Please select Print from the file menu or right mouse click and choose print from the menu to print this page.

[128] Immunophenotypic Profile of the Basal-Like Subtype of Invasive Breast Carcinomas: Influence on Diagnosis and Therapy

LC Goldstein, SE Tirrell, TS Barry, SJ Kussick, PL Kandalaft, PM Kim, AM Gown. PhenoPath Laboratories, PLLC and IMPRIS, Seattle, WA

Background: Gene expression studies have identified a subset of invasive breast carcinomas with a basal-like gene expression pattern, corresponding to 15-20% of breast cancers. Patients with this breast cancer subset have a particularly poor clinical outcome. Studies using tissue microarrays have shown that these carcinomas demonstrate an immunohistochemical (IHC) profile characterized by negative expression of estrogen receptor (ER), progesterone receptor (PR) and HER2, and positive expression of cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), and c-KIT in a subset of cases. We undertook a study to expand this IHC profile on biopsy and resection specimens of invasive breast carcinomas and metastases from tumors of unknown origin in order to identify their relationship with the basal-like phenotype.
Design: A series of 102 breast carcinomas identified as negative for ER, PR, and HER2 were assessed by IHC for expression of CK5/6, EGFR, p53, p63, c-kit, mammaglobin, GCDFP-15, and MOC-31. Specimens were biopsies and resections as well as metastases. Immunostaining was performed using commercially available antibodies, and scoring was based on percentage of positive staining using conventional criteria. Additionally, a subset of tumors were tested for EGFR gene amplification by fluorescence in situ hybridization (FISH).
Results: All of the breast carcinomas were negative for ER, PR, and HER2. The IHC profile showed positivity rates of 76% for CK5/6, 66% for EGFR, 62.1% for c-kit, 53.5% for p53, and 49% for p63. Fewer cases were positive for GCDFP-15 (27.8%) and mammaglobin (18.9%) but 91.4% cases were positive for MOC-31. 1/27 carcinomas demonstrated amplification for EGFR by FISH.
Conclusions: This study expands on previously published reports showing that the basal-like subtype of infiltrating breast cancers has an immunophenotype with high positivity rates for CK5/6, EGFR, c-kit, p53, p63, and MOC-31. Clinicopathologic correlation is important in interpreting IHC markers in the context of tumors of unknown origin in that this basal subtype could be confused with carcinomas of squamous origin (positive for CK5/6, p63). The adenocarcinoma marker MOC-31 may be useful in this differential diagnosis. These tumors, positive for EGFR by IHC, may be targets of therapies such as gefitinib, but only 1/27 tumors showed gene amplification for EGFR by FISH.
Category: Breast

Monday, March 26, 2007 8:45 AM

Platform Session: Section D, Monday Morning