Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab.

To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression.

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22).

Background: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.

Methods: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed.

Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients.

This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers' expression, their association with other variables and prognostic value.

TLR4 Expression in Ex-Lichenoid Lesions-Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment.

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment.

Mutations in the telomerase reverse transcriptase promoter and PIK3CA gene are common events in penile squamous cell carcinoma of Italian and Ugandan patients.

Penile carcinoma develops either through human papillomavirus (HPV) related or unrelated carcinogenic pathways. Genetic alterations and nucleotide changes in coding regions (ie, TP53, CDKN2A, PIK3CA and NOTCH1) are main cancer driver events either in HPV positive or in HPV negative tumours. We investigated the presence of hotspot nucleotide mutations in TERT promoter (TERTp) and PIK3CA exon 9 and their relationship with HPV status in 69 penile cancer cases from Italian and Ugandan patients.

Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database.

Objective: Only 10-15% of serous borderline ovarian tumors (BOTs) with extra-ovarian disease have invasive implants, and conservative treatments have been rarely reported. The MITO14 is a multi-institutional retrospective study conducted with the aim of systematically collecting data from consecutive BOT patients. The present analysis reports the oncological and reproductive outcomes of women with serous BOT and invasive implants registered into the MITO14 database and conservatively treated between August 2002 and May 2019.

AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization.

High-grade serous ovarian cancer (HGSOC) is among the deadliest gynecological malignancies. The acquired resistance to platinum-based therapies and the intrinsic heterogeneity of the disease contribute to the low survival rate. To improve patients' outcomes, new combinatorial approaches able to target different tumor vulnerabilities and enhance the efficacy of the current therapies are required.

Evaluation of Angiogenesis-Related Genes as Prognostic Biomarkers of Bevacizumab Treated Ovarian Cancer Patients: Results from the Phase IV MITO16A/ManGO OV-2 Translational Study.

Background: Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment.

Malignant Sinonasal Tumors: Update on Histological and Clinical Management.

Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes.

Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database.

Objectives: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs).

Methods: A multi-institutional retrospective study was conducted within the MITO Group.

Results: A total of 91 patients were recruited.

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy.

Background: Chemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described.

Objective: To examine the incidence, duration, and reversibility of arthralgia.

Ovarian Cancer Translational Activity of the Multicenter Italian Trial in Ovarian Cancer (MITO) Group: Lessons Learned in 10 Years of Experience.

Ovarian cancer is the most lethal gynecological cancer, and despite years of research, with the exception of a BRCA mutation driving the use of PARP inhibitors, no new prognostic/predictive biomarkers are clinically available. Improvement in biomarker selection and validation may derive from the systematic inclusion of translational analyses into the design of clinical trials. In the era of personalized medicine, the prospective centralized collection of high-quality biological material, expert pathological revision, and association to well-controlled clinical data are important or even essential added values to clinical trials.

Immunohistochemical Analysis Revealed a Correlation between Musashi-2 and Cyclin-D1 Expression in Patients with Oral Squamous Cells Carcinoma.

Aim: Musashi 2 (MSI2), which is an RNA-binding protein, plays a fundamental role in the oncogenesis of several cancers. The aim of this study is to investigate the expression of MSI2 in Oral Squamous Cell Carcinoma (OSCC) and evaluate its correlation to clinic-pathological variables and prognosis.

Materials And Methods: A bioinformatic analysis was performed on data downloaded from The Cancer Genome Atlas (TCGA) database.

Targeting the Formyl Peptide Receptor type 1 to prevent the adhesion of ovarian cancer cells onto mesothelium and subsequent invasion.

Background: The biological behavior of epithelial ovarian cancer (EOC) is unique since EOC cells metastasize early to the peritoneum. Thereby, new anti-target agents designed to block trans-coelomic dissemination of EOC cells may be useful as anti-metastatic drugs. The Urokinase Plasminogen Activator Receptor (uPAR) is overexpressed in EOC tissues, and its truncated forms released in sera and/or ascitic fluid are associated with poor prognosis and unfavorable clinical outcome.

Application of the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) to patients conservatively treated: Outcomes from an institutional series.

Objective: To test the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and determine the frequency of specific/prognostic molecular alterations within a cohort of endometrial cancer (EC) women conservatively treated by combined hysteroscopic resection and progestin therapy.

Study Design: We used blocks of formalin-fixed paraffin-embedded tissue from the primary tumors of patients enrolled into the ECCo trial (EudraCT 2010-018581-23) between 2007 and 2016. In order to assign EC resectoscopic specimens to one of four ProMisE subgroups, testing involved sequential assessment of i) immunohistochemistry (IHC) for mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2; ii) sequencing for POLE/POLD1 exonuclease domain mutations (EDMs); iii) p53 IHC.

AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer.

Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness.

Overexpression of ADAR1 into the cytoplasm correlates with a better prognosis of patients with oral squamous cells carcinoma.

Background: ADAR1 is an enzymatic protein, which catalyzes a RNA editing reaction by converting Adenosine to Inosine, and its expression has been found to be dysregulated in many cancer types. The aim of this study was to analyze the expression of ADAR1 in oral squamous cells carcinoma.

Methods: In order to analyze the ADAR1 mRNA expression, data from The Cancer Genome Atlas (TCGA) database were downloaded and analyzed.

Reading in a transparent second language with limited orality: The case of high school students with dyslexia in Latin.

Research has shown that individuals with dyslexia have difficulty in reading not only in their native language but also in a second language (L2). The considered L2, however, has always been a language acquired through exposure to both written and oral forms. The present study examines the case of Italian adolescents reading in Latin as an L2, which is the special case of a dead language with very limited use of orality.

Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression in Oral Squamous Cell Carcinoma.

Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its related gene in oral cancer. Publicly available databases were accessed via Gene Expression Omnibus and Oncomine, in addition raw data from The Cancer Genome Atlas (TCGA) were also obtained in order to analyze the rate of gene mutation, expression and methylation in patients with oral squamous cells carcinoma (OSCC).

Large deletion at the gene locus and search for predictive markers of the presence of a genetic lesion.

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the gene: it has been suggested that early onset of the disease and high Ca levels may predict the presence of a mutation. We searched for large deletions at the locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a gene mutation, clinical/histological diagnosis, age at onset, Ca, PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a gene mutation.

Pleomorphic adenoma of salivary gland and synchronous/metachronous invasive ductal breast cancer: a casual coincidence or a clinical presentation resulting from common genetic events?

Breast and salivary glands have similar morphological and pathological features; however genetic relation between these lesions were not described. In this report we described a small series of biomarkers that developed synchronously or metachronous pleomorphic adenoma of the salivary glands and invasive breast cancer, on which we have tested, by immunohistochemistry, several of bio-markers that may be associated with the pathogenesis of both malignancies. In conclusion, we suggest to better investigate early genetic alterations that could underlie of the synchronous occurrence of these lesions.

Sex Hormone Receptors in Benign and Malignant Salivary Gland Tumors: Prognostic and Predictive Role.

The role of sex hormone receptors in human cancer development and progression has been well documented in numerous studies, as has the success of sex hormone antagonists in the biological therapy of many human tumors. In salivary gland tumors (SGTs), little and conflicting information about the role of the estrogen receptor alpha (ERα), progesterone receptor (PgR) and androgen receptor (AR) has been described and in most cases the use of sex hormone antagonists is not contemplated in clinical practice. In this study, we analyzed a panel of sex hormone receptors that have not been widely investigated in SGTs-ERα, PgR, AR, but also ERβ and GPR30-to define their expression pattern and their prognostic and predictive value in a case series of 69 benign and malignant SGTs.

Accuracy of Fine Needle Cytology in Histological Prediction of Papillary Thyroid Carcinoma Variants: a Prospective Study.

Fine needle cytology (FNC) is a crucial procedure in the preoperative diagnosis of thyroid tumors. Papillary thyroid carcinoma (PTC), in its classic variant (cPTC), is the most common malignant neoplasm of the thyroid. Several histological variants of PTC have been described, each one with its own characteristics and prognosis.

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial.

Background: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds.