Cytokeratin 5/6, c-Met expressions, and PTEN loss prognostic indicators in triple-negative breast cancer.

Abstract

In subgroups of breast cancer, the shortest disease-free and overall survival was observed in basaloid and human epidermal growth factor receptor-2 groups. CK5/6 expression is a marker used in diagnosing breast cancers in basaloid group and is associated with a poor prognosis. Similarly, loss of tumor suppressor gene PTEN and a high expression of c-Met has been associated with poor prognosis in breast cancer and many other cancers. In this study, we aimed to determine the effect of CK5/6 and c-Met expressions, and PTEN loss on the disease prognosis in triple-negative breast cancer patients. Ninety-seven patients pathologically diagnosed with triple-negative breast cancer were enrolled. The clinical and pathological characteristics of the patients were recorded. c-Met, PTEN, and CK5/6 expressions were evaluated with immunohistochemical methods from paraffin blocks. The median age of patients was 47 years. CK5/6 positivity was 50.5 %, PTEN loss was 44.3 %, and high c-Met expression was detected in 53.6 %. In multivariate analysis, predictors of the recurrence were loss of PTEN (HR = 2.99; P = 0.004), high c-Met expression (HR = 2.05; P = 0.06), CK5/6 expression (HR = 2.99; P = 0.02), increase in the number of metastatic lymph nodes (HR = 1.11; P = 0.001), and an increase in tumor size (HR = 1.226; P = 0.01). Also, PTEN loss (HR = 2.43; P = 0.05), CK5/6 expression (HR = 3.74; P = 0.01), and N2-3 tumors compared to negatives (HR = 3.63; P = 0.01) were associated with death. PTEN loss correlated with those of lymphovascular invasion. There was a correlation between CK5/6 expression and the number of metastatic lymph nodes. Also, a correlation was found among cancers with highly expressed levels of c-Met, T1-2 tumors, and high-grade tumors. The classical markers, lymph node involvement and tumor size, were found to be of prognostic value; however, high c-Met and CK5/6 expressions, and PTEN loss were found to increase risk of recurrence and death in patients with triple-negative breast cancer.

• Authors: Mevlude Inanc, Metin Ozkan, Halit Karaca, Veli Berk, Oktay Bozkurt, Ayse Ocak Duran, Ersin Ozaslan, Hulya Akgun, Fatos Tekelioglu, Ferhan Elmali
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 31 Issue 1 Pg. 801 (Jan 2014) ISSN: 1559-131X [Electronic] United States
• PMID: 24326984 (Publication Type: Journal Article)

Chemical References

• KRT5 protein, human
• KRT6A protein, human
• Keratin-5
• Keratin-6
• MET protein, human
• Proto-Oncogene Proteins c-met
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Adult
• Aged
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Keratin-5 (metabolism)
• Keratin-6 (metabolism)
• Lymphatic Metastasis
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• PTEN Phosphohydrolase (metabolism)
• Prognosis
• Proto-Oncogene Proteins c-met (metabolism)
• Recurrence
• Risk
• Triple Negative Breast Neoplasms (diagnosis, metabolism)