Clinicopathologic Significance of HNF-1β, AIRD1A, and PIK3CA Expression in Ovarian Clear Cell Carcinoma

Ye, Shuang; Yang, Jiaxin; You, Yan; Cao, Dongyan; Huang, Huifang; Wu, Ming; Chen, Jie; Lang, Jinghe; Shen, Keng

doi:10.1097/md.0000000000003003

Cited by 32 publications

(40 citation statements)

References 23 publications

(32 reference statements)

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“…The prognostic effect of ARID1A loss in O-CCC is debatable, some suggesting a poor prognsosis while others reporting no prognostic impacts 172028. In our study, ARID1A expression status did not have a significant impact on survival.…”

Section: Discussioncontrasting

confidence: 63%

“…HNF1β-overexpression and intact E-cadherin are associated with better prognosis in O-CCC,1727 while the prognostic significance of ERβ expression in O-CCC has not been validated. The prognostic effect of ARID1A loss in O-CCC is debatable, some suggesting a poor prognsosis while others reporting no prognostic impacts 172028.…”

Section: Discussionmentioning

confidence: 99%

“…Positive expression of HNF1β is noted in 90–95% of O-CCCs, contrary to less than 10% of positivity in other epithelium-origin ovarian cancers 15. HNF1β seems to work in the maintenance of E-cadherin expressing epithelial phenotype of O-CCC16 and, thereby, associated with good prognosis 17. However, the functional implications of HNF1β overexpression, particularly in relation to ARID1A loss in O-CCC pathophysiology, have yet to be determined.…”

Section: Introductionmentioning

confidence: 98%

“…In contrast, advanced O-CCCs exhibit heterogeneous behavior, being unpredictable with known clinic-pathological information, such as tumor grade, histologic subtype, stage, etc 19. In this situation, the expressional status of ARID1A and other biomarkers, including ER β, E-cadherin, and HNFβ, may provide further prognostic values 1720. In this study, we analyzed the molecular profiles and prognostic factors of O-CCC, focusing on the different clinical and molecular characteristics of ARID1A-positive and ARID1A-negative tumors.…”

Section: Introductionmentioning

confidence: 99%

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Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

et al. 2017

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PurposeLoss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart.Materials and MethodsSeventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed.ResultsForty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either.ConclusionWe classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

et al. 2017

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“…The interpretation of differentially expressed genes has verified the dysregulated biological functions related to glucose utilization, cell cycle regulation and hormone metabolism, that plays important role in the development of EAOC (60,(68)(69)(70). Transcription factor hepatocyte nuclear factor-1β (HNF1B) was identified as a biomarker of ovarian CCC histology, but not EC, with the hypomethylation of the HNF1B promoter influencing the characteristic biology (60,68,(70)(71)(72)(73)(74)(75). Endometriosis is composed of two subgroups: HNF-1β-positive and -negative cells (71).…”

Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 95%

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

et al. 2018

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In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has diseasespecific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation ('go') and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest ('stop') under oxidative stress conditions. This model underscores a subtype-dependent 'go or stop' dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.

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Prognostic and Clinicopathological Significance of ARID1A in Endometrium‐Related Gynecological Cancers: A Meta‐Analysis

Liu¹,

et al. 2017

J of Cellular Biochemistry

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The tumor suppressor gene, AT Rich Interactive Domain 1A (ARID1A) mutation has been reported in a variety of cancers, especially the endometrium-related gynecological cancers, including the ovarian clear cell carcinoma, ovarian endometrioid carcinoma, and uterine endometrioid carcinoma. However, the prognostic value of ARID1A in endometrium-related gynecological cancers is still inconclusive. Therefore, we performed this meta-analysis to evaluate the clinical significance of ARID1A in endometrium-related gynecological cancers. By systematically searching all the relevant studies from Pubmed, Cochrane Library, and Web of Science up to September 2016, 11 studies with 1,432 patients were included. All the study characteristics and the prognostic data were extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using the fixed-effect or random-effect model. Our results indicated that negative ARID1A expression predicted shorter Progression free survival (PFS, HR, 1.84; 95%CI, 1.32-2.57, P = 0.000) of patients with endometrium related gynecological cancers, especially the patiently with OCCC and the patients in Japan. Besides, a marginal trend towards the same direction was found in the Overall analysis (OS, HR, 1.34; 95%CI, 0.93-1.93, P = 0.112). Furthermore, the significant correlation was achieved between the negative ARID1A expression and the FIGO stage of endometrium-related gynecological cancers, but not the other characteristics. J. Cell. Biochem. 118: 4517-4525, 2017. © 2017 Wiley Periodicals, Inc.

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Clinicopathologic Significance of HNF-1β, AIRD1A, and PIK3CA Expression in Ovarian Clear Cell Carcinoma

Abstract: Supplemental Digital Content is available in the text

Cited by 32 publications

References 23 publications

Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

Prognostic and Clinicopathological Significance of ARID1A in Endometrium‐Related Gynecological Cancers: A Meta‐Analysis

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