Shomik Sengupta

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor.

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 8:00 am - 12:00 pm1 Apr 2005618: Costimulatory B7-H1 In Renal Cell Carcinoma Patients: Indicator of Tumor Aggressiveness and Potential Therapeutic Target R. Houston Thompson, Michael D. Gillett, John C. Cheville, Christine M. Lohse, Haidong Dong, W. Scott Webster, Kent G. Krejci, John R. Lobo, Shomik Sengupta, Lieping Chen, Horst Zincke, Michael L. Blute, Scott E. Strome, Bradley C. Leibovich, and Eugene D. Kwon R. Houston ThompsonR. Houston Thompson More articles by this author , Michael D. GillettMichael D. Gillett More articles by this author , John C. ChevilleJohn C. Cheville More articles by this author , Christine M. LohseChristine M. Lohse More articles by this author , Haidong DongHaidong Dong More articles by this author , W. Scott WebsterW. Scott Webster More articles by this author , Kent G. KrejciKent G. Krejci More articles by this author , John R. LoboJohn R. Lobo More articles by this author , Shomik SenguptaShomik Sengupta More articles by this author , Lieping ChenLieping Chen More articles by this author , Horst ZinckeHorst Zincke More articles by this author , Michael L. BluteMichael L. Blute More articles by this author , Scott E. StromeScott E. Strome More articles by this author , Bradley C. LeibovichBradley C. Leibovich More articles by this author , and Eugene D. KwonEugene D. Kwon More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34858-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "618: Costimulatory B7-H1 In Renal Cell Carcinoma Patients: Indicator of Tumor Aggressiveness and Potential Therapeutic Target." The Journal of Urology, 173(4S), p. 169 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 169 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information R. Houston Thompson More articles by this author Michael D. Gillett More articles by this author John C. Cheville More articles by this author Christine M. Lohse More articles by this author Haidong Dong More articles by this author W. Scott Webster More articles by this author Kent G. Krejci More articles by this author John R. Lobo More articles by this author Shomik Sengupta More articles by this author Lieping Chen More articles by this author Horst Zincke More articles by this author Michael L. Blute More articles by this author Scott E. Strome More articles by this author Bradley C. Leibovich More articles by this author Eugene D. Kwon More articles by this author Expand All Advertisement Loading ...

BACKGROUND: Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. METHODS: The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. RESULTS: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001) for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI: 0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P < 0.001). CONCLUSIONS: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.