Genomic and Molecular Abnormalities in Gynecologic Clear Cell Carcinoma

Gynecologic clear cell carcinoma is a rare histology, accounting for ~5% of all ovarian and endometrial cancers in the United States. Compared to other types of gynecologic cancer, they are generally less responsive to standard therapy and have an overall worse prognosis. In addition, mounting evidence suggests that the landscape of genetic and molecular abnormalities observed in these tumors is distinct from other cancers that arise from the same sites of origin. On a molecular level, these tumors characteristically display upregulation of the PI3K-AKT-mTOR and RAS-RAF-MAPK signaling axes, frequent loss of ARID1a, and overexpression of MDM2. Evidence also suggests that these tumors are more likely to express programmed death ligand 1 or demonstrate microsatellite instability than other gynecologic cancers. Despite these important differences, there has been relatively little investigation into histology-specific treatment of clear cell gynecologic cancers, representing an opportunity for new drug development. In this article, we review the unique genetic and molecular features of gynecologic clear cell cancers with an emphasis on potential therapeutic targets. The results of completed studies of treatment for clear cell carcinoma are also presented. We conclude with a discussion of ongoing clinical trials and potential avenues for future study.
Source: American Journal of Clinical Oncology - Category: Cancer & Oncology Tags: Review Article Source Type: research

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Authors: Yamagami W, Nagase S, Takahashi F, Ino K, Hachisuga T, Mikami M, Enomoto T, Katabuchi H, Aoki D Abstract OBJECTIVE: International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and peritoneal cancers was revised in 2014. The aim of this study is to clarify whether the revised FIGO2014 staging reflects the prognosis of patients with ovarian cancer by histological type in Japan. METHODS: We extracted 9,747 patients who were diagnosed with ovarian cancer since 2004 until 2008 and who could be classified into appropriate stages from the Gynecologic Cancer Registry of Ja...
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
In this study, we have analyzed a prospective cohort of 502 early-stage OCs to investigate their frequency, immunohistochemical characteristics, and survival of the 5 main histologic types. Histotype was assigned according to not only the morphologic features but also according to the expression pattern of WT1, p53, Napsin A, and progesterone receptors. In addition, an extended panel including p16, β-catenin, HER2, Arid1A, HINF1B, CK7, CDX2, and CK20 was used to refine the diagnosis in difficult cases. In this series, the frequency of the 5 major histologic types was as follows: endometrioid carcinoma, 32.7%; clear ce...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research
CONCLUSIONS: Our data show that MSI is present in a substantial proportion of endometrioid ovarian cancers but can also occur in other tumor subtypes. MMR deficiency/MSI typically involves the entire tumor mass, suggesting that MMR inactivation occurs early in tumorigenesis in a subset of ovarian cancers. PMID: 31924330 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
ConclusionsEndometriosis is not independently associated with the prognosis of OEC and OCCC among young patients. The intrinsic relationship between endometriosis and ovarian cancer warrants further investigation.
Source: European Journal of Surgical Oncology (EJSO) - Category: Surgery Source Type: research
ConclusionsPositive findings in abdominopelvic washing cytology is rare. The majority of the positive cases were from müllerian origins, with ovary and uterus as the most common sites. Endometrial adenocarcinoma, endometrioid type and ovarian high-grade serous carcinoma were the most common tumor types. Knowing prior history of malignancy, morphologic comparison with concurrent surgical cases, and performing ancillary studies are keys to improve diagnostic accuracy of abdominopelvic washings.
Source: Journal of the American Society of Cytopathology - Category: Cytology Source Type: research
ConclusionsPositive findings in abdominopelvic washing cytology is rare. The majority of the positive cases were from müllerian origins with ovary and uterus as the most common sites. Endometrial adenocarcinoma, endometrioid type and ovarian high grade serous carcinoma were the most common tumor types. Knowing prior history of malignancy, morphological comparison with concurrent surgical cases and performing ancillary studies are keys to improve diagnostic accuracy of abdominopelvic washings.
Source: Journal of the American Society of Cytopathology - Category: Cytology Source Type: research
ConclusionsTAS-117 had a manageable safety profile with clinical antitumor activity in pts with advanced solid tumors. Further investigation of the drug in a combination therapy is in preparation.Clinical trial identificationJapicCTI-152780.Legal entity responsible for the studyTaiho Pharmaceutical Co., Ltd.FundingHas not received any funding.DisclosureS. Takahashi: Honoraria (self), Research grant / Funding (self): Eisai; Honoraria (self): Bristol-Myers-Squibb; Honoraria (self), Research grant / Funding (self): Taiho; Honoraria (self): Bayer; Research grant / Funding (self): MSD; Research grant / Funding (self): Astrazene...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractPurposeProstaglandin-mediated inflammatory reactions play a major role in different cancers. Recently, it has been observed that prostaglandin E2-receptor 3 (EP3) might be an independent prognostic factor for overall survival in cervical and endometrial cancer. The role of EP3 expression in ovarian cancer is currently unknown.MethodsEP3 expression was analyzed by immunohistochemistry in 156 patient samples using the IR-scoring system. Expression levels were correlated with clinical and pathological parameters and with overall survival (OS) to assess for prognostic relevance. Data analysis was performed using Spearm...
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
r A Abstract PURPOSE: Prostaglandin-mediated inflammatory reactions play a major role in different cancers. Recently, it has been observed that prostaglandin E2-receptor 3 (EP3) might be an independent prognostic factor for overall survival in cervical and endometrial cancer. The role of EP3 expression in ovarian cancer is currently unknown. METHODS: EP3 expression was analyzed by immunohistochemistry in 156 patient samples using the IR-scoring system. Expression levels were correlated with clinical and pathological parameters and with overall survival (OS) to assess for prognostic relevance. Data analysis wa...
Source: Clin Med Res - Category: Research Authors: Tags: J Cancer Res Clin Oncol Source Type: research
GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. However, expression has also been described in more common malignancies of gynecologic tract including ovarian, endometrial, and cervical carcinomas. Data on the distribution of GATA3 expression in gynecologic malignancies is somewhat limited, particularly across different histologic subtypes of ovarian, endometrial, and cervical carcinomas. To assess the rates of GATA...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: Pathology of the Lower Genital Tract: Original Article Source Type: research
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