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[221] Array Comparative Genomic Hybridization (aCGH) and Immunophenotype Analysis of a Series of 88 Ductal Carcinomas In Situ of the Breast

A Vincent-Salomon, N Gruel, C Lucchesi, V Raynal, G Pierron, B Sigal-Zafrani, P Freneaux, M Lae, RJ Salmon, A Fourquet, X Sastre-Garau, O Delattre. Institut Curie, Paris, France

Background: To analyse the immunophenotype and the genotype of a series of high grade (HG) and non high grade (NHG) ductal carcinomas in situ of the breast.
Design: The aCGH profile, TP53 sequence and immunophenotype (ER, PR, HER2, TP53, KRT5/6, KRT8/18 and EGFR) were determined in a series of 49 HG (including 23 microinvasive cases (MI)) and 39 NHG (including 12 MI cases) DCIS.
Results: Twelve recurrent (in at least 2 tumors) amplicons, located on chromosome 1, 8, 11, 17 and 20, were identified in 51 different tumors (19/51, 37% NHG; 32/51, 63% HG). The HER2 amplicon was the most recurrent (27/88 cases), in HG (22/27; 82%), ER/PR negatives (23/27; 85%) DCIS. Interestingly, 15/27 HER2 amplified cases presented rare other alterations on aCGH profile. CCND1 was amplified in 5/88 cases (3 NHG; 2HG and 4 non MI; 1 MI). The 8q24 MYC region was gained in 12/88 cases (4 NHG; 8 HG and 8 non MI and 4 MI). A TP53 mutation was present in 10/88 cases (2 NHG, 8 HG and 4 non MI, 6 MI cases). Thirty-four regions of gains on chromosome 1, 5p, 2p, 6p, 7p, 8, 11q, 12q, 14q, 16p, 17, 19p and 22 and nineteen regions of losses on chromosome 2p, 11q, 16q, 22, 20q were observed with a recurrence rate above 10% of the 88 cases. ER positive DCIS were characterized by gains of 1q, 8, 16p, 20q, CCND1 amplification and 16q losses and a higher number of gains and losses than ER negative HER2 amplified DCIS. 5/ 88 cases (6%) demonstrated a basal-like immunophenotype not associated with a recurrent aCGH profile.
Conclusions: Our results show that (1) DCIS present a low number of recurrent alterations (2) TP53 mutations, HER2, CCND1 and MYC activation occur in DCIS and are not involved in the invasion process (3) HER2 amplified DCIS are ER negative HG tumors, classified in two groups, one presenting rare other genomic alterations beside HER2 activation (4) ER positive DCIS present a higher number of gains and losses than ER negative HER2 amplified DCIS, suggesting that ER negative and ER positive DCIS follow different carcinogenesis processes (5) A group of DCIS presented a basal-like phenotype but are not, in this small series, associated with a specific genotype. Phenotypic/genotypic characterisation should improve DCIS classification and could, in a near future, be helpful to stratify patients therapy.
Category: Breast

Monday, March 26, 2007 9:00 AM

Platform Session: Section D, Monday Morning