B7H1 Expression and Association with Clinical Response to Sunitinib Therapy in Metastatic Renal Cell Carcinoma Patients
Jenny J Kim, Enrico Munari, Nilda Gonzalez-Roibon, Haiying Xu, Housam Haddad, Robert Anders, Sehbal Arslankoz, Hang Wang, Zhe Zhang, Sarah Rapp, Laura Wood, George J Netto, Charles Drake, Gary Rosner, Brian I Rini. Johns Hopkins Pathology, Baltimore, MD; Johns Hopkins Hospital, Baltimore, MD; Hacettepe University School of Medicine, Ankara, Turkey; Johns Hopkins University, Baltimore, MD
Background: B7H1 is involved in apoptosis of activated T cells and plays an important role in the suppression of immune response. Preliminary data support that B7H1 expression is associated with objective response (OR) to anti PD-1 antibody treatment in multiple tumors. The aim of this study was to retrospectively evaluate a possible association between B7H1 expression and clinical response to sunitinib therapy in metastatic clear cell renal cell carcinoma (mRCC).
Design: Immunohistochemistry (IHC) staining for B7H1 was performed on pretreatment formalin fixed paraffin embedded (FFPE) tissue sections from patients with mRCC receiving sunitinib therapy (50mg 4/2) with available clinical data according to our institution protocol. Two independent pathologists who were blinded to outcomes scored IHC; a third pathologist intervened if a discrepancy between the first 2 occurred. Positivity was defined if >5% of cells showed membranous staining. Association of B7H1 expression with OR was assessed using Fisher's exact test. Estimation and comparison of progression free survivals (PFS) were conducted using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using logistic regression and Cox regression.
Results: We identified 20 cases of which 18 had available FFPE samples for IHC analysis. 89% of patients were therapy naïve and 78% were male. Median age was 55 (range 35-79); 72% showed ECOG PS of 0; 94% had prior nephrectomy; 50% were intermediate risk category according to Heng criteria and the rest were poor risk. 55.6% were positive for B7H1 expression. OR was seen in 30% of B7H1 positive patients and 50% of B7H1 negative patients (p=0.63). Median PFS were 19.3 and 6.2 mos for B7H1 negative and positive groups, respectively (p=0.56). After adjusting for Heng risk classification, B7H1 expression was neither associated with OR (odds ratio=0.54, 95% CI=0.07-4.23, p=0.56) nor PFS (hazard ratio=1.06, 95% CI=0.34-3.34, p=0.92) in multivariate models.
Conclusions: In this study, B7H1 expression was not associated with clinical outcome to sunitinib therapy in metastatic RCC patients.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 133, Wednesday Morning