Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma

Daniel W Visscher, Rudolph Castellani, Susan Mary Wykes, Fazlul H. Sarkar, Mohamed E. Hussain

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative - 59% none positive, 29% one positive, 12% two or more positive, vs. node positive - 37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positve for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalBreast Cancer Research and Treatment
Volume28
Issue number3
DOIs
StatePublished - Jan 1993
Externally publishedYes

Fingerprint

erbB-1 Genes
p53 Genes
Disease Progression
Breast Neoplasms
Neoplasm Metastasis
Recurrence
Neoplasms
Staining and Labeling
Genes
Gene Expression
Chi-Square Distribution
Tumor Suppressor Genes
Oncogenes
Multivariate Analysis
Phenotype
Proteins

Keywords

  • breast carcinoma
  • EGF receptor
  • immunoperoxidase
  • oncogenes
  • tumor suppressor genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. / Visscher, Daniel W; Castellani, Rudolph; Wykes, Susan Mary; Sarkar, Fazlul H.; Hussain, Mohamed E.

In: Breast Cancer Research and Treatment, Vol. 28, No. 3, 01.1993, p. 261-266.

Research output: Contribution to journalArticle

Visscher, Daniel W ; Castellani, Rudolph ; Wykes, Susan Mary ; Sarkar, Fazlul H. ; Hussain, Mohamed E. / Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. In: Breast Cancer Research and Treatment. 1993 ; Vol. 28, No. 3. pp. 261-266.
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