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Published on: February 28, 2019

Analysis of K-ras, N-ras, H-ras, and p53 in lung neuroendocrine neoplasms

M E Couce1, D Bautista, J Costa

  • 1Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.

Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B
|September 4, 1999
PubMed

Insights

Point mutations in the p53 gene were infrequent in pulmonary neuroendocrine tumors and associated with higher-grade cancers. K-ras mutations were also linked to higher-grade carcinomas, while N-ras and H-ras mutations were absent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pulmonary neuroendocrine tumors (PNETs) encompass a spectrum of neoplasms.
  • Understanding the genetic alterations in PNETs is crucial for diagnosis and treatment.
  • The roles of p53, K-ras, H-ras, and N-ras genes in PNET development require further investigation.

Purpose of the Study:

  • To investigate point mutations in p53, K-ras, H-ras, and N-ras genes in various types of pulmonary neuroendocrine tumors.
  • To correlate the presence of these mutations with tumor grade and p53 protein expression.

Main Methods:

  • Screening of 11 typical carcinoid (TC), 4 atypical carcinoid (AC), 1 large cell neuroendocrine carcinoma (LCNEC), and 4 metastases samples.
  • Polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) and direct sequencing for gene mutation analysis.
  • Immunohistochemistry for p53 protein expression.

Main Results:

  • K-ras exon 1 mutations were found in two low-grade AC samples and one metastasis.
  • No mutations were detected in N-ras or H-ras genes.
  • p53 gene mutations (exons 5 and 8) were identified in one high-grade AC and one LCNEC.
  • p53 immunostaining was positive in three samples, but only one showed a corresponding genotypic mutation.
  • K-ras mutations were associated with higher-grade carcinomas.

Conclusions:

  • p53 gene mutations are infrequent in PNETs and correlate with higher tumor grades.
  • p53 mutation status does not consistently correlate with p53 protein expression.
  • K-ras mutations are associated with higher-grade pulmonary carcinomas.
  • N-ras and H-ras mutations are not prevalent in these PNETs.

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