Epithelial ovarian cancer (EOC) consists of 5 major histotypeshigh-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade ...serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin–stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs.
Atypical endometriosis (AE) is thought to be a precursor lesion to the ovarian cancer subtypes associated with endometriosis, namely, endometrioid and clear cell carcinomas. ARID1A encodes a nuclear ...protein (BAF250a) governing chromatin remodeling, and mutations in ARID1A have been found in 30% to 50% of clear cell and endometrioid ovarian cancers. As BAF250a expression loss by immunohistochemistry (IHC) has been documented in the endometriosis precursor lesions closely associated with these ovarian cancers subtypes, our goal was to further study the association between BAF250a expression in cases of AE with and without an associated cancer.
Three separate databases were screened for suspected cases of AE. Based on a detailed review of the pathology reports, we selected cases likely to contain AE for slide review. After slide review, tissue blocks were recalled to perform IHC for BAF250a in the associated cancer, AE, or typical endometriosis when present.
There were 35 cases of endometriosis-associated cancer and 8 cases of AE not associated with cancer. Atypical endometriosis was found on pathology review in 23 endometriosis-associated cancer cases (66%). In the 35 cancer cases, BAF250a IHC showed loss of expression in 14 cases. Atypical endometriosis was present in 10 of these cases, 6 of which showed BAF250a loss (60%). BAF250a loss was not observed in the 8 cases of AE not associated with cancer or in the contiguous AE of 13 cases, whereby BAF250a expression was retained in the associated cancer.
BAF250a loss in AE is consistently associated with the development of BAF250a-negative endometriosis-associated cancers and appears to be an early event in most of these cases. This research provides additional evidence that in the absence of cancer, BAF250a expression should be evaluated as a biomarker of cancer risk in patients diagnosed with AE.
Abstract Objective Meta-analyses report a null association between recent alcohol consumption and ovarian cancer risk. However, because few studies investigated different types of alcohol over adult ...ages, we investigated adult lifetime and type (beer, wine, spirits) of consumption and risk. Methods Consumption after age 20 years was ascertained in 1144 invasive epithelial ovarian cancer cases and 2513 controls in a population-based case–control study (Alberta and British Columbia, Canada, 2001–2012). Non-drinkers consumed any types of alcohol < 12 times per year on average. Logistic regression was use to estimate adjusted odds ratios aOR and 95% confidence intervals CIs. Results Wine consumption was associated with a risk reduction (aOR = 0.67, 95% CI: 0.50–0.88) relative to non-drinkers, but not beer (aOR = 1.06, 95% CI: 0.71–1.58) or spirits (aOR = 0.98, 95% CI: 0.69–1.39). The reduced risk was stronger for exclusive red wine drinkers (aOR = 0.44, 95% CI: 0.19–0.92) than white wine drinkers (aOR = 0.79, 95% CI: 0.46–1.34), although most women drank both types of wine. Risk decreased with increasing cumulative consumption of any wine (P-trend < 0.05) and was evident for the serous histotype. Wine consumption initiated prior to age 50 was associated with a risk reduction (e.g., at 40–49 years, aOR = 0.58, 95% CI: 0.42–0.78), but not drinking initiated after 50 years of age. For any type, level, or age at initiation of alcohol consumption, we found no increased risks. Conclusions For the moderate consumption in this study, higher levels of wine consumption were generally associated with risk reductions; reductions may be stronger for red wine. Our results suggest that alcohol consumption that is guideline concordant will not increase epithelial ovarian cancer risk.
When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes ...to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL) could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer.
In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3)) and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1)) correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors HR: 2.314 (95% CI 1.049-5.106); p = 0.0377. Patients with high vascular endothelial growth factor (VEGF) expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors HR: 2.522 (95% CI 1.097-5.799); p = 0.0294.
Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.
Differentiated vulvar intrapeithelial neoplasia (dVIN) is an human papillomavirus (HPV)-independent precursor of squamous cell carcinoma (SCC), and the aim of this study was to better characterize ...its natural history. Cases of dVIN were identified from the pathology archives. Outcomes of patients with dVIN only, without associated invasive SCC, were compared with a cohort of patients with high-grade squamous intraepithelial lesion HSIL(VIN3). Eighteen patients diagnosed with dVIN with adjacent invasive SCC (SCC/dVIN) and 7 patients with dVIN only, without invasive carcinoma, were identified. Mean age in both cohorts was 75 yr. All lesions but 1 were unifocal. In 35% of SCC/dVIN cases the surgical resection margins were positive for SCC, with 75% and 60% having margins positive for dVIN in the SCC/dVIN and dVIN-only cohorts, respectively. In total, 23/25 women with dVIN only or dVIN/SCC, for whom there was follow-up information, experienced either progression to or recurrence of invasive SCC, respectively, at a median of 1.1 yr, including all but 1 case of dVIN only, where the median time of progression to invasive SCC was 1.9 yr. A total of 22/25 women died of disease with a median overall survival of 3.4 yr. The outcome (i.e. progression to invasive carcinoma) of patients with dVIN only was significantly worse than that of a comparison group of 18 patients with HSIL(VIN3) (progression-free survival log-rank, P<0.001; disease-specific survival, P=0.04; overall survival, P=0.01). Six of 7 patients with dVIN only developed invasive carcinoma on follow-up, compared with 0 of 18 patients with HSIL(VIN3). The diagnosis of dVIN indicates the presence of a high-risk human papillomavirus-negative precursor of invasive SCC. These patients are likely to progress to invasive carcinoma over a relatively short period, at which point their prognosis is guarded.
Epithelial ovarian cancer consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC) and low-grade serous ...(LGSC). Each can have a broad spectrum of morphological appearances, and one histotype can closely mimic histopathological features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present based on routine histopathological assessment, histotype carcinoma diagnoses (3–11%), however recent immunohistochemical studies identifying histotype specific markers and allowing more refined histotype diagnoses suggests a much lower incidence. We reviewed hematoxylin and eosin stained slides from 871 cases of epithelial ovarian cancer and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed epithelial ovarian cancers, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC and 4 other combinations. We interrogated the molecular differences between the different components of each case using immunohistochemistry, gene expression and hotspot sequencing analyses. Immunohistochemical data alone suggested 9 of the 22 cases were not mixed tumors as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphological mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. Based on these results, true mixed carcinomas with both morphological and molecular support for the presence of more than one histotype within a given tumor represent less than 1% of epithelial ovarian cancers.
Background When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that ...contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL) could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. Methodology and Principal Findings In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3)) and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1)) correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors HR: 2.314 (95% CI 1.049-5.106); p = 0.0377. Patients with high vascular endothelial growth factor (VEGF) expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors HR: 2.522 (95% CI 1.097-5.799); p = 0.0294. Significance Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.
Objectives: Violence against women is a global public health problem. Although there has been much research done on violence against women, there are few studies that provide the current scientific ...production. Methods: In this study, bibliometric analysis has been used to evaluate the 1984 documents from 1986 to 2020 based on the Scopus database. These documents were analyzed quantitatively by the Bibliometric R Package and the VOS viewer software. In addition, the 20 top-cited papers were analyzed qualitatively. Results: The research findings show that the United States is a leader in this field with the most highly cited articles and also the greatest number of publications followed by the United Kingdom, Canada, Australia, and South Africa. A total of 1984 documents were collected from the Scopus database and were analyzed in the Bibliometric R Research Package and the VOSviewer software. The results demonstrated that the average citations per year for each document were 23.39% and the annual scientific production growth rate was 16.86%. The keywords analysis indicates that most articles focus on “sexual violence”, “sexual assault”, “intimate partner violence”, “violence against women”, “sexual abuse”, “domestic violence”, “child sexual abuse”, “prevention”, and “rape.” Sources such as the “Journal of Interpersonal Violence”, “Journal of Violence Against Woman”, “Journal of Violence and Victims”, “Psychology of Women Quarterly”, “Journal of Adolescent Health”, “Journal of Consulting and Clinical Psychology”, “American Journal of Public Health”, “Journal of Consulting and Clinical Psychology”, and “American Journal of Public Health”, and “The Lancet” are the top most productive in this field. Discussion: Examining the articles showed that the vast majority of women have experienced verbal, sexual, intimate partner violence, cyber harassment, and so on.
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