell division and apicobasal polarity in normal mammary glands and to establish a protumorigenic program that eventually sustains HER2-positive breast cancer formation in mice.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2488DOI Listing
January 2019

Exploring the Role of Fallopian Ciliated Cells in the Pathogenesis of High-Grade Serous Ovarian Cancer.

Int J Mol Sci 2018 Aug 24;19(9). Epub 2018 Aug 24.

Division of Molecular Oncology, Department of Translational Research, IRCCS CRO Aviano-National Cancer Institute, Via Franco Gallini, 2 33081 Aviano PN, Italy.

High-grade serous epithelial ovarian cancer (HGSOC) is the fifth leading cause of cancer death in women and the first among gynecological malignancies. Despite an initial response to standard chemotherapy, most HGSOC patients relapse. To improve treatment options, we must continue investigating tumor biology. Tumor characteristics (e.g., risk factors and epidemiology) are valuable clues to accomplish this task. The two most frequent risk factors for HGSOC are the lifetime number of ovulations, which is associated with increased oxidative stress in the pelvic area caused by ovulation fluid, and a positive family history due to genetic factors. In the attempt to identify novel genetic factors (i.e., genes) associated with HGSOC, we observed that several genes in linkage with HGSOC are expressed in the ciliated cells of the fallopian tube. This finding made us hypothesize that ciliated cells, despite not being the cell of origin for HGSOC, may take part in HGSOC tumor initiation. Specifically, malfunction of the ciliary beat impairs the laminar fluid flow above the fallopian tube epithelia, thus likely reducing the clearance of oxidative stress caused by follicular fluid. Herein, we review the up-to-date findings dealing with HGSOC predisposition with the hypothesis that fallopian ciliated cells take part in HGSOC onset. Finally, we review the up-to-date literature concerning genes that are located in genomic loci associated with epithelial ovarian cancer (EOC) predisposition that are expressed by the fallopian ciliated cells.
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http://dx.doi.org/10.3390/ijms19092512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163198PMC
August 2018

Optimized immunohistochemistry using the D5F3 antibody provides a reliable test for identification of ALK-positive lung adenocarcinomas.

Virchows Arch 2017 Jul 17;471(1):123-127. Epub 2017 May 17.

Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy.

We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative. The FISH positive/IHC-positive cases with moderately intense reactivity had the typical clinicopathologic features of ALK-positive patients (younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01; cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In conclusion, our findings indicate that optimized IHC using the D5F3 antibody provides a reliable and inexpensive test for identification of ALK-positive adenocarcinomas. Inclusion of this information in the pathology report at the time of the histological diagnosis might significantly shorten time to treatment.
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http://dx.doi.org/10.1007/s00428-017-2145-8DOI Listing
July 2017

Oncocytic Variant of Medullary Thyroid Carcinoma: A Rare Case of Sporadic Multifocal and Bilateral Wild-Type Neoplasm with Revision of the Literature.

Rare Tumors 2016 Nov 20;8(4):6537. Epub 2016 Dec 20.

Department of Pathology, Sant'Andrea Hospital, University Sapienza of Rome , Gemelli Hospital, Rome Italy.

Oncocytic variant of medullary thyroid carcinoma (OV-MTC) is a very unusual entity, up to date only 17 cases have been reported in the literature. MTC is a neuro-endocrine malignancy arising from the para-follicular C cells of the thyroid gland. It generally has a slight female predominance and appears as a single lesion. However in the Multiple Endocrine Neoplasia Syndrome 2, linked to the point mutation of oncogene, multifocal MTCs may also occur. Herein, we report the case of a 75 years old man with a rare form of sporadic multifocal and bilateral OV-MTC expressing wild-type gene. The histological and molecular features of this rare entity are presented and discussed with revision of the pertinent literature.
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http://dx.doi.org/10.4081/rt.2016.6537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226050PMC
November 2016

Diffuse Follicular Variant of Papillary Thyroid Carcinoma: A Case Report with a Revision of Literature.

Rare Tumors 2016 Nov 20;8(4):6536. Epub 2016 Dec 20.

Department of Pathology, Sant'Andrea Hospital, University Sapienza of Rome , Italy.

The diffuse follicular variant of papillary thyroid carcinoma (DFV-PTC) is a rare malignant thyroid condition. It represents an uncommon variant of papillary carcinoma characterized by a diffuse involvement of thyroid parenchyma, follicular architecture and nuclear features of PTC in absence of a surrounding capsule. Up to date few data have been collected about this entity and, at the best of our knowledge, only 24 cases have been reported in the literature. According to these reports DFV-PTC seems to occur preferentially in young women and shows more aggressive behavior than other papillary thyroid tumors. Herein we present an unusual case of DFV-PTC occurring in an 83 years old woman, involving the entire thyroid gland, without distinct or prevalent thyroid nodules. The tumor was clinically misdiagnosed as obstructive goiter.
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http://dx.doi.org/10.4081/rt.2016.6536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226049PMC
November 2016

Hyperandrogenism in a postmenopausal woman: a rare case of ectopic adrenal cortical gland.

Gynecol Endocrinol 2017 Mar 19;33(3):185-187. Epub 2017 Jan 19.

a Department of Medical and Surgical Sciences and Translational Medicine and.

Most frequent causes of androgenic manifestation are Cushing's syndrome, PCO, benign and malignant androgen-secreting non adrenal tumors and iatrogenic hirsutism. Hyperplasia or neoplasms of ectopic adrenocortical gland are rare. We report a case of a 63-year old female with hirsutism and alopecia. Laboratory data highlighted increased levels of androgens. Diagnostic imaging revealed normal morphology of adrenocortical gland and ovaries. In view of the clinical picture and suspected diagnosis of extra-adrenal cause, she underwent bilateral salpingo-oophorectomy. Histologic examination showed an ectopic adrenal gland with adenoma in the ovarian and peri-ovarian tissue. At six months of follow up, the patients has no sign of hyperandrogenism. In case of hyperandrogenism in postmenopausal women and in the absence of the adrenocortical gland abnormality, ovarian origin should be considered in the differential diagnosis.
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http://dx.doi.org/10.1080/09513590.2016.1252326DOI Listing
March 2017

Influence of perineural invasion in predicting overall survival and disease-free survival in patients With locally advanced gastric cancer.

Am J Surg 2017 Apr 29;213(4):748-753. Epub 2016 Jul 29.

Department of General Surgery, University of Rome, "La Sapienza", Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy.

Background: The aim of the present study was to evaluate the prognostic significance of perineural invasion (PNI) in locally advanced gastric cancer patients who underwent D2 gastrectomy and adjuvant chemotherapy.

Methods: The records of a series of 103 patients undergoing D2 gastrectomy with curative intent combined with adjuvant chemotherapy from January 2004 to December 2014 were retrospectively reviewed.

Results: PNI was positive in 47 (45.6%) specimens. The 1-, 3-, and 5-year overall survival rates were 81%, 55%, and 42%, respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 76%, 57%, and 49%, respectively. A multivariate analysis showed that age number of positive lymph nodes, T stage, and PNI were independently associated with overall survival. Regarding DFS, the multivariate analysis showed that only PNI was independently associated with DFS.

Conclusions: PNI and T stage and positive lymph nodes are independent markers of poor prognosis in patients with gastric cancer. PNI should be incorporated in the postoperative staging system for planning follow-up after surgery and in our opinion to propose more aggressive postoperative therapies in PNI-positive patients.
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http://dx.doi.org/10.1016/j.amjsurg.2016.05.022DOI Listing
April 2017

High prevalence of ALK+/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults.

Lung Cancer 2016 07 2;97:95-8. Epub 2016 May 2.

Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University, Rome, Italy. Electronic address:

Objectives: To investigate prevalence and age-distribution of ALK- or ROS1-translocated adenocarcinomas in patients ≤50 years of age.

Materials And Methods: Paraffin sections of pulmonary adenocarcinoma were analyzed for ALK (637 cases) and ROS1 (376 cases) translocations using FISH, and for EGFR mutations (789 cases) using mutant-specific Real-Time PCR.

Results: ALK or ROS1 fusions were detected in 55 of 637 cases (8.6%). When patients were stratified for age, it was found that six of six cases (100%) of lung adenocarcinoma diagnosed in patients <30 years of age were translocated for ALK (4 cases) or ROS1 (2 cases). With the increase of age, there was a gradual decrease in the percentage of positive cases. In fact, ALK-translocated or ROS1-translocated cases were 5 of 17 cases (29%) in the 31-40 years age-group, 6 of 46 cases (13%) in the 41-50 years age-group, and 38 of 568 cases (7.0%) in patients older than 50 years. The six patients <30 years of age (5F/1M), including two pediatric patients (≤18 years old), presented with stage IV disease, were never or light smoker, and had no family history of pulmonary tumours. Four of the six patients, were treated with crizotinib and had an objective response.

Conclusions: Our findings provide evidence that ALK or ROS1 translocations are crucial events in tumourigenesis of pulmonary adenocarcinoma of very young patients, including pediatric patients.
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http://dx.doi.org/10.1016/j.lungcan.2016.04.022DOI Listing
July 2016

Transitional cell carcinoma of the retrorectal space arisen in tailgut cyst: a case report and review of the literature.

Int J Surg Pathol 2014 May 1;22(3):280-5. Epub 2013 Jul 1.

1University "Sapienza," Rome, Italy.

Tailgut cysts, also known as retrorectal cystic hamartomas, are congenital lesions derived by an abnormal remnant of the postanal primitive hindgut, consisting of unilocular or multilocular cysts usually lined by squamous, transitional, or glandular epithelium. Malignant transformation is an uncommon event, and it mainly involves the neuroendocrine or glandular epithelium; other histotypes are sporadic. Here, we report, for the first time, the clinicopathological features of a transitional cell carcinoma that arose in a tailgut cyst.
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http://dx.doi.org/10.1177/1066896913491324DOI Listing
May 2014