Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas

Chih Yi Hsu, Robert Bristow, Seok Cha Moon, Brant G. Wang, Chung Liang Ho, Robert J. Kurman, Tian Li Wang, Ie Ming Shih

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Mitogen-activated protein kinase (MAPK) plays a pivotal role in signal transduction. Activation of MAPK is regulated by upstream kinases including KRAS and BRAF, which are frequently mutated in low-grade ovarian serous carcinoma. This study evaluates the expression of active MAPK in ovarian serous carcinomas, with response to treatment and survival. Experimental Design: Expression of active MAPK was assessed by immunohistochemistry in 207 cases of ovarian serous tumors. Immunoreactivity was correlated with tumor grade, mutational status of KRAS and BRAF, in vitro drug resistance, and clinical outcome. Result: There was a lower frequency of expression of active MAPK in high-grade ovarian serous carcinomas as compared with low-grade serous tumors, including border-line tumors and low-grade serous carcinoma (P < 0.001). Active MAPK was present in all of the 19 low-grade tumors with either KRAS or BRAF mutations as well as in 14 (41%) of 34 tumors with wild-type KRAS and BRAF in both low-and high-grade carcinomas. Expression of active MAPK alone served as a good survival indicator in the 2-year follow-up (P = 0.037) but not in the 5-year follow-up (P = 0.145). However, a combination of expression of active MAPK and in vitro sensitivity of paclitaxel significantly correlated with a better prognosis in 5-year survival rate (P = 0.048) in patients with advanced-stage high-grade serous carcinoma. Conclusions: Active MAPK is more frequently expressed to low-grade than in high-grade ovarian serous carcinoma. Active MAPK serves as a good prognostic marker in patients with high-grade serous carcinomas.

Original languageEnglish (US)
Pages (from-to)6432-6436
Number of pages5
JournalClinical Cancer Research
Volume10
Issue number19
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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