Expression of platelet-derived growth factors and their receptors in ovarian clear-cell carcinoma and its putative precursors.

Abstract

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.

• Authors: Sohei Yamamoto, Hitoshi Tsuda, Masashi Takano, Tsunekazu Kita, Kazuya Kudoh, Kenichi Furuya, Seiichi Tamai, Osamu Matsubara
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 21 Issue 2 Pg. 115-24 (Feb 2008) ISSN: 0893-3952 [Print] United States
• PMID: 18084257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Platelet-Derived Growth Factor
• Receptors, Platelet-Derived Growth Factor

Topics

• Adenocarcinoma, Clear Cell (metabolism, pathology, surgery)
• Adenofibroma (metabolism, pathology, surgery)
• Biomarkers, Tumor (metabolism)
• Endometriosis (metabolism, pathology, surgery)
• Endothelium, Vascular (metabolism, pathology)
• Female
• Humans
• Immunoenzyme Techniques
• Neoplasms, Multiple Primary
• Ovarian Neoplasms (metabolism, pathology, surgery)
• Platelet-Derived Growth Factor (metabolism)
• Precancerous Conditions (metabolism, pathology)
• Receptors, Platelet-Derived Growth Factor (metabolism)