Aberrant Expression of the Mammalian Target of Rapamycin, Hypoxia-inducible Factor-1α, and Glucose Transporter 1 in the Development of Ovarian Clear-cell Adenocarcinoma

Masafumi Kato, Sohei Yamamoto, Masashi Takano, Osamu Matsubara, Kenichi Furuya
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2012 · vol. 31(3) , pp. 254–263 · doi:10.1097/pgp.0b013e318237d66c · PMID:22498943 · W2327842639
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Expression of p-mTOR, HIF-1α, and Glut1 increases with atypia in precursor lesions and cumulatively occurs during the development of ovarian clear-cell adenocarcinoma.

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Abstract

Ovarian clear-cell adenocarcinoma (CCA) is known to be a type of cancer in humans with a high frequency of expression of the mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 (HIF-1), and glucose transporter 1 (Glut1). In this study, we aimed to determine how these alterations contribute to tumor development of CCAs. Immunohistochemical expressions of phosphorylated-mTOR (p-mTOR), HIF-1α, and Glut1 were analyzed in 36 CCAs and 60 coexistent putative precursor lesions: 19 nonatypical and 16 atypical endometriotic lesions, and 11 benign and 14 borderline clear-cell adenofibroma (CCAF) components. Twenty-one cases with solitary endometriosis were also examined. The frequencies of immunopositivity for p-mTOR (in cytoplasm or nucleus), HIF-1α (in nucleus), and Glut1 increased in accordance with higher cytological atypia in the putative precursors: 58%, 5%, and 16% in the nonatypical endometriosis; 63%, 37%, and 50% in the atypical endometriosis; 77%, 95%, and 95% in the endometriosis-associated CCAs; 27%, 0%, and 0% in the benign-CCAF components; 64%, 79%, and 43% in the borderline CCAF components; and 71%, 100%, and 93% in the CCAF-associated CCAs, respectively. p-mTOR, HIF-1α (in the nucleus), and Glut1 were positive in 10%, 5%, and 19% of the solitary endometriosis, respectively. In the putative precursor lesions coexisting with CCA, a strong correlation in the expression between p-mTOR and HIF-1α and between HIF-1α and Glut1 was identified. Expressions of p-mTOR, HIF-1α, and Glut1 have already been evident in the putative precursor lesions of CCA, and these alterations cumulatively occur in the development of ovarian CCA.

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Condition tags

endometriosis

MeSH descriptors

Adenocarcinoma, Clear Cell Glucose Transporter Type 1 Hypoxia-Inducible Factor 1, alpha Subunit Ovarian Neoplasms TOR Serine-Threonine Kinases Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenofibroma Adenofibroma Adenofibroma Biomarkers, Tumor Biomarkers, Tumor Endometriosis Endometriosis Endometriosis Female Gene Expression Regulation, Neoplastic Glucose Transporter Type 1 Humans Hypoxia-Inducible Factor 1, alpha Subunit

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