IMMUNOHISTOCHEMICAL STUDY OF P-GLYCOPROTEIN DISTRIBUTION IN LUNG-CANCER

Indirect immunoperoxidase was used to determine the reactivity of C219 (P-glycoCHEK C219TM, Centocor Diagnostics, Malvern, PA), a monoclonal antibody (Mab) with high affinity for an internal epitope of the P-gl ycoprotein encoded by the multidrug resistance (MDR1) gene, in 40 surg ically resected primary lung tumours. C219 reactivity was qualitativel y classified in seven small cell lung cancers (SCLC), 29 non small cel l lung cancers (NSCLC), and four carcinoid tumours. Ploidy was analyse d by means of static cytometry using a computer-assisted image process or following Feulgen staining of cytologic prints of 32/40 lung tumour s. Indirect immunoperoxidase reactivities of Mabs S-L 11.14 and MOC-1 were also studied to characterize the expression of cluster 1 lung can cer antigens and hence to determine among the NSCLC those which expres sed the neural cell adhesion molecule (NCAM). Eighteen (45%) lung tumo urs strongly expressed P-glycoprotein as an immunostaining of many isl ets of malignant cells or almost all malignant cells. In addition, 8/4 0 tumours (20%) showed a weak reactivity (few immunostained cells) and 14/40 (35%) no reactivity. There was no difference of reactivity when NSCLC were compared with SCLC. The expression of P-glycoprotein in NS CLC did not vary significantly when the stage of disease was considere d. Among the 29 NSCLC, 10 (36%) expressed S-L 11.14 and MOC-1. The NCA M positive NSCLC did not show any difference of P-glycoprotein express ion in comparison with NCAM negative ones. Finally, C219 immunoperoxid ase reactivity did not significantly differ according to the ploidy st atus, In conclusion, the internal epitope of the P-glycoprotein encode d by the MDR1 gene is frequently expressed by lung tumours of any hist ological type. This expression is not higher in Stage III and IV lung cancers in comparison with Stage I and II ones, or in NSCLC in compari son with SCLC either. Thus, the C219 related epitope seems to have a w eak implication in the lower chemosensitivity of both advanced stages and NSCLC.