In microdissected ductal carcinoma in situ, HER-2/neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology Journal Article
| Authors: | Ho, G. H.; Calvano, J. E.; Bisogna, M.; Borgen, P. I.; Rosen, P. P.; Tan, L. K.; Van Zee, K. J. |
| Article Title: | In microdissected ductal carcinoma in situ, HER-2/neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology |
| Abstract: | BACKGROUND. HER-2/neu and p53 are two molecular markers that have been the 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 factors. In addition, there are limited data documenting HER-2/neu amplification and p53 mutations in the various histologic subtypes of ductal carcinoma in situ (DCIS). The authors evaluated a series of microdissected, pure DCIS lesions comprising a spectrum of morphologic subtypes (comedo, micropapillary, papillary, cribriform, and solid) and their corresponding normal breast tissue for genetic 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 conformation polymorphism analysis. RESULTS. HER-2/neu amplification was identified in 12 of 30 DCIS samples (40%), and p53 mutations were identified in 6 of 30 DCIS samples (20%). The genetic alterations were not present in any of the normal breast tissue samples. 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 nuclear 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 frequent occurrence of HER-2/neu amplification and p53 mutations in DCIS tissue and their absence in normal breast tissue suggest that these genetic aberrations are important early in breast duct carcinogenesis. (C) 2000 American Cancer Society. |
| Keywords: | clinical article; controlled study; human tissue; gene mutation; mutation; histopathology; cancer grading; polymerase chain reaction; phenotype; gene amplification; breast neoplasms; protein p53; cancer invasion; carcinoma in situ; dna, neoplasm; cell nucleus; genes, erbb-2; breast carcinogenesis; protein determination; intraductal carcinoma; genetic markers; genes, p53; ductal carcinoma in situ; dna polymorphism; carcinoma, ductal, breast; oncogene neu; p53 mutation; comedo; histologic subtypes; polymorphism, single-stranded conformational; nuclear grade; humans; human; female; priority journal; article; her-2/neu amplification |
| Journal Title: | Cancer |
| Volume: | 89 |
| Issue: | 11 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2000-12-01 |
| Start Page: | 2153 |
| End Page: | 2160 |
| Language: | English |
| DOI: | 10.1002/1097-0142(20001201)89:11<2153::aid-cncr2>3.0.co;2-o |
| PUBMED: | 11147584 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work