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.

Immunohistochemical analyses of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), PI3K−p110alpha, 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 relationships between protein expression, clinicopathologic factors, and relapse−free survival (RFS) were analyzed.

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, co−expression of HSP90 and PI3K−p110alpha 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.

The co−expression of HSP90 with PI3K−p110alpha or expression of HSP90 along with PTEN loss have potential as molecular prognostic markers to predict early relapse in patients with invasive breast cancers.

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