Toward an understanding of the pathophysiology of clear cell carcinoma of the ovary (Review)

Abstract

Endometriosis-associated ovarian cancers demonstrate substantial morphological and genetic diversity. The transcription factor, hepatocyte nuclear factor (HNF)-1β, may be one of several key genes involved in the identity of ovarian clear cell carcinoma (CCC). The present study reviews a considerably expanded set of HNF-1β-associated genes and proteins that determine the pathophysiology of CCC. The current literature was reviewed by searching MEDLINE/PubMed. Functional interpretations of gene expression profiling in CCC are provided. Several important CCC-related genes overlap with those known to be regulated by the upregulation of HNF-1β expression, along with a lack of estrogen receptor (ER) expression. Furthermore, the genetic expression pattern in CCC resembles that of the Arias-Stella reaction, decidualization and placentation. HNF-1β regulates a subset of progesterone target genes. HNF-1β may also act as a modulator of female reproduction, playing a role in endometrial regeneration, differentiation, decidualization, glycogen synthesis, detoxification, cell cycle regulation, implantation, uterine receptivity and a successful pregnancy. In conclusion, the present study focused on reviewing the aberrant expression of CCC-specific genes and provided an update on the pathological implications and molecular functions of well-characterized CCC-specific genes.

Novel biomarker candidates for the diagnosis of ovarian clear cell carcinoma

“…This transcription factor plays a role in endometrial regeneration, differentiation, decidualization, glycogen synthesis, detoxification, cell cycle regulation, implantation, uterine receptivity and a successful pregnancy (7). Furthermore, HNF1B regulates a subset of progesterone target genes and may act as a modulator of female reproduction (7). The immunohistochemical study revealed that the positive HNF1B staining was a frequent finding in clear cell carcinoma.…”

“…HNF1B induces cell cycle arrest and stimulates an anti-apoptotic response to oxidative stress-induced DNA damage (9). Therefore, elucidating the detailed association between HNF1B upregulation and the acquisition of cell cycle regulation under conditions of oxidative stress may improve understanding of the mechanisms used to repair DNA damage (7). A previous study identified the role of the HNF1B-mediated signaling pathway in a fail-safe mechanism for the oxidative stress-induced DNA damage response (10).…”

“…The HNF1B protein binds to DNA as a member of the homeodomain-containing superfamily of transcription factors. This transcription factor plays a role in endometrial regeneration, differentiation, decidualization, glycogen synthesis, detoxification, cell cycle regulation, implantation, uterine receptivity and a successful pregnancy (7). Furthermore, HNF1B regulates a subset of progesterone target genes and may act as a modulator of female reproduction (7).…”

Disruption of Glycogen Utilization Markedly Improves the Efficacy of Carboplatin against Preclinical Models of Clear Cell Ovarian Carcinoma

“…Ovarian clear cell carcinoma (OCC) is the second most common type of epithelial ovarian cancer (EOC), comprising 5-25% of all ovarian cancers, depending on ethnicity [1,2]. Patients are managed for the other EOC histotypes with cytoreductive surgery and chemotherapy [3,4]. However, the platinum-based chemotherapy that is applied to other histotypes, such as the more common high-grade serous ovarian carcinoma (HGSOC), is often ineffective for OCC [4,5], with recurrent and high-stage disease particularly resistant to this treatment [6][7][8][9].…”

“…Patients are managed for the other EOC histotypes with cytoreductive surgery and chemotherapy [3,4]. However, the platinum-based chemotherapy that is applied to other histotypes, such as the more common high-grade serous ovarian carcinoma (HGSOC), is often ineffective for OCC [4,5], with recurrent and high-stage disease particularly resistant to this treatment [6][7][8][9]. The paucity of treatment options is reflected in the poorer prognosis of OCC compared to other EOC histotypes [7,10].…”