Multidrug resistance phenotype in high grade soft tissue sarcoma - Correlation of P-glycoprotein immunohistochemistry with pathologic response to chemotherapy

BACKGROUND. P-glycoprotein-mediated drug efflux has been implicated as an i mportant mechanism of multidrug resistance (MBR) in cancer. Its role in che motherapy resistance in soft tissue sarcoma is unclear. METHODS. Tumor specimens prior to and following neoadjuvant chemotherapy fr om 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclon al antibodies (C494 and JSB-1) that recognize different epitopes of P-glyco protein. Staining intensity was graded 0 = negative, 1 = equivocal, 2 = mod erate, 3 = strong. Only cases with Grade 2 or 3 staining intensity with bot h antibodies were considered MDR positive. The resection specimens were eva luated for tumor necrosis postchemotherapy. Pathologic response was graded as good for <15%, moderate for 15-50%, or poor for >50% posttreatment tumor viability. RESULTS. Of the 29 pretreatment specimens, 10 (34%) were MDR positive and 1 9 (66%) were MDR negative. Pathologic response to treatment was characteriz ed as good in 6, moderate in 7, and poor in 16 patients. Of the MDR positiv e biopsies, 9 (90%) had poor response, compared with 7 (36%) in the MDR neg ative biopsy group (P = 0.0078). None of the cases with MDR positive biopsi es had a good response, compared with 6 cases in which biopsies were MDR ne gative (32%) (P = 0.057). Only one MDR negative case became MDR positive po sttreatment. CONCLUSIONS, Expression of MDR phenotype is found in approximately one-thir d of high grade soft tissue sarcomas. These preliminary data show a signifi cant correlation between MDR phenotype and poor pathologic response to chem otherapy, and suggest that MDR induction by chemotherapy in soft tissue sar coma is an uncommon event. (C) 1999 American Cancer Society.