EVALUATION OF NEWER PROGNOSTIC MARKERS FOR ADULT SOFT-TISSUE SARCOMAS

Purpose: In addition to tumor size, grade, location, presence of metas tases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR -1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expr ession to clinical outcome in adults with STS. Patients and Methods: S nap-frozen STS specimens from 65 patients were analyzed and compared w ith clinical outcomes. Immunohistochemistry was performed for the Ki-6 7 antigen and P-gp. DNA content was determined using the Feulgen react ion and quantitated using image analysis. MDR-1 mRNA expression was de termined using a reverse-transcriptase polymerase chain reaction (RT-P CR)-based assay. Results: P-glycoprotein expression was found by immun ohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .0 7) and disease-free survival rates (32% v 18%, P = .039) higher in hig h-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 5 1% of cases and no patient with high levels of MDR-1 mRNA expression w as a long-term survivor, Patients with diploid tumors had significantl y better survival than those with nondiploid tumors (51% v 31%, P = .0 3). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04), On multivariate analysis, American Joint Committ ee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining wer e significant prognostic factors for 5-year overall and disease-free s urvival. Conclusion: P-gp expression, high-level Ki-67 expression, and nondiploid DNA content ore independent prognostic indicators that cor relate with poor outcomes in STS patients, However, MDR-I mRNA was not found to be predictive of survival, These newer markers are useful ad ditions to AJCC staging for prognostication for patients with STS. Suc h markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy. (C) 1997 by American Society o f Clinical Oncology.