p16INK4a expression in basal-like breast carcinoma

Abstract

BLBC represents a distinctive group of invasive breast carcinomas with specific genotype and immunoprofile. BLBC is usually defined by gene expression profiling and is currently associated with poor outcome. BLBCs are estrogen receptor (ER) negative, progesterone receptor (PgR) negative, HER2 negative, and usually show a variable expression of basal cytokeratins (CKs), EGFR and CD117. p16(INK4a) is a tumor suppressor protein, encoded by the CDKN2A gene, which regulates cell cycle. The reported association of abnormalities in the p16/Rb pathway with increased risk of malignancy prompted us to determine the expression of p16(INK4a) in a group of BLBC; the results were compared with a group of high-grade invasive carcinoma (HG-IC) of breast. Tissue microarrays (TMA) were constructed in triplicate including 18 BLBC and 18 HG-IC. All BLBC cases were ER-/PgR-/HER2-. Seventeen (94%) BLBC were CK 5/6+/CK 14+; 14 (78%) BLCB showed EGFR expression and 13 (72%) were CD117 positive. BLBCs showed a strong positive reaction with p16(INK4a) antibody in 16 of 18 (89%) cases. Although the significance of p16(INK4a) expression in breast cancer is not fully understood, we have shown that p16(INK4a) is strongly expressed in breast cancers with basal-like phenotype. Since it is known that p16(INK4a) is associated with aggressive behavior in human carcinomas, these data suggest that p16(INK4a) play a role in the poor prognosis of BLBC.

Keywords: Breast cancer; HER2; basal cancer; estrogen receptor; immunohistochemistry; p16 INK4a; progesterone receptor.

Figure 1

Basal-like breast carcinomas demonstrating multiple mitotic figures. Hematoxylin-eosin (A), necrosis is present (B), strong p53 nuclear immunoreactivity (C) and high proliferative Ki67 index (D).

Figure 2

Basal-like breast carcinomas demonstrating CK5/6 immunoreactivity (A), CK14 immunoreactivity (B), TMA section showing p16 expression (C) and diffuse cytoplasmic/nuclear p16 expression (D). CK indicates cytokeratin; TMA, tissue microarray.