Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible factor-1α, and glucose transporter 1 in the development of ovarian clear-cell adenocarcinoma.

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.

• Authors: Masafumi Kato, Sohei Yamamoto, Masashi Takano, Osamu Matsubara, Kenichi Furuya
• Journal: International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists (Int J Gynecol Pathol) Vol. 31 Issue 3 Pg. 254-63 (May 2012) ISSN: 1538-7151 [Electronic] United States
• PMID: 22498943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Glucose Transporter Type 1
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• SLC2A1 protein, human
• MTOR protein, human
• TOR Serine-Threonine Kinases

Topics

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