Basal-like
carcinomas have recently been identified in gene expression profiling studies as a subtype of invasive
breast cancer. These lesions are
estrogen receptor (ER)-negative,
progesterone receptor (PR)-negative, and HER2-negative (triple negative), and typically express basal cytokeratins,
epidermal growth factor receptor (EGFR), and/or c-kit. As poorly differentiated invasive
ductal carcinomas, they presumably have a
ductal carcinoma in situ (
DCIS) precursor with similar cytologic and immunophenotypic features. However, the frequency and even the existence of a
DCIS lesion with an immunophenotype analogous to that of invasive basal-like
carcinomas have not been previously evaluated. We studied 66 cases of high nuclear grade
DCIS using
antibodies to ER, PR, HER2, three basal cytokeratins, EGFR, and c-kit to determine the frequency of the triple negative phenotype, and to determine the relationship between the triple negative phenotype and expression of basal cytokeratins and other
biomarkers characteristically expressed by invasive basal-like
carcinomas. Four cases (6%) exhibited the triple negative phenotype; the remaining cases showed other combinations of ER, PR, and HER2 expression (nontriple negative). Basal cytokeratins, EGFR, or both were expressed by all four triple negative lesions, but by only 21 of 51 (42%) nontriple negative cases (P = 0.04). We conclude that a small proportion of high-grade
ductal carcinomas in situ exhibit an ER-negative/PR-negative/HER2-negative (triple negative) phenotype, and these lesions more commonly show expression of basal cytokeratins and/or EGFR than nontriple negative high-grade
DCIS. Given that invasive breast
cancers typically share immunophenotypic features with the
ductal carcinoma in situ from which they arise, our findings raise the possibility that the triple-negative, basal
cytokeratin and/or EGFR-positive
DCIS lesions we identified represent a precursor lesion to invasive basal-like
carcinomas.