Oncogenic potential of c-erbB-2 and its association with c-K-ras in premalignant and malignant lesions of the human uterine endometrium

Tumour Biol. 2001 Sep-Oct;22(5):299-309. doi: 10.1159/000050631.

Abstract

The aim of this study was to detect activated c-K-ras by gene point mutation and to find c-erbB-2 gene amplification with p185 expression in association with the c-K-ras gene product p21 in the human endometrium. Specimens obtained from 25 normal, 31 hyperplastic and 72 malignant samples of the human endometrium were examined for point mutation in codons 12, 13 and 61 of the c-K-ras by direct sequencing and c-erbB-2 gene amplification with p185 and p21 expression by differential polymerase chain reaction (DPCR) and immunohistochemistry. Neither the normal endometrium nor endometrial hyperplasias were found to have mutations in the c-K-ras gene, although a double mutation of codons 12 and 13 as a single-point mutation was observed in one case of endometrioid carcinoma (2.8%). In each of two other cases of endometrioid carcinoma (2/72), two single-point mutations of codon 13 (5.6%) were shown. Using DPCR, we found c-erbB-2 to be amplified in 15 premalignant (48%) and 45 malignant (63%) samples. We noticed that nonamplification of the c-erbB-2 gene was associated with the absence of immunoreactivity. Our data indicate that, while c-erbB-2 plays a role in the early development of endometrioid carcinomas, c-K-ras gene activation by point mutation does not.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • Codon
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology
  • Endometrium / pathology*
  • Female
  • Follow-Up Studies
  • Gene Amplification
  • Genes, erbB-2*
  • Genes, ras*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / mortality
  • Precancerous Conditions / pathology*
  • Proto-Oncogene Proteins p21(ras) / analysis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics*
  • Reference Values
  • Survival Rate
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / mortality
  • Uterine Neoplasms / pathology*
  • Uterus / pathology*

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Codon
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Receptor, ErbB-2
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)