Prognostic significance of HER2/neu, p53, and vascular endothelial growth factor expression in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung

Mod Pathol. 2004 Oct;17(10):1235-42. doi: 10.1038/modpathol.3800171.

Abstract

In this study, we investigated the prognostic value of HER2/neu, p53, and vascular endothelial growth factor in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. We studied 100 patients and consisted of 50 cases with conventional adenocarcinoma and 50 cases with bronchioloalveolar carcinoma (32 nonmucinous and 18 mucinous subtypes). Representative sections were immunostained for HER2/neu, p53, and vascular endothelial growth factor. Positivity was scored quantitatively by three observers and correlated with multiple prognostic parameters including survival. In the conventional adenocarcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 19/50 (38%), 32/50 (64%), 33/50 (66%), respectively. In this group, p53 showed a significant correlation with recurrence while vascular endothelial growth factor correlated with angiolymphatic invasion (P < 0.05). HER2/neu, p53, and vascular endothelial growth factor expression was associated with significantly shorter survival (log rank, P < 0.05). Patient whose tumors coexpressed both p53 and HER2/neu had the worst outcome. In the bronchioloalveolar carcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 9/50 (18%), 3/50 (6%) and 12/50 (24%), respectively which was significantly less than in conventional adenocarcinoma (P < 0.05). HER2/neu positivity showed a significant correlation with shorter survival (log rank, P < 0.05) in nonmucinous type. In conclusion, vascular endothelial growth factor was associated with angiolymphatic invasion and poor prognosis in conventional adenocarcinoma. Also, in conventional adenocarcinoma, p53, and HER2/neu expression appeared to be poor prognostic markers, while in bronchioloalveolar carcinoma, only HER2/neu was associated with a poorer prognosis. This immunostaining pattern suggests that conventional adenocarcinoma has different molecular abnormalities than bronchioloalveolar carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / biosynthesis
  • Survival Analysis
  • Tumor Suppressor Protein p53 / biosynthesis
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Receptor, ErbB-2