DE-NOVO EXPRESSION OF P-GLYCOPROTEIN ASSOCIATED WITH POOR-PROGNOSIS IN HIGH-GRADE NON-HODGKINS-LYMPHOMA

Chemotherapy has proven to be effective in the management of high grad e non-Hodgkin's lymphoma (NHL). However drug resistance remains a majo r clinical obstacle to effective disease control. One such well docume nted system involves multidrug resistance (MDR), characterized by the overexpression of a 170 kDa membrane protein termed P-glycoprotein (Pg p). Analysis of P-glycoprotein was done on lymph node biopsies obtaine d from 109 patients with high grade NHL. Patients were followed up for time periods ranging from 7 to 26 months after chemotherapy or until recurrent/residual disease was diagnosed. Analysis of Pgp in tissue sa mples was carried out by immunocytochemistry and Western blot. Of the 109 patients, 36 had either residual or recurrent disease. All these p atients had a second lymph node biopsy done which was also analyzed fo r Pgp. P-glycoprotein was detected by immunocytochemistry in only 5 of the 73 patients who remained disease-free, while it was expressed in 26 of the 36 patients with residual/recurrent disease. All the 36 tiss ue samples of the latter group and 42 of the 73 biopsies of the diseas e-free group were re-analyzed by Western blot. Only one of the 42 samp les from the disease-free group showed a positive Western blot reactio n while 30 of the 36 samples from patients with recurrent/residual dis ease gave a positive reaction. Thirty-four of the 36 repeat biopsy sam ples from patients with recurrent/residual disease were positive for P gp. Correlation analysis, thus showed significant relationship between prognosis and detection of Pgp by immunocytochemistry (r=0.85, p<0.00 1) and Western blot (r=0.90, p<0.001). Moreover, the odds ratio of a t umor positive for Pgp not responding to chemotherapy was 35.36 (CI 11. 03, 113.37). Thus evaluation for Pgp may prove to be a useful prognost ic marker for high grade NHL, and may also prove useful in designing o r altering chemotherapy protocols in such patients.