Expression of platelet-derived growth factors and their receptors in ovarian clear-cell carcinoma and its putative precursors.
Recent studies have shown that platelet-derived growth factors and their receptors are frequently co-expressed in ovarian cancers. Herein, we investigated the role of the platelet-derived growth factor pathway in the development of ovarian clear-cell adenocarcinoma, a highly chemoresistant form of ovarian cancer. Immunohistochemical expression of platelet-derived growth factor receptor-alpha and receptor-beta, platelet-derived growth factor A-chain and B-chain was examined in 31 cases of clear-cell adenocarcinoma and 56 coexisting putative precursor lesions: 17 non-atypical and 19 atypical endometrioses, and 10 non-atypical and 10 atypical clear-cell adenofibroma components. Twenty-one solitary endometrioses were also examined. Vascular endothelial cells were always positive for all the markers examined, and were used as positive controls. The frequencies of positivity for platelet-derived growth factor receptor-alpha and receptor-beta, and platelet-derived growth factor A-chain increased in accordance with higher cytologic atypia in the putative precursors: 71, 47, and 59% in the 17 non-atypical endometrioses, 84, 73, and 84% in the 19 atypical endometrioses, 0% each in the 10 non-atypical clear-cell adenofibromas, 100, 90, and 90% in the 10 atypical clear-cell adenofibromas, and 97, 97, and 100% in the 31 clear-cell adenocarcinomas, respectively. Positivity for platelet-derived growth factor B-chain increased in accordance with increased atypia in clear-cell adenofibroma: 0% in non-atypical clear-cell adenofibromas, 30% in atypical clear-cell adenofibromas, and 60% in coexisting carcinomas. However, in contrast, positivity for platelet-derived growth factor B-chain decreased in accordance with increased atypia in endometriosis coexisting with clear-cell adenocarcinomas: 35% in non-atypical endometrioses, 11% in atypical endometrioses, and 5% in coexisting carcinomas. Platelet-derived growth factor receptor-alpha and receptor-beta, and their ligands A-chain and B-chain were positive in 14, 29, 19, and 62% of the solitary endometrioses, respectively. These results indicate activation of the platelet-derived growth factor pathway in ovarian clear-cell adenocarcinomas and suggest biological differences between carcinomas that arise in association with clear-cell adenofibroma vs endometriosis.
Yamamoto
Sohei
S
Department of Basic Pathology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Tsuda
Hitoshi
H
Takano
Masashi
M
Kita
Tsunekazu
T
Kudoh
Kazuya
K
Furuya
Kenichi
K
Tamai
Seiichi
S
Matsubara
Osamu
O
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000232:Adenofibroma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D009378:Neoplasms, Multiple Primary; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*
D014408:Biomarkers, Tumor; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor