Publications by authors named "Francesco Fortarezza"

26 Publications

  • Page 1 of 1

P14/ARF-Positive Malignant Pleural Mesothelioma: A Phenotype With Distinct Immune Microenvironment.

Front Oncol 2021 22;11:653497. Epub 2021 Mar 22.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Introduction: The CDKN2A gene plays a central role in the pathogenesis of malignant pleural mesothelioma (MPM). The gene encodes for two tumor suppressor proteins, p16/INK4A and p14/ARF, frequently lost in MPM tumors. The exact role of p14/ARF in MPM and overall its correlation with the immune microenvironment is unknown. We aimed to determine whether there is a relationship between p14/ARF expression, tumor morphological features, and the inflammatory tumor microenvironment.

Methods: Diagnostic biopsies from 76 chemo-naive MPMs were evaluated. Pathological assessments of histotype, necrosis, inflammation, grading, and mitosis were performed. We evaluated p14/ARF, PD-L1 (tumor proportion score, TPS), and Ki-67 (percentage) by immunohistochemistry. Inflammatory cell components (CD3+, CD4+, CD8+ T lymphocytes; CD20+ B-lymphocytes; CD68+ and CD163+ macrophages) were quantified as percentages of positive cells, distinguishing between intratumoral and peritumoral areas. The expression of p14/ARF was associated with several clinical and pathological characteristics. A random forest-based machine-learning algorithm (Boruta) was implemented to identify which variables were associated with p14/ARF expression.

Results: p14/ARF was evaluated in 68 patients who had a sufficient number of tumor cells. Strong positivity was detected in 14 patients (21%) (11 epithelioid and 3 biphasic MPMs). At univariate analysis, p14/ARF-positive epithelioid mesotheliomas showed higher nuclear grade (G3) (p = 0.023) and higher PD-L1 expression (≥50%) (p = 0.042). The percentages of CD4 and CD163 in peritumoral areas were respectively higher and lower in p14/ARF positive tumors but did not reach statistical significance with our sample size (both p = 0.066). The Boruta algorithm confirmed the predictive value of PD-L1 percentage for p14/ARF expression in all histotypes.

Conclusions: p14/ARF-positive epithelioid mesotheliomas may mark a more aggressive pathological phenotype (higher nuclear grade and PD-L1 expression). Considering the results regarding the tumor immune microenvironment, p14/ARF-negative tumors seem to have an immune microenvironment less sensitive to immune checkpoint inhibitors, being associated with low PD-L1 and CD4 expression, and high CD163 percentage. The association between p14/ARF-positive MPMs and PD-L1 expression suggests a possible interaction of the two pathways. Confirmation of our preliminary results could be important for patient selection and recruitment in future clinical trials with anticancer immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.653497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019896PMC
March 2021

Machine learning-based analysis of alveolar and vascular injury in SARS-CoV-2 acute respiratory failure.

J Pathol 2021 Feb 24. Epub 2021 Feb 24.

Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padua Medical School, Padua, Italy.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumopathy is characterized by a complex clinical picture and heterogeneous pathological lesions, both involving alveolar and vascular components. The severity and distribution of morphological lesions associated with SARS-CoV-2 and how they relate to clinical, laboratory, and radiological data have not yet been studied systematically. The main goals of the present study were to objectively identify pathological phenotypes and factors that, in addition to SARS-CoV-2, may influence their occurrence. Lungs from 26 patients who died from SARS-CoV-2 acute respiratory failure were comprehensively analysed. Robust machine learning techniques were implemented to obtain a global pathological score to distinguish phenotypes with prevalent vascular or alveolar injury. The score was then analysed to assess its possible correlation with clinical, laboratory, radiological, and tissue viral data. Furthermore, an exploratory random forest algorithm was developed to identify the most discriminative clinical characteristics at hospital admission that might predict pathological phenotypes of SARS-CoV-2. Vascular injury phenotype was observed in most cases being consistently present as pure form or in combination with alveolar injury. Phenotypes with more severe alveolar injury showed significantly more frequent tracheal intubation; longer invasive mechanical ventilation, illness duration, intensive care unit or hospital ward stay; and lower tissue viral quantity (p < 0.001). Furthermore, in this phenotype, superimposed infections, tumours, and aspiration pneumonia were also more frequent (p < 0.001). Random forest algorithm identified some clinical features at admission (body mass index, white blood cells, D-dimer, lymphocyte and platelet counts, fever, respiratory rate, and PaCO ) to stratify patients into different clinical clusters and potential pathological phenotypes (a web-app for score assessment has also been developed; https://r-ubesp.dctv.unipd.it/shiny/AVI-Score/). In SARS-CoV-2 positive patients, alveolar injury is often associated with other factors in addition to viral infection. Identifying phenotypical patterns at admission may enable a better stratification of patients, ultimately favouring the most appropriate management. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014445PMC
February 2021

The Immunopathological and Histological Landscape of COVID-19-Mediated Lung Injury.

Int J Mol Sci 2021 01 19;22(2). Epub 2021 Jan 19.

Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, 35121 Padua, Italy.

A complete understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) physiopathology and related histopathologic lesions is necessary to improve treatment and outcome of coronavirus disease 2019 (COVID-19) patients. Many studies have focused on autopsy findings in COVID-19-related deaths to try and define any possible specific pattern. Histopathologic alterations are principally found within lungs and blood vessels, and these abnormalities also seem to have the highest clinical impact. Nevertheless, many of the morphological data collected so far are non-specific, fickle, and possibly associated with other co-existing factors. The aim of this minireview is to describe the main histopathological features related to COVID-19 and the mechanism known as "cytokine storm".
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http://dx.doi.org/10.3390/ijms22020974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835817PMC
January 2021

[Histopathological features due to the SARS-CoV-2].

Ann Pathol 2021 Feb 30;41(1):9-22. Epub 2020 Dec 30.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Medical School, Padova, Italie.

The infection due to the SARS-CoV-2 leads lesions mainly observed at the respiratory tract level, but not exclusively. The analyses of these lesions benefited from different autopsy studies. Thus, these lesions were observed in different organs, tissues and cells. These observations allowed us to rapidly improve the knowledge of the pathophysiological mechanisms associated with this emergent infectious disease. The virus can be detected in formalin fixed paraffin embedded tissues using immunohistochemistry, in situ hybridization, molecular biology and/or electron microscopy approaches. However, many uncertainties are still present concerning the direct role of the SARS-CoV-2 on the different lesions observed in different organs, outside the lung, such as the heart, the brain, the liver, the gastrointestinal tract, the kidney and the skin. In this context, it is pivotal to keep going to increase the different tissue and cellular studies in the COVID-19 positive patients aiming to better understanding the consequences of this new infectious disease, notably considering different epidemiological and co-morbidities associated factors. This could participate to the development of new therapeutic strategies too. The purpose of this review is to describe the main histological and cellular lesions associated with the infection due to the SARS-CoV-2.
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http://dx.doi.org/10.1016/j.annpat.2020.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773006PMC
February 2021

Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH.

Diagnostics (Basel) 2020 Oct 15;10(10). Epub 2020 Oct 15.

Department of Emergency and Organ Transplantation (DETO), Pathology Section, Breast Unit Care, University of Bari, Medical School, 70124 Bari, Italy.

The breast phyllodes tumor is a biphasic tumor that accounts for less than of 1% of all breast neoplasms. It is classified as benign, borderline, or malignant, and can mimic benign masses. Some recurrent alterations have been identified. However, a precise molecular classification of these tumors has not yet been established. Herein, we describe a case of a 43-year-old woman that was admitted to the emergency room for a significant bleeding from the breast skin. A voluminous ulcerative mass of the left breast and multiple nodules with micro-calcifications on the right side were detected at a physical examination. A left total mastectomy and a nodulectomy of the right breast was performed. The histological diagnosis of the surgical specimens reported a bilateral giant phyllodes tumor, showing malignant features on the left and borderline characteristics associated with a fibroadenoma on the right. A further molecular analysis was carried out by an array-Comparative Genomic Hybridization (CGH) to characterize copy-number alterations. Many losses were detected in the malignant mass, involving several tumor suppressor genes. These findings could explain the malignant growth and the metastatic risk. In our study, genomic profiling by an array-CGH revealed a greater chromosomal instability in the borderline mass (40 total defects) than in the malignant (19 total defects) giant phyllodes tumor, reflecting the tumor heterogeneity. Should our results be confirmed with more sensitive and specific molecular tests (DNA sequencing and FISH analysis), they could allow a better selection of patients with adverse pathological features, thus optimizing and improving patient's management.
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http://dx.doi.org/10.3390/diagnostics10100825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602371PMC
October 2020

Combined Immunoscore for Prognostic Stratification of Early Stage Non-Small-Cell Lung Cancer.

Front Oncol 2020 25;10:564915. Epub 2020 Sep 25.

Oncology Unit 2, Istituto Oncologico Veneto IRCCS, Padua, Italy.

Background: To date, no combined immunoscore has been evaluated for prognostic stratification of early stage non-small-cell lung cancer (NSCLC). The main goal of this study was to investigate the prognostic impact of programmed death ligand 1 (PD-L1) expression and different immune cell components (CD4+, CD8+ T-lymphocytes, and CD68+ macrophages) in early stage NSCLC patients, distinguishing peritumoral (PT) and intratumoral (IT) localizations. The secondary aim was to identify a combined immunoscore to optimize the prognostic stratification of NSCLC patients.

Methods: This retrospective study included surgical specimens from consecutive chemo-naive stage II-III radically resected NSCLC patients. Immunohistochemistry was carried out to evaluate PD-L1 expression and to quantify IT and PT CD4+, CD8+ T-lymphocytes, and CD68+ macrophages. The impact of a single marker and of a combination of multiple markers on overall survival (OS) was investigated.

Results: Seventy-nine patients were included in the study. PD-L1 expression was associated with worse prognosis (3 years OS: 58% in high- compared with 67% in low-expressing tumors), even though without statistical significance. When integrating PT CD8+, CD4+, and CD68 into a combined PT immunoscore, a significant prognostic stratification of patients was obtained and confirmed at multivariate analysis (3 years OS: 86% in patients with low PT immunoscore vs. 59% in patients with high PT immunoscore, = 0.018). The integration of derived neutrophil/lymphocyte ratio (dNLR) with combined PT immunoscore improved prognostic stratification, with longer OS in patients with low PT immunoscore and low dNLR ( = 0.002).

Conclusion: The combined PT immunoscore (CD8+, CD4+, and CD68) integrated with dNLR may be a promising marker for the development of an integrated Tumor, Node, Metastasis (TNM) immunoscore.
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http://dx.doi.org/10.3389/fonc.2020.564915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544833PMC
September 2020

COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City.

Mod Pathol 2020 11 2;33(11):2156-2168. Epub 2020 Sep 2.

Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

SARS-CoV-2, the etiologic agent of COVID-19, is a global pandemic with substantial mortality dominated by acute respiratory distress syndrome. We systematically evaluated lungs of 68 autopsies from 3 institutions in heavily hit areas (2 USA, 1 Italy). Detailed evaluation of several compartments (airways, alveolar walls, airspaces, and vasculature) was performed to determine the range of histologic features. The cohort consisted of 47 males and 21 females with a median age of 73 years (range 30-96). Co-morbidities were present in most patients with 60% reporting at least three conditions. Tracheobronchitis was frequently present, independent from intubation or superimposed pneumonia. Diffuse alveolar damage (DAD) was seen in 87% of cases. Later phases of DAD were less frequent and correlated with longer duration of disease. Large vessel thrombi were seen in 42% of cases but platelet (CD61 positive) and/or fibrin microthrombi were present at least focally in 84%. Ultrastructurally, small vessels showed basal membrane reduplication and significant endothelial swelling with cytoplasmic vacuolization. In a subset of cases, virus was detected using different tools (immunohistochemistry for SARS-CoV-2 viral spike protein, RNA in situ hybridization, lung viral culture, and electron microscopy). Virus was seen in airway epithelium and type 2 pneumocytes. IHC or in situ detection, as well as viable form (lung culture positive) was associated with the presence of hyaline membranes, usually within 2 weeks but up to 4 weeks after initial diagnosis. COVID-19 pneumonia is a heterogeneous disease (tracheobronchitis, DAD, and vascular injury), but with consistent features in three centers. The pulmonary vasculature, with capillary microthrombi and inflammation, as well as macrothrombi, is commonly involved. Viral infection in areas of ongoing active injury contributes to persistent and temporally heterogeneous lung damage.
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http://dx.doi.org/10.1038/s41379-020-00661-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463226PMC
November 2020

Two Sorts of Microthrombi in a Patient With Coronavirus Disease 2019 and Lung Cancer.

J Thorac Oncol 2020 11 29;15(11):1782-1785. Epub 2020 Aug 29.

Anaesthesia and Intensive Care Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.

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http://dx.doi.org/10.1016/j.jtho.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455572PMC
November 2020

A Single Liver Metastasis from Pleural Biphasic Mesothelioma.

Diagnostics (Basel) 2020 Aug 4;10(8). Epub 2020 Aug 4.

Department of Interdisciplinary Medicine, Occupational Health Division, University of Bari, 70124 Bari, Italy.

Virtually any malignancy can metastasize to the liver. Large solitary metastases are rare and can be difficult to distinguish from primary tumors. Malignant mesothelioma is often considered as a locally invasive cancer but tumor dissemination to extra-thoracic sites is possible, and the liver can be involved. Herein, we present a rare case of pleural mesothelioma with a solitary large liver metastasis diagnosed postmortem in a ninety-two-year-old man with 35 years of exposure to asbestos. Results of immunohistochemical staining of the pleural and liver tumor were similar, both positive for low-molecular weight keratins, calretinin, vimentin, and podoplanin, and negative for Claudin-4, TTF1, CEA, BerEP4, CK7, CK19, CK20, BAP1, Hep Par1, p40, and WT1. Fluorescent in-situ hybridization (FISH) for p16/CDKN2A was also performed and a homozygous deletion was detected in both tumors, supporting the diagnosis of mesothelioma. Reporting this case, we would like to point out that extra-thoracic dissemination from pleural mesothelioma, even if exceptional, can occur. In cases where differential diagnoses are challenging, the value of ancillary techniques and a practical approach to diagnostic work-up is of primary importance.
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http://dx.doi.org/10.3390/diagnostics10080555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460021PMC
August 2020

Polyomavirus nephritis-associated urothelial hyperplasia in a kidney allograft.

Kidney Int 2020 08;98(2):518

Department of Emergency and Organ Transplant - Pathology Division, University of Bari, Bari, Italy.

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http://dx.doi.org/10.1016/j.kint.2020.02.016DOI Listing
August 2020

Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists.

Virchows Arch 2020 Sep 9;477(3):359-372. Epub 2020 Jul 9.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Medical School, Via A. Gabelli 61, 35121, Padova, Italy.

Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.
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http://dx.doi.org/10.1007/s00428-020-02886-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343579PMC
September 2020

Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study.

Diagnostics (Basel) 2020 Jun 9;10(6). Epub 2020 Jun 9.

Occupational Health Division, Department of Interdisciplinary Medicine, University of Bari, 70124 Bari, Italy.

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with a poor survival. Although some advances in knowledge have been obtained for the pleural form, much less is known about DMPM. Advantages in terms of prognosis are still limited and strong efforts need to be made. The aim of our study was to correlate several histological and molecular factors with survival in a large cohort of 45 DMPMs. We evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, desmoplastic reaction, Ki67 percentage, WT-1 expression, p16 protein by immunohistochemistry and CDKN2A deletion by FISH. Our results showed that epithelioid histotype, nuclear grade 2, mitotic count ≤5 x mm, absence of desmoplasia and p16/CDKN2A deletion, low Ki67 value, and high WT-1 expression were correlated with the most prolonged survival ( = 0.0001). Moreover, p16 loss in immunohistochemistry reflected CDKN2A deletion detected with FISH, and both were correlated with the worst survival ( = 0.0001). At multivariate analysis, Ki67 value, WT-1 expression and p16/CDKN2A deletion emerged as independent prognostic factors ( = 0.01, = 0.0001 and = 0.01, respectively). These parameters are easy to analyse at the time of DMPM diagnosis and may support better patient stratification, prediction of treatment effectiveness and therapeutic optimization.
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http://dx.doi.org/10.3390/diagnostics10060386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345555PMC
June 2020

Immunohistochemical neuroendocrine marker expression in primary pulmonary NUT carcinoma: a diagnostic pitfall.

Histopathology 2020 09 28;77(3):508-510. Epub 2020 Jul 28.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Medical School, Padova, Italy.

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http://dx.doi.org/10.1111/his.14166DOI Listing
September 2020

Repair of Adult Benign Tracheoesophageal Fistulae With Absorbable Patches: Single-Center Experience.

Ann Thorac Surg 2020 04 22;109(4):1086-1094. Epub 2019 Nov 22.

Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy. Electronic address:

Background: This group previously reported on the repair of a wide tracheoesophageal fistula with a bioabsorbable patch. The current study describes a consecutive series of patients operated on using the same technique.

Methods: Data of patients undergoing surgical closure of tracheoesophageal fistula at a single center from 2011 to 2018 were extracted and analyzed.

Results: An absorbable patch was used in 8 of 23 patients (34.8%) operated on for tracheoesophageal fistula during the study period. Causes of the fistulae included postintubation injury (n = 6), mediastinal radiotherapy (n = 1), and a complication of lung resection (n = 1). The median fistula size was 27.5 mm (range, 15 to 45 mm). In 3 patients, the surgical approach was through cervicotomy and in 5 it was through right thoracotomy. Prosthetic materials consisted of Gore Bio-A (W.L. Gore & Associates, Inc, Newark, DE) tissue reinforcement in 6 patients and polyglactin 910 knitted mesh in 2 patients. In every case, the prosthesis was covered with a pedicled muscle flap. The esophageal defect was treated by primary closure in 7 patients and by esophageal exclusion in 1. Fistula recurrence and postoperative death occurred in 1 patient (12.5%), whereas 7 patients experienced postoperative complications (87.5%). Five patients resumed oral intake, and 3 breathed without a tracheal appliance. Compared with the other patients, in those who underwent repair of their fistula using a prosthesis, the median size of the airway defect was larger, morbidity was greater, and the rate of resumption of oral intake was lower.

Conclusions: Repair of tracheoesophageal fistulae with synthetic prostheses is feasible and may be effective in complex cases. Further research is needed to identify the ideal prosthetic material.
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http://dx.doi.org/10.1016/j.athoracsur.2019.09.081DOI Listing
April 2020

Unexpected pleural finding after a fall.

Lancet Oncol 2019 10 30;20(10):e606. Epub 2019 Sep 30.

Pathological Anatomy and Thoracic Surgery, Department of Cardiac, Thoracic, Vascular Sciences and Public Health - DCTV, University of Padova Medical School, Padova, Italy. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(19)30505-4DOI Listing
October 2019

Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling.

Cancers (Basel) 2019 Sep 12;11(9). Epub 2019 Sep 12.

Department of Biomedical Sciences and Medical Oncology, University of Bari "Aldo Moro", 70124 Bari, Italy.

Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidence suggests that the deregulation of mitochondrial biogenesis, morphology, dynamics, and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and 16 OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mitochondrial DNA (mtDNA) content was measured by real-time-PCR, protein levels were determined by Western blotting, and mitochondrial number and structure were measured by electron microscopy. Statistical analysis was performed using Student's -test, Mann-Whitney U test, and principal component analysis (PCA). We found, in OC, that increased mitochondrial number associated with increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial transcription factor A (TFAM) protein levels, as well as mtDNA content. The OC mitochondria presented an increased maximum length, as well as reduced cristae width and junction diameter, associated with increased optic atrophy 1 protein (OPA1) and prohibitin 2 (PHB2) protein levels. In addition, in OC tissues, augmented cAMP and sirtuin 3 (SIRT3) protein levels were observed. PCA of the 25 analyzed biochemical parameters classified OC patients in a distinct group from controls. We highlight a "mitochondrial signature" in OC that could result from cooperation of the cAMP pathway with the SIRT3, OPA1, and PHB2 proteins.
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http://dx.doi.org/10.3390/cancers11091350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770021PMC
September 2019

Airway Histopathology of Adolescent Survivors of Bronchopulmonary Dysplasia.

J Pediatr 2019 08 7;211:215-218. Epub 2019 May 7.

Department of Woman's and Child's Health - University Hospital of Padova, Padova, Italy. Electronic address:

Long-term survivors of bronchopulmonary dysplasia develop chronic obstructive lung disease. Herein we report in vivo histopathology from bronchial biopsies of 3 adolescent survivors of severe bronchopulmonary dysplasia. Thickened basement membranes with lymphocytic infiltrates and signs of immature neoangiogenesis in the absence of T-helper lymphocytes or eosinophils suggest the presence of an ongoing active airway process.
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http://dx.doi.org/10.1016/j.jpeds.2019.04.006DOI Listing
August 2019

Thymic Carcinoma With Thyroid Transcription Factor-1 Expression: An Insidious Pitfall.

J Thorac Oncol 2019 Apr;14(4):e68-e70

Thoracic Surgery Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2018.09.030DOI Listing
April 2019

Are There New Biomarkers in Tissue and Liquid Biopsies for the Early Detection of Non-Small Cell Lung Cancer?

J Clin Med 2019 Mar 26;8(3). Epub 2019 Mar 26.

University Côte d'Azur, CNRS, INSERM, IRCAN, Team 4, FHU OncoAge, 06001 Nice, France.

Lung cancer is one of the most lethal malignancies worldwide, mainly due to its late diagnoses. The detection of molecular markers on samples provided from routine bronchoscopy including several liquid-based cytology tests (e.g., bronchoaspirate, bronchoalveolar lavage) and/or on easily obtained specimens such as sputum could represent a new approach to improve the sensitivity in lung cancer diagnoses. Recently growing interest has been reported for "noninvasive" liquid biopsy as a valuable source for molecular profiling. Unfortunately, a biomarker and/or composition of biomarkers capable of detecting early-stage lung cancer has yet to be discovered even if in the last few years there has been, through the use of revolutionary new technologies, an explosion of lung cancer biomarkers. Assay sensitivity and specificity need to be improved particularly when new approaches and/or tools are used. We have focused on the most important markers detected in tissue, and on several cytological specimens and liquid biopsies overall.
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http://dx.doi.org/10.3390/jcm8030414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463117PMC
March 2019

Are there any theranostic biomarkers in small cell lung carcinoma?

J Thorac Dis 2019 Jan;11(Suppl 1):S102-S112

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova Medical School, Padova, Italy.

Small cell lung cancer (SCLC), an aggressive lung tumour with a poor prognosis, has a high load of somatic mutations, mainly induced by tobacco carcinogens given the strong association with smoking. Advances in genomic, epigenetic and proteomic profiling have significantly improved our understanding of the molecular and cellular biology of SCLC. Given the high mutational burden of SCLC the immune microenvironment is another exciting area under investigation even if it seems to be quite distinct from that of other solid tumours. In this review we will outline the current progress in molecular etiology of SCLC mentioning some key markers considered promising theranostic biomarkers.
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http://dx.doi.org/10.21037/jtd.2018.12.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353747PMC
January 2019

Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma.

Lung Cancer 2018 12 27;126:106-111. Epub 2018 Oct 27.

Department of Emergency and Organ Transplantation, Pathology Division, University of Bari, Italy. Electronic address:

Introduction: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.

Materials And Methods: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.

Results: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.

Discussion: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.
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http://dx.doi.org/10.1016/j.lungcan.2018.10.012DOI Listing
December 2018

Primary melanoma of the testis: myth.

Ann Transl Med 2018 Apr;6(7):135

Division of Pathology, Department of Emergency and Organ Transplantation (DETO), Aldo Moro University, Medical School, Bari, Italy.

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http://dx.doi.org/10.21037/atm.2018.02.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015938PMC
April 2018

T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity.

Gastroenterol Res Pract 2017 7;2017:5023680. Epub 2017 Dec 7.

Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro", Bari, Italy.

Background And Aims: Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation.

Materials And Methods: We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni's tests were used for statistical analysis.

Results: Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes; < 0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm; < 0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes, < 0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm; = 0.009).

Conclusions: The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS.
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http://dx.doi.org/10.1155/2017/5023680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738582PMC
December 2017

An intravascular papillary endothelial hyperplasia of the hand radiologically mimicking a hemangiopericytoma: A case report and literature review.

SAGE Open Med Case Rep 2018 10;6:2050313X17752851. Epub 2018 Jan 10.

Orthopaedic, Trauma and Spine Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, School of Medicine, University of Bari Aldo Moro and AOU Consorziale Policlinico, Bari, Italy.

Intravascular papillary endothelial hyperplasia is a rare benign vascular lesion of the skin and subcutaneous tissues, characterized by a reactive proliferation of endothelial cells that can present de novo in normal blood vessels (primary intravascular papillary endothelial hyperplasia), but it can also develop from a pre-existing vascular process (type II intravascular papillary endothelial hyperplasia), or it can arise in an extravascular location from a post-traumatic haematoma. The differential diagnosis between intravascular papillary endothelial hyperplasia and malignant vascular tumours can be challenging, due to the lacking of a specific radiologic description. We present a case of intravascular papillary endothelial hyperplasia of the hand radiologically mimicking a hemangiopericytoma.
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http://dx.doi.org/10.1177/2050313X17752851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768252PMC
January 2018

A 75-year-old woman presenting with nasal vestibulitis.

Infection 2018 08 2;46(4):579-580. Epub 2017 Nov 2.

Section of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari, Bari, Italy.

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http://dx.doi.org/10.1007/s15010-017-1087-zDOI Listing
August 2018

Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array.

Int J Mol Sci 2017 Aug 22;18(8). Epub 2017 Aug 22.

Department of Interdisciplinary Medicine, Occupational Health Division, Medical School, University of Bari, 70124 Bari, Italy.

Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods And Results: Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1→q13, 8p23.1, 9p12→p11, 9q21.33→q33.1, 9q12→q21.33, and 17p12→p11.2 are observed. Chromosome band 3p21 (), 9p21 () and 22q12 () are not affected. the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM).
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http://dx.doi.org/10.3390/ijms18081818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578204PMC
August 2017