Degree of Intratumoral EGFR and Cytokeratin 5/6 Expression Is Significantly Associated with Nodal and Distant Metastases in Patients with Basal-Like Triple-Negative Breast Carcinoma
LM Sutton, KH Molberg, VR Sarode, JS Han, J Sailors, Y Peng. UT Southwestern, Dallas, TX
Background: Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and Her2 negativity, is a group of aggressive tumors that can be further classified into two subtypes: basal-like, defined as cytokeratin (CK) 5/6 positivity and/or EGFR positivity by immunohistochemistry, and non-basal-like. Developing a novel treatment strategy to treat basal-like TN tumors is crucial for improving the prognosis of patients with these tumors.
Design: Clinical characteristics and tumor profiles were analyzed in 103 patients with TN tumors. Of these patients, 34 had distant metastatic disease, 34 had axillary nodal metastasis only, and 35 were nodal negative. The expression of basal cytokeratins (CK5/6, CK14, and CK17), EGFR, PTEN, and VEGF were compared between the distant metastatic, nodal metastatic, and nodal negative groups.
Results: There was no significant difference in the frequency of expression of these biomarkers between the 3 subgroups. However, among EGFR positive or CK5/6 positive cases (basal-like tumors), the combined nodal and distant metastatic group was found to have a significantly higher intratumoral expression of both CK5/6 (p<0.05) and EGFR (p<0.05) compared with the nodal negative group. There was no significant difference in the intratumoral expression of CK14, CK17, PTEN, and VEGF between subgroups of the basal-like tumors. In addition, the tumor size was significantly larger in the distant metastatic group as compared to the nodal metastatic or nodal negative groups (p<0.05, p<0.001 respectively), and the distant metastatic group had a significantly higher percentage of positive axillary lymph nodes in the axillary dissection as compared to the nodal metastatic group (p<0.05).
Conclusions: Our results indicate that basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of both EGFR and CK5/6 compared to those in the nodal negative group. Degree of intratumoral EGFR and CK5/6 expression may play a role in the development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer. In addition, larger tumor size and a higher percentage of positive axillary lymph nodes are more likely to be associated with distant metastases in TN breast cancer.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 37, Monday Morning