Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients

Abstract

BACKGROUND: Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer. METHODS: In a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data. RESULTS: In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model. CONCLUSIONS: PMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.