The Effect of Histological Subtypes on Outcomes of Stage IV Epithelial Ovarian Cancer
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Abstract:
Introduction: To examined survival outcome by histological subtypes in de novo stage IV epithelial ovarian cancer (EOC). Methods: Between 2004 and 2015, patients with stage IV EOC were included using the Surveillance, Epidemiology, and End Results program. The effects of histological subtypes on overall survival (OS) were assessed using Kaplan-Meier and multivariable Cox regression analyses. Results: We identified 5,953 patients including 5,351 (89.9%), 249 (4.2%), 145 (2.4%), and 208 (3.4%) patients with high-grade serous, endometrioid, mucinous, and clear cell subtypes, respectively. The 5-year OS rates were 28.1, 38.6, 14.2, and 18.8% in patients with high-grade serous, endometrioid, mucinous, and 18.8% clear cell subtypes, respectively, (p < 0.001). Multivariate analyses indicated that histological subtype was an independent predictor of OS. Using the high-grade serous subtype as a reference, OS was comparable for the endometrioid subtype (hazard ratio (HR) 0.915, 95% confidence interval) (CI 0.772-1.085, p = 0.305), but significantly lower for mucinous (HR 3.292, 95% CI 2.701-4.011, p < 0.001) and clear cell subtypes (HR 1.820, 95% CI 1.546-2.141, p < 0.001). Patients with no residual tumor had better OS in the high-grade serous and endometrioid subtypes compared to patients with residual tumors. However, the residual tumor size was not a prognostic factor for OS in mucinous and clear cell carcinoma. Conclusions: Our study suggest a markedly mortality rate in patients with stage IV mucinous and clear cell carcinoma, but better survival in patients with high-grade serous and endometrioid subtypes. Aggressive radical surgery to leave no residual disease would improve survival for high-grade serous and endometrioid carcinoma. More studies are needed to assess the value of aggressive radical surgery in patients with mucinous and clear cell subtypes.Keywords:
Clear cell carcinoma
Serous carcinoma
There are several morphologic types of ovarian carcinoma. It has been shown that p16 is overexpressed in high-grade serous carcinoma but there has been little detailed comparison of p16 expression in the common types of ovarian carcinoma. The aim of this study was to compare p16 expression in ovarian carcinomas of serous, endometrioid, clear cell, and mucinous type with a view to ascertaining whether high expression in a primary ovarian carcinoma is specific for a serous neoplasm. We included problematic cases, which are difficult to type, such as poorly differentiated and undifferentiated carcinomas and serous carcinomas with clear cells. In these problematic groups, we compared p16 expression with that of WT1, which is known to be relatively specific for a serous phenotype. Cases of ovarian high-grade serous carcinoma (n=38), endometrioid carcinoma (n=15), clear cell carcinoma (n=12), and mucinous carcinoma (n=10) were stained with p16. Cases were scored both with respect to distribution of immunoreactivity (0–5) and intensity (0–3). An immunohistochemical composite score was also calculated (0–15) by multiplying the distribution and intensity scores. Serous carcinomas typically exhibited high p16 expression; there was statistically significant higher p16 expression in serous carcinomas compared with the other morphologic types. There was high p16 and WT1 expression in most undifferentiated carcinomas and in serous carcinomas with clear cells, suggesting that these represent variants of serous carcinoma. We have demonstrated that p16 is highly expressed in high-grade serous and undifferentiated carcinomas compared with other morphologic types of ovarian carcinoma. This may be useful, in conjunction with WT1, in the classification of problematic neoplasms. p16 may be involved in the pathogenesis of high-grade ovarian serous carcinomas, possibly through inactivation of retinoblastoma protein.
Serous carcinoma
Clear cell carcinoma
Cystadenocarcinoma
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Serous carcinoma
Clear cell carcinoma
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This study was designed to analyze certain clinicopathological features and the profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression of clear cell carcinoma of the endometrium and to determine whether the pathogenesis of clear cell carcinoma can be accommodated by a dualistic model of endometrial carcinogenesis. In this model, endometrioid carcinoma develops from endometrial hyperplasia under unopposed estrogenic stimulation, and serous carcinoma develops in atrophic endometrium from a putative precursor lesion designated endometrial intraepithelial carcinoma (EIC). Twenty-one clear cell carcinomas of the endometrium were analyzed and compared with 77 endometrioid carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a distinctive immunoprofile characterized by immunonegativity for ER and PR, low immunoreactivity for p53, and a high Ki-67 proliferation index. ER, PR, and Ki-67 expression were similar to serous carcinoma, but p53 expression was significantly lower in clear cell carcinoma (P < .05). ER and PR expression were significantly lower, and the Ki-67 proliferation index was significantly higher in clear cell carcinoma compared with endometrioid carcinomas (P < .05). p53 expression tended to be higher in clear cell carcinoma compared with endometrioid carcinoma, but the difference was not statistically significant. In contrast to endometrioid carcinoma, clear cell carcinoma was rarely associated with endometrial hyperplasia and serous carcinoma was not. Subdividing clear cell carcinoma morphologically into one that resembled serous carcinoma (clear cell carcinoma with serous features) and another that did not (typical clear cell carcinoma) showed that clear cell carcinoma with serous features had a higher Ki-67 proliferation index than typical clear cell carcinoma, although expression of ER, PR, and p53 were similar. Clear cell carcinoma with serous features was associated with EIC in 50% and was not associated with endometrial hyperplasia. In contrast, typical clear cell carcinoma was associated with endometrial hyperplasia in 40% and was not associated with EIC. In summary, this study provides evidence that clear cell carcinoma of the endometrium, like serous carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In contrast to serous carcinoma, strong p53 expression occurred less frequently in clear cell carcinoma and predominantly in clear cell carcinoma with serous features. The findings suggest that the molecular events that underlie the development of clear cell carcinoma differ from those of endometrioid and serous carcinoma.
Clear cell carcinoma
Serous carcinoma
Endometrial hyperplasia
Atypical Hyperplasia
Progesterone receptor
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Serous carcinoma and clear cell carcinomas account for 10% and 3% of endometrial cancers but are responsible for 39% and 8% of cancer deaths, respectively. In this study, we aimed to compare serous carcinoma and clear cell carcinoma regarding the surgico-pathologic and clinical characteristics, and survival, and to detect factors that affected recurrence and survival.We retrospectively analyzed patients with clear cell and serous endometrial cancer who underwent surgery between January 1993 and December 2013 in our clinic. We used Kaplan-Meier estimator to analyze survival.The tumor type in 49 patients was clear cell carcinomas and was serous uterine carcinoma in 51 patients. Advanced stage (stage III and IV) disease was present in 42% of the patients in the clear cell group, whereas this rate was 62% in the serous group (p=0.044). Lymph node metastasis was detected in 37% of the patients with clear cell carcinomas and 51% of the patients with serous carcinoma (p=0.17). The adjuvant therapies used did not differ significantly between the groups (p=0.192). The groups had similar recurrence patterns. Five-year progression-free survival and the 5-year overall survival were 60.6% and 85.8%, 45.5% and 67.8% in the patients with clear cell carcinomas and serous tumor, respectively.With the exception that more advanced stages were observed in patients with serous carcinoma endometrial cancers at presentation, the surgico-pathologic features, recurrence rates and patterns, and survival rates did not differ significantly between the groups with clear cell carcinoma and serous carcinoma endometrial cancers.
Serous carcinoma
Clear cell carcinoma
Serous membrane
Adjuvant Therapy
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Serous carcinoma
Clear cell carcinoma
Cystadenocarcinoma
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Clear Cell Adenocarcinoma
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Neoadjuvant chemotherapy followed by interval debulking has become an alternative treatment option for patients with advanced-stage ovarian cancer. The effects of chemotherapy on the histologic features of the tumor have not been well described for ovarian carcinoma, especially related to changes that significantly alter the appearance of the tumor. In this study, we describe a case of ovarian serous carcinoma status-post neoadjuvant chemotherapy that showed exuberant clear cell/foamy change. This unusual morphology raised the possibility of a mixed epithelial carcinoma or a secondary malignancy. Immunohistochemical stains were performed to help distinguish whether the tumor was a serous carcinoma with chemotherapy-induced clear cell change or a distinct clear cell carcinoma of ovarian or extraovarian origin. The clear cell and conventional serous components showed diffuse positivity for CK7, CA125, and ER; however, only the clear cell component was positive for hepatocyte nuclear factor-1beta and only the conventional serous component was positive for WT1. Although there was a slight discrepancy in the staining patterns, given the lack of other typical histologic features of clear cell carcinoma, the unusual clear cell morphology was most likely the result of chemotherapy-induced changes.
Serous carcinoma
Clear cell carcinoma
Debulking
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Serous carcinoma
Clear cell carcinoma
Gynecologic oncology
Not Otherwise Specified
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Serous carcinoma
Clear cell carcinoma
Ovarian carcinomas
Cystadenocarcinoma
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