Most Basal-like Breast Carcinomas Demonstrate the Same Rb-/p16+Immunophenotype as the HPV-related Poorly Differentiated Squamous Cell Carcinomas Which They Resemble Morphologically

Basal-like carcinomas (BLCs) of the breast share discriminatory morphologic features with poorly differentiated high-risk human papilloma virus (HPV)-related squamous cell carcinomas of the oropharynx, penis, and vulva. Because HPV E7 protein inactivates the retinoblastoma (Rb) protein, diffuse p16 expression is a surrogate marker for these high-risk HPV-related carcinomas. HPV E6 protein also inactivates p53, further compromising the G(1)-S cell cycle checkpoint. The Rb/p16/p53 immunohistochemical profile of BLC of the breast has not been well characterized. Tissue microarrays containing 71 invasive ductal carcinomas (IDCs) of the breast were immunolabeled for p 16, Rb, p53, and Ki-67. The cases included 4 distinct groups of IDCs having surrogate immunohistochemical profiles corresponding to categories defined by gene expression profiling (17 luminal A, 7 luminal B, 14 HER-2+, and 21 BLC), along with 12 unclassifiable triple negative carcinomas (UTNCs). Twenty-five of the 71 IDC were Rb negative/p16 diffuse positive (Rb-/p16+). These included 15 of 21 BLC and 9 of 12 UTNC, but only I of 14 HER-2 positive cases and none of the 17 luminal A or 7 luminal B cases (P < 0.0 1, BLC or UTNC vs. others). Six of the Rb-/p16+ IDC also had a significant ductal carcinoma in Situ component. The ductal carcinoma in situ in 4 of these 6 cases showed the same Rb-/p16+ phenotype as the associated IDC. BLC and UTNC had the highest Ki-67 indices of the 5 groups, even when matched for grade. The Rb-/p16+ phenotype and the Rb-/p16 +/p53 overexpressing phenotype correlated with increased proliferation within the BLC group. In Conclusion, BLC and UTNC, but not HER-2, luminal A, or luminal B carcinomas, frequently demonstrate an Rb-/p16+ phenotype, similar to the HPV-related squamous cell carcinomas that BLC resemble morphologically. This subset may represent a more homogenous group than BLC as defined currently.