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Down Regulation of High in Normal-1 (HIN-1) is a Frequent Event in Stage I Non-Small Cell Lung Cancer and Correlates with Poor Clinical Outcome

Departments of¹ Oncology and Neurosciences and ² Surgery, University G. D’Annunzio, Chieti, Italy, and ³ Department of Surgery, University of Pisa, Pisa, Italy

Purpose: The aim of this study was to evaluate the prevalence and the clinical significance of HIN-1 mRNA expression in early stage non-small cell lung carcinomas (NSCLCs).

Experimental Design: A series of 91 NSCLC patients with stage I neoplastic disease was studied. HIN-1 expression was investigated by quantitative real-time reverse transcription-PCR on tumor specimens and matching normal lung tissues. Variables were analyzed by ² test and Fisher’s exact tests. Survival was evaluated with the method of Kaplan-Meier. Multivariate analysis was performed with Cox’s proportional hazards model.

Results: Seventy one (78%) tumors showed a reduction of HIN-1 mRNA compared with the normal counterpart. The range of reduction varied greatly, from -2-fold to -3350-fold. Setting a cutoff at -46-fold (median value of HIN-1 mRNA reduction), 46 cases (51%) had a markedly reduced expression, and 45 cases (49%) showed a normal or slightly reduced expression. A statistically significant association between low HIN-1 mRNA levels and T status was observed (P = 0.036). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between HIN-1 expression and both overall survival (P = 0.0095) and disease-free survival (P = 0.0122). A multivariate analysis, performed by Cox’s proportional hazards regression model, confirmed that a low HIN-1 expression was the only significant factor to predict poor prognosis.

Conclusions: Our data indicate that HIN-1 expression, measured by real-time reverse transcription-PCR, is a possible prognostic factor in patients with stage I NSCLC. Additional studies are required to further validate this potential prognostic marker.

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