Correlation of alpha-feto-protein receptor expression to advancing stage and grade of non-small cell lung cancer

Background: Expression of alpha feto-protein (AFP) receptor isoforms may be an early phenotypic marker of the commitment of cells to apoptosis. Isoforms H.1 and H.4 are thought to regulate commitment and resistance of cells to programmed cell death (PCD) respectively. Their relationship to the progression of non-small cell lung cancer (NSCLC) has not bee previously evaluated. Design: Sections from 101 cases of NSCLC for which frozen tissue was available from the time of resection were immunostained with monoclonal antibodies to AFP receptor 167H.1 (1:50, Chemicon, Temecula, CA) and 167H.1 (1.50) using an enhanced sensitivity avidin-biotin peroxidase technique. Immunopositivity for the AFP receptor isoforms and H.4:H.1 ratio were correlated with cell type, stage and grade. Results: Expression of H.1 was similar for all stages. Frequency of H.1 expression decreased from Stage I (51%) to Stage II/IIIA (38%) tumors. Frequency of H.1 expression decreased from low-grade (59%) to high-grade (48%) tumors. H.4:H.1 increased from Stage I to Stage II for all adenocarcinomas (AC) (1.28 to 2.52), acinar AC (1.13 to 1.97), bronchioloalveolar AC (1.57 to 4.00) and squamous cell carcinomas (1.51 to 2.00). Conclusion: Loss of H.1 (commitment to PCD) expression occurs with advancing tumor stage and grade and may contribute to progression of NSCLC. Manipulation of H.1 expression may be a potential therapeutic approach to NSCLC.