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 important mechanism of multidrug resistance (MDR) in cancer. Its role in chemotherapy resistance in soft tissue sarcoma is unclear.


METHODS
Tumor specimens prior to and following neoadjuvant chemotherapy from 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclonal antibodies (C494 and JSB-1) that recognize different epitopes of P-glycoprotein. Staining intensity was graded 0 = negative, 1 = equivocal, 2 = moderate, 3 = strong. Only cases with Grade 2 or 3 staining intensity with both antibodies were considered MDR positive. The resection specimens were evaluated 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 19 (66%) were MDR negative. Pathologic response to treatment was characterized as good in 6, moderate in 7, and poor in 16 patients. Of the MDR positive biopsies, 9 (90%) had poor response, compared with 7 (36%) in the MDR negative biopsy group (P = 0.0078). None of the cases with MDR positive biopsies had a good response, compared with 6 cases in which biopsies were MDR negative (32%) (P = 0.057). Only one MDR negative case became MDR positive posttreatment.


CONCLUSIONS
Expression of MDR phenotype is found in approximately one-third of high grade soft tissue sarcomas. These preliminary data show a significant correlation between MDR phenotype and poor pathologic response to chemotherapy, and suggest that MDR induction by chemotherapy in soft tissue sarcoma is an uncommon event.
Jimenez
R E
RE
Department of Pathology, Harper Hospital, Wayne State University and the Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Zalupski
M M
MM
Frank
J J
JJ
Du
W
W
Ryan
J R
JR
Lucas
D R
DR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D002081:Buttocks; D018432:Drug Resistance, Multiple / Q000235:genetics*; D000939:Epitopes / Q000032:analysis; D005121:Extremities; D005260:Female; D006119:Groin; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012509:Sarcoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000939:Epitopes