title: Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy.
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.
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Pathology, Boston, MA 02215, USA. matkins@bidmc.harvard.edu
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Upton
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parker
authors.forename: Amanda
authors.initials: A
authors.lastname: Youmans
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000628:therapy; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2