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HER-2 Is an Independent Prognostic Factor in Endometrial Cancer: Association With Outcome in a Large Cohort of Surgically Staged Patients

Carl Morrison, Vanna Zanagnolo, Nilsa Ramirez, David E. Cohn, Nicole Kelbick, Larry Copeland, Larry G. Maxwell, Jeffrey M. Fowler

From the Department of Pathology, Division of Gynecologic Oncology Center for Biostatistics, The Arthur James Cancer Hospital, and the Richard Solove Research Institute, The Ohio State University Medical School Columbus, OH; and the Division of Gynecologic Oncology, Walter Reed Army Medical Center, Washington, DC.

Address reprint requests to Carl Morrison, MD, DVM, Pathology Core Facility, 418-M SL 320 W 10th Ave, Columbus, OH 43210; e-mail: morrison4{at}medctr.osu.edu

Purpose To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data.

Patients and Methods A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging.

Results Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years).

Conclusion Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.

Supported by Grant No. BAA051 from the Department of Defense Health Systems/US Army Medical Research and Material Command Gynecologic Cancer Center for the Study of Racial Disparities of the Uniformed Services University of the Health Sciences.

Presented in part in abstract form at the 36th Annual Meeting of the Society of Gynecologic Oncologists, Miami, FL, March 19-22, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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