Research article

Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers

Chang H Song^1†, So Y Park^2†, Keun-Yong Eom¹, Jee H Kim³, Sung-Won Kim³, Jae S Kim¹ and In A Kim^1,3*

• * Corresponding author: In A Kim inah228@snu.ac.kr

• † Equal contributors

Author Affiliations

¹ Department of Radiation Oncology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Kyeongi-do, 463-707, Korea

² Department of Pathology, Seoul National University College of Medicine, Seongnam-si, Kyeongi-do, 463-707, Korea

³ Breast Care Center, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Kyeongi-do, 463-707, Korea

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Breast Cancer Research 2010, 12:R20 doi:10.1186/bcr2557

Published: 12 March 2010

Abstract

Introduction

Evaluating the expression of signaling molecule proteins from the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3-kinase (PI3K) pathway in invasive breast cancers may identify prognostic marker(s) associated with early relapse.

Methods

Immunohistochemical analyses of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), PI3K-p110α, phospho-AKT, phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer. Statistically significant relations between protein expression, clinicopathologic factors, and relapse-free survival (RFS) were analyzed.

Results

Expression of HSP90 was associated with 5-year RFS, as well as T stage, N stage, histologic grade, estrogen receptor (ER) expression, human epidermal growth factor receptor 2 (HER2) expression, and the Ki-67 proliferation index. On multivariate analysis, coexpression of HSP90 and PI3K-p110α or expression of HSP90 along with PTEN loss demonstrated significantly worse RFS. In subgroup analyses, both exhibited strong prognostic significance in HER2-positive cases, but not in HER2-negative cases.

Conclusions

The coexpression of HSP90 with PI3K-p110α or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers.