Cyclo-oxygenase-2 (Cox-2) expression and resistance to platinum versus platinum/paclitaxel containing chemotherapy in advanced ovarian cancer

BACKGROUND: Cyclo-oxygenase-2 (COX-2), the key enzyme in the conversion of arachidonic acid to prostaglandins, is involved in critical steps of tumor onset and progression, and is a strong predictor of chemotherapy resistance and poor outcome in advanced ovarian cancer. To our knowledge, no data has been reported until now about the association between COX-2 status and response to different chemotherapy regimens. METHODS: A retrospective study was performed to investigate the association of COX-2 with outcome and response to platinum versus platinum/paclitaxel in 68 primary ovarian cancer. COX-2 immunoreaction was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against COX-2. RESULTS: In the overall series, COX-2 positivity was found in a statistically significant higher percentage of not responding cases than in patients responding to chemotherapy (n = 15/21; 71.4% versus n = 17/47; 36.1%; p value = 0.0072). A higher percentage of COX-2 positivity was found in patients unresponsive (n = 11/13; 84.6%) versus patients responsive to platinum-based chemotherapy (n = 9/26; 34.6%). In cases administered platinum/paclitaxel, COX-2 positivity was found in 4 out of 8 (50%) of un responsive versus 8 out of 21 (38.1%) of responsive cases. Logistic regression analysis of parameters likely to affect response to treatment resulted in a p value = 0.17 for the interaction COX-2/type of treatment. CONCLUSION: Although these findings need to be confirmed in a larger series, our study suggests a possible indication that there is a difference in the influence of COX-2 on response depending on treatment regimen

TCGA Molecular Subgroups in Endometrial Undifferentiated/Dedifferentiated Carcinoma

We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer: microsatellite-instable/hypermutated (MSI), POLE-mutant/ultramutated (POLE), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-abnormal (p53abn), through a systematic review and meta-analysis. Electronic databases were searched from January 2013 to July 2019 for studies assessing the TCGA classification in endometrial UDC/DDC series. Pooled prevalence of each TCGA subgroup on the total UDC/DDCs was calculated. Three studies with 73 patients were included. Pooled prevalence of the TCGA subgroups were: 12.4% for the POLE subgroup, 44% for the MSI subgroup, 18.6% for the p53abn subgroup, 25% for the p53wt group. All TCGA groups are represented in UDC/DDC, with a predominance of the MSI group, indicating a biological heterogeneity. Hypermutated/ultramutated cancers constitute the majority of UDC/DDC, suggesting a crucial difference with other high-risk histologies of endometrial carcinoma

Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases

We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies

Impact of adenomyosis on the prognosis of patients with endometrial cancer

Background Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear. Objective To assess the prognostic value of coexistent adenomyosis in patients with EC. Methods A systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable. Results Three studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis. Conclusion In EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies

The Vulvar Immunohistochemical Panel (VIP) Project:Molecular Profiles of Vulvar Squamous Cell Carcinoma

Introduction: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expressio

Melanocyte Colonization and Pigmentation of Breast Carcinoma: Description of Two Pathological Cases and Review of Literature

Colonization of breast carcinoma by non-neoplastic melanocytes of epidermal origin was first described by Azzopardi and Eusebi in 1977. We herein report two cases on the exceptional clinical and pathological features of this phenomenon in a 66-year-old and a 51-year-old patients. The pathogenesis is not fully understood, but a disrupted basement membrane and the role of tumoral growth factors are considered essential

Biomarker characterization in endometrial cancer in Europe: first survey data analysis from 69 pathological academic and hospital labs

Introduction. Endometrial carcinoma (EC) is the commonest gynecological cancer affecting women in Western populations. To predict patient risk, the 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract stressed the importance of integrated histo-molecular classification of the disease. This survey analysis poses attention on the most frequently used immunohistochemical and molecular markers adopted in daily categorization of ECs in European laboratories. Methods. We analyzed data collected through questionnaires administered to 40 Italian, 20 Spanish, 3 Swiss and 6 United Kingdom (UK) laboratories. We collected information regarding daily practice in EC evaluation, specifically concerning mismatch repair status (MMR) and microsatellite instability (MSI). Summary and descriptive statistical analyses were carried out to evaluate the current practice of each laboratory. Results. The results show that MMR status is mainly evaluated by using immunohistochemistry (IHC) on most EC samples. The most frequent approach for the analysis of MMR status is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular methods is uncommon but useful as a supplemental tool in specific conditions. MLH1 promoter hypermethylation and BRAF V600 mutations analysis are performed in case of negative expression of MLH1/PMS2. Other markers (mainly p53 followed by POLE and PTEN) are investigated in particular in Spain and Switzerland in a consistent number of cases. Conclusion. Guidelines consultation and standardization of laboratory procedures are efficient means for EC prognostic risk stratification and improving the quality of care

Chromosome 9p deletion syndrome and sex reversal: novel findings and redefinition of the critically deleted regions

Deletions of the short arm of chromosome 9 are associated with two distinct clinical entities. Small telomeric 9p24.3 deletions cause genital anomalies in male subjects, ranging from disorder of gonadal sex to genital differentiation anomalies, while large terminal or interstitial deletions result in 9p-malformation syndrome phenotype. The critical region for non-syndromic 46,XY sex reversal was assigned to a 1 Mb interval of chromosome 9p, extending from the telomere to the DMRT genes cluster. The 9p-syndrome was assigned to bands 9p22.3p24.1, but a phenotypic map has not been established for this condition, probably because of the lack of detailed molecular and/or phenotypic characterization, as well as frequent involvement of additional chromosome rearrangements. Here, we describe a unique patient with a small isolated 9p terminal deletion, characterized by array-CGH and FISH, who shows a complex phenotype with multiple physical anomalies, resembling the 9p-syndrome, disorder of sex development with gonadoblastoma, congenital heart defect and epilepsy. The observed deletion includes the 46,XY sex-reversal critical region, excluding the region so far associated with the 9p-syndrome. Genotype-phenotype correlations are tentatively established comparing our patient to seven other previously reported males with isolated terminal 9p deletions, finely defined at a molecular level. Our observations expand the 9p deletion clinical spectrum, and add significantly to the definition of a 9p-syndrome critical region

Recurrence in skeletal muscle from squamous cell carcinoma of the uterine cervix: a case report and review of the literature

BACKGROUND: The occurrence of skeletal muscle metastases is a very rare event. Only two cases of late skeletal muscle recurrence from cervical cancer have been documented until now. CASE PRESENTATION: A 38-year old patient, submitted to radical hysterectomy and pelvic lymphadenectomy for a squamous FIGO stage IB1 cervical carcinoma, presented after 76 months with a palpable, and painless swelling on the left hemithorax. MRI showed a nodule located in the context of the intercostal muscles. Pathology revealed the presence of metastasis of squamous cell carcinoma of similar morphology as the primary. On the basis of FDG-PET findings, which excluded other sites of disease, surgical excision of the lesion was performed. The patient was triaged to chemotherapy plus external radiotherapy. CONCLUSION: A case of skeletal muscle recurrence from cervical cancer after a very long interval from primary diagnosis is reported. Muscular pain or weakness, or just a palpable mass in a patient with a history of cancer has always to raise the suspicion of muscle metastasis