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

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 (Po0.05). HER2/neu, p53, and vascular endothelial growth factor expression was associated with significantly shorter survival (log rank, Po0.05). 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 (Po0.05). HER2/neu positivity showed a significant correlation with shorter survival (log rank, Po0.05) 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.

Current Concepts in Bronchioloalveolar Carcinoma Biology

“…p53 was overexpressed in only 8% of AAH and 4% to 16% of pure BAC tumors compared with 35% to 53% of adenocarcinomas (15,19). Tumors with mixed BAC histology had intermediate levels of expression.…”

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

“…Surprisingly, overexpression is associated with lower stage and grade of tumor [182]. Interestingly, there is an association of HER2/neu overexpression with NSCLC resistance to chemotherapy [183][184][185][186][187][188][189][190][191], which may account for the fact that HER2/neu overexpression is associated with a poor prognosis [35,[160][161][162][163][164][165][166][167][168][169][170][171][172][173] despite the association of HER2/neu overexpression with lower stage and grade. There is evidence for cooperativity and co-expression of HER1/EGFR [192], potentially associated with poorer prognosis [161,169,193], and there is data to support overexpression of HER2/neu as a mechanism for resistance to antibody inhibition of HER1/EGFR [194].…”

OCIA domain containing 2 is highly expressed in adenocarcinoma mixed subtype with bronchioloalveolar carcinoma component and is associated with better prognosis

“…(9)(10)(11)(12) Many molecular profiling studies by cDNA microarray have been carried out to identify the molecular targets in cancer cell for diagnosis and treatment. (13)(14)(15) However, definitive marker genes for the progression of adenocarcinoma mixed subtype with BAC component have not been identified.…”