Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB-2, and cathepsin D protein

J Surg Oncol. 1997 May;65(1):22-7. doi: 10.1002/(sici)1096-9098(199705)65:1<22::aid-jso5>3.0.co;2-q.

Abstract

Background: In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer.

Objectives: The clinical utility of these molecular markers to predict recurrence was evaluated.

Methods: Archival pathology tissues of 100 breast cancer patients were analyzed by immunohistochemical assay. Molecular biologic data were merged with clinicopathologic variables.

Results: Thirty-two patients (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72 months). Investigational factor expression had statistical correlation for recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%, three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis, lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of nm23 protein expression were significant variables to determine recurrence; in multivariate analysis, node status and tumor size emerged as the most significant variables for recurrence.

Conclusions: Coexpression of the studied investigational variables functioned as significant prognostic correlates for recurrence. These findings suggest that the studied investigational prognostic factors possess the ability to discriminate a highly aggressive phenotype in breast cancer.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cathepsin D / genetics
  • Cathepsin D / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Monomeric GTP-Binding Proteins*
  • Multivariate Analysis
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Recurrence, Local / metabolism
  • Nucleoside-Diphosphate Kinase*
  • Phenotype
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • NM23 Nucleoside Diphosphate Kinases
  • Receptors, Estrogen
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Cathepsin D
  • Monomeric GTP-Binding Proteins