Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible factor-1α, and glucose transporter 1 in the development of ovarian clear-cell adenocarcinoma.
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.
Departments of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan.
SourceInternational journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 31:3 2012 May pg 254-63
MeSHAdenocarcinoma, Clear Cell
Gene Expression Regulation, Neoplastic
Glucose Transporter Type 1
Hypoxia-Inducible Factor 1, alpha Subunit
TOR Serine-Threonine Kinases
Tumor Markers, Biological
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't