Clinicopathologic analysis of k-ras, p53, and ERBB-2 gene alterations in pulmonary adenocarcinoma

D. W. Visscher, S. Yadrandji, P. Tabaczka, M. Kraut, F. H. Sarkar

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We compared PCR-SSCP detected mutations of k-ras (codon 12) and p53 (exons 5-8) to ERBB-2 immunostaining and clinicopathologic features in 31 pulmonary adenocarcinomas. There were nine tumors (29%) with mutations of ras, 13 tumors (42%) with mutations of p53, and three tumors (10%) with mutations of both. Neither k-ras nor p53 mutation alone was significantly correlated with stage, grade, or survival. However, tumors with k-ras mutation were more frequently associated with an invasive growth pattern, defined as >30% tumor volume composed of infiltrative nests of cells within desmoplastic, scar-like stroma [<30% volume invasive-1/13 (8%) with k-ras mutation vs. >30% volume invasive-8/18 (44%) with k-ras mutation, p = 0.02]. Accordingly, k-ras mutations were observed in only 1/9 (15%) predominantly bronchoalveolar or papillary tumors versus 6/22 (28%) acinar or scar carcinoma tumors. All three patients with combined k-ras/p53 mutation had advanced stage (III/IV) at presentation and died of the disease. In contrast to k-ras, staining for ERBB-2 was more frequently observed in tumors exhibiting <30% invasive growth pattern (12/13, 92%) than in tumors with >30% invasive growth pattern (10/18, 56%, p = 0.03). ERBB-2 immunoreactivity was more frequent in Stage I (14/15, 93%) versus Stage II-IV (8/16, 50%) cases, but it did not correlate with survival. There was a reciprocal relationship between k-ras mutation and ERBB-2 staining; only 4/9 (44%) k-ras mutated cases were ERBB-2 positive versus 18/22 (82%) cases without k-ras mutation (p = 0.005). In contrast, 8/13 cases with p53 mutation were ERBB-2 positive. We conclude that well-differentiated and less invasive papillary and bronchoalveolar tumors are more often ERBB-2 positive/k-ras negative (i.e. at codon 12), whereas less well differentiated acinar or scar carcinomas are more often ERBB-2 negative/k-ras mutated at codon 12. These findings imply that the divergent histogenesis of pulmonary adenocarcinoma may reflect specific differences in genetic pathology.

Original languageEnglish (US)
Pages (from-to)64-69
Number of pages6
JournalDiagnostic Molecular Pathology
Volume6
Issue number1
DOIs
StatePublished - Feb 1 1997

Keywords

  • ERBB-2
  • Pulmonary adenocarcinoma
  • k-ras mutations
  • p53 mutations

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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