Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome

Abstract

While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. In a previous study of 78 breast carcinoma specimens, we noted an association between poor clinical outcome and the expression of cytokeratin 17 and/or cytokeratin 5 mRNAs. Here we describe the results of immunohistochemistry studies using monoclonal antibodies against these markers to analyze more than 600 paraffin-embedded breast tumors in tissue microarrays. We found that expression of cytokeratin 17 and/or cytokeratin 5/6 in tumor cells was associated with a poor clinical outcome. Moreover, multivariate analysis showed that in node-negative breast carcinoma, expression of these cytokeratins was a prognostic factor independent of tumor size and tumor grade.

Figure 1.

A: Normal mammary gland simultaneously stained with CAM5.2 monoclonal antibody [specific for keratins 8 and 18] (blue), and monoclonal anti-cytokeratin 17 (brown). Note that the CAM5.2 antibody specifically stains the lumenal epithelial cells, while the anti-cytokeratin 17 antibody specifically stains the basal epithelial cells of the normal mammary duct. B: Whole paraffin section of breast carcinoma stained with CAM5.2 monoclonal antibody (blue), and monoclonal anti-cytokeratin 17 (brown). Note the focal staining pattern for cytokeratin 17.

Figure 2.

A: Kaplan-Meier survival curve showing poor outcome in cytokeratin 17- and/or 5/6-positive tumors (P = 0.012). Clinical follow-up was available for 505 patients (mean, 65.9 months). A: No expression of CK17 or cytokeratin 5/6 in tumor cells. B: Expression of CK17 and/or cytokeratin 5/6 in tumor cells. B: The effect of cytokeratin 17 and/or cytokeratin 5/6 expression in 245 patients with negative lymph nodes (P = 0.006). The lymph node status was known in 474 patients. Patients expressing basal keratin (B) in this group have worse outcome than in patients without expression of these markers (A). Multivariate analysis showed that this effect was independent of tumor size, tumor grade, or Her2neu, ER, or GATA-3 expression.