Abstract P3-07-01: Clonal Relatedness between Lobular Carcinoma In Situ and Synchronous Malignant Lesions: Analysis of Fresh Frozen Tissue Using SNP Array

Abstract

INTRODUCTION: Lobular carcinoma in situ (LCIS) confers one of the greatest risks for subsequent development of invasive breast carcinoma yet historical data suggests that LCIS is not a precursor to invasive disease. Emerging evidence of shared molecular alterations between LCIS and co-existing invasive lesions in a small number of archival samples have reopened the debate regarding the true significance of LCIS and its malignant potential. METHODS: We investigated clonality between LCIS and adjacent malignant lesions in 26 patients using fresh frozen samples harvested from mastectomy specimens. Laser Capture Microdissection was used to isolate pure cell populations and DNA was subject to Affymetrix SNP 6.0 array. Data were converted for copy number analysis and the closeness of identified paired copy number changes was measured to determine the probability of clonality. RESULTS: After excluding cases with low DNA yield/quality and noise signals, 14 LCIS with seven patient matched invasive lobular carcinomas (ILC), 6 matched ductal carcinoma in situ (DCIS) and 3 matched invasive ductal carcinomas with lobular features (IDCLF) were considered adequate for statistical comparison. The immunohistochemical profile of invasive cancer showed: 10 cases ER+/PR+/Her-2(-), 2 cases ER-/PR-/Her-2(+), 1 ER-/PR-/Her2(-) and 1 case non-available for staining (microinvasive carcinoma). The results suggest that the tumor pairs are more likely to be of clonal than independent origin between LCIS and DCIS in 4/6 samples (66.6%), between LCIS and low-grade IDCLF in 3/3 (100%) samples and between LCIS and classic ILC in 5/7 (71.4%) samples. Independent LCIS/DCIS samples were seen in association with Her2+ cancers. In LCIS/DCIS samples favoring a clonal origin the DCIS were low-grade cribriform type associated with ER+ cancers. CONCLUSION: Clonal relatedness was detected in the majority of LCIS and adjacent malignancies, including cases of low-grade DCIS and IDCLF. These results support a true precursor role for LCIS and provide additional evidence to the concept of a low-grade malignancy pathway as opposed to the classic lobular versus ductal dichotomy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-07-01.