In microdissected ductal carcinoma in situ, HER-2/neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology

BACKGROUND. HER-2/neu and p53 are two molecular markers that have been die focus of investigation in patients with invasive breast carcinoma. However, most of the published data have relied on immunohistochemical detection of the proteins as a surrogate marker of the underlying genetic alterations, a detection method that often gives variable results due to technical facto rs. In addition, there are limited data documenting HER-2/neu amplification and p53 mutations in the various histologic subtypes of ductal carcinoma i n situ (DCIS). The authors evaluated a series of microdissected, pure DCIS lesions comprising a spectrum of morphologic subtypes (comedo, micropapilla ry, papillary, cribriform, and solid) and their corresponding normal breast tissue for generic aberrations in HER-2/neu and p53. METHODS. HER-2/neu amplification was determined by differential polymerase chain reaction, and p53 mutations were identified by single-strand conforma tion polymorphism analysis. RESULTS. HER-2/neu amplification was identified in 12 of 30 DCIS samples (4 0%), and p53 mutations were identified in 6 of 30 DCIS samples (20%). The g enetic alterations were not present in any of the normal breast tissue samp les. HER-2/neu amplification occurred predominantly in the comedo subtype ( 69% vs. 18% of the noncomedo subtype; P = 0.008) and in lesions of high nuc lear grade (63% vs. 14% of low grade; P = 0.01). There was no difference in the frequency of p53 mutations among the subtypes or between low grade and high grade lesions. No correlation between the presence of the two genetic alterations was observed. CONCLUSIONS, The presence of HER-2/neu amplification, but not p53 mutations , correlates with histologic subtype and nuclear grade. The relatively freq uent occurrence of HER-2/neu amplification and p53 mutations in DCIS tissue and their absence in normal breast tissue suggest that these genetic aberr ations are important early in breast duct carcinogenesis. Cancer 2000;89:21 53-60. (C) 2000 American Cancer Society.