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Correlation of abnormal RB, p16ink4a, and p53 expression with 3p loss of heterozygosity, other genetic abnormalities, and clinical features in 103 primary non-small cell lung cancers.

Publication ,  Journal Article
Geradts, J; Fong, KM; Zimmerman, PV; Maynard, R; Minna, JD
Published in: Clin Cancer Res
April 1999

This study was performed to determine the frequency of inactivation and clinical correlates in non-small cell lung cancer (NSCLC) of three known tumor suppressor genes [TSGs; RB, MTS1/CDKN2 (p16), and p53] and various regions of 3p loss of heterozygosity (LOH) as other major potential TSG sites. Paraffin sections from 103 resected NSCLCs were analyzed for expression of pRB, p16, and p53 by immunohistochemistry, whereas DNA from tumor and normal tissue were tested for LOH at 3p25-26, 3p21, and 3p14. Previously published LOH data for 5q, 11p, 17q, and 18q were also available. Loss of pRB or p16 expression and overexpression of p53 were considered abnormal. The immunohistochemical and LOH data were correlated with a variety of clinical parameters including stage, age, sex, smoking history, and survival. With respect to pRB, p16, and p53, the tumors could be grouped into four categories: normal for all three proteins (21%); abnormal for pRB or p16 and normal for p53 (30%); normal for pRB and p16 and abnormal for p53 (20%); and abnormal in both pathways (28%). Aberrant expression of pRB, p16, p53, and 3p LOH, either individually or in combination, was not associated with survival differences or any other clinical parameters, with the exception that pRB/pl6 abnormalities were more common in older patients (P = 0.0005). pRB and p16 expression showed a strong inverse correlation (P = 0.002), whereas there was no correlation between expression of pRB, p16, and p53. Abnormal expression of any of the three genes inversely correlated with K-ras codon 12 mutations (P = 0.004), but not with 3p LOH or LOH at other TSG loci. We conclude that resectable NSCLCs show distinct patterns of TSG inactivation, but that no clear clinical correlates exist either alone or in combination for pRB, p16, p53, and 3p abnormalities.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

April 1999

Volume

5

Issue

4

Start / End Page

791 / 800

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Survival Rate
  • Retinoblastoma Protein
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Loss of Heterozygosity
  • Immunohistochemistry
  • Humans
 

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

April 1999

Volume

5

Issue

4

Start / End Page

791 / 800

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Survival Rate
  • Retinoblastoma Protein
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Loss of Heterozygosity
  • Immunohistochemistry
  • Humans