Histologic Predictors of Renal Cell Carcinoma Response to... : Journal of Immunotherapy (original) (raw)

Clinical Study

Histologic Predictors of Renal Cell Carcinoma Response to Interleukin-2-Based Therapy

Upton, Melissa P*; Parker, Robert A†; Youmans, Amanda‡; McDermott, David F‡; Atkins, Michael B‡

From the *Beth Israel Deaconess Medical Center, Department of Pathology; †Biometrics Center, and ‡Division of Hematology/Oncology, Harvard Medical School, Boston, Massachusetts.

Received for publication July 23, 2004; accepted March 31, 2005.

Supported by a grant from the Kidney Cancer Association, Evanston, IL.

M.P.U. is currently at the Anatomic Pathology Division, Department of Pathology, University of Washington Medical Center, Seattle, WA. R.A.P. is currently at the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA.

Reprints: Michael B. Atkins, MD, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215 (e-mail: [email protected]).

Abstract

The authors examined pathology from patients with renal cancer (RCC) treated with IL-2 to determine response rates for clear cell and variant RCC and to identify histologic features that predict response. Pathology specimens were reviewed by a single pathologist who was blinded to both the prior pathology interpretation and the therapeutic response. Findings were correlated with response to IL-2 therapy. Evaluable pathology specimens were obtained from 231 patients. Of 163 primary RCCs, the response rate was 21% (30/146) for patients with clear cell versus 6% (1/17) for patients with variant or indeterminate type RCC (P = 0.20). For clear cell carcinomas, response to IL-2 was associated with the presence of alveolar features and the absence of papillary and granular features. Patients with more than 50% alveolar features and no granular or papillary features had a 39% response rate (14/36). Patients with alveolar and granular features representing less than 50% of the specimen and no papillary features had a 19% response rate (15/77). The response rate for the others was 3% (1/33). This model was then applied to an independent sample of 68 metastasis specimens. Response rates in the three prognostic groups and for patients with non-clear cell cancers were 25% (5/20), 9% (2/22), 0% (0/16), and 0% (0/10), respectively. Median survivals for all patients with clear cell tumors by risk group were 2.87, 1.36, and 0.87 years, respectively (P < 0.001). These data suggest that patients with non-clear cell RCC or with clear cell RCC with papillary, no alveolar, and/or more than 50% granular features respond poorly to IL-2 and should be considered for alternative treatments. Investigation of other tumor-related predictors of IL-2 responsiveness is warranted.