Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival
Rishi R. Sekara, Claire M. De La Callea, Dattatraya Patila, Sarah A. Holzmana, Yoram Bauma, Umer Sheikhb, Jonathan H. Huanga, Adeboye O. Osunkoyaa,b,d, Brian P. Pollackb,c,d, Haydn T. Kissicka, Kenneth Ogana, Viraj A. Mastera
a Department of Urology, Emory University School of Medicine, Atlanta, GA, USA;
b Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA;
c Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA;
d The Atlanta VA Medical Center, Decatur, GA, USA
Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival
Rishi R. Sekara, Claire M. De La Callea, Dattatraya Patila, Sarah A. Holzmana, Yoram Bauma, Umer Sheikhb, Jonathan H. Huanga, Adeboye O. Osunkoyaa,b,d, Brian P. Pollackb,c,d, Haydn T. Kissicka, Kenneth Ogana, Viraj A. Mastera
a Department of Urology, Emory University School of Medicine, Atlanta, GA, USA;
b Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA;
c Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA;
d The Atlanta VA Medical Center, Decatur, GA, USA
摘要 Objective: To examine the prognostic value of tumor major histocompatibility complex I (MHCI) expression on survival and recurrence in patients with clear cell renal cell carcinoma (RCC). Methods: Fifty-three patients that underwent nephrectomy at our institution for clear cell RCC (T1-T3) with ≥ 4 years of follow-up were queried from our nephrectomy database. Immunohistochemical staining for MHCI was performed on tumor specimens and MHCI expression was quantified with an automated image analysis technique. Patients were divided into high and low MHCI expression groups in order to study the relationship between MHCI expression and prognosis using the Kaplan-Meier method and log-rank test. Results: Overall survival and recurrence free survival were increased in the high MHCI expression group compared to the low MHCI expression group (log-rank, p=0.036 and p=0.028, respectively). Patients alive at the end of the study had higher MHCI expression (mean positivity score 0.82) than those that died of disease (mean positivity score 0.76, t test, p=0.030). Patients that did not develop recurrence during the study period had higher MHCI expression (mean positivity score 0.83) than those that did develop recurrence (mean positivity score 0.78), but this difference was not significant (t test, p=0.079). Conclusion: Our data demonstrate that high MHCI expression confers improved overall and recurrence free survival in patients with clear cell RCC and could serve as an important prognostic tool in identifying high-risk patients.
Abstract: Objective: To examine the prognostic value of tumor major histocompatibility complex I (MHCI) expression on survival and recurrence in patients with clear cell renal cell carcinoma (RCC). Methods: Fifty-three patients that underwent nephrectomy at our institution for clear cell RCC (T1-T3) with ≥ 4 years of follow-up were queried from our nephrectomy database. Immunohistochemical staining for MHCI was performed on tumor specimens and MHCI expression was quantified with an automated image analysis technique. Patients were divided into high and low MHCI expression groups in order to study the relationship between MHCI expression and prognosis using the Kaplan-Meier method and log-rank test. Results: Overall survival and recurrence free survival were increased in the high MHCI expression group compared to the low MHCI expression group (log-rank, p=0.036 and p=0.028, respectively). Patients alive at the end of the study had higher MHCI expression (mean positivity score 0.82) than those that died of disease (mean positivity score 0.76, t test, p=0.030). Patients that did not develop recurrence during the study period had higher MHCI expression (mean positivity score 0.83) than those that did develop recurrence (mean positivity score 0.78), but this difference was not significant (t test, p=0.079). Conclusion: Our data demonstrate that high MHCI expression confers improved overall and recurrence free survival in patients with clear cell RCC and could serve as an important prognostic tool in identifying high-risk patients.
Rishi R. Sekar, Claire M. De La Calle, Dattatraya Patil, Sarah A. Holzman, Yoram Baum, Umer Sheikh, Jonathan H. Huang, Adeboye O. Osunkoya, Brian P. Pollack, Haydn T. Kissick, Kenneth Ogan, Viraj A. Master. Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival[J]. Asian Journal of Urology, 2016, 3(2): 75-81.
Rishi R. Sekar, Claire M. De La Calle, Dattatraya Patil, Sarah A. Holzman, Yoram Baum, Umer Sheikh, Jonathan H. Huang, Adeboye O. Osunkoya, Brian P. Pollack, Haydn T. Kissick, Kenneth Ogan, Viraj A. Master. Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival. Asian Journal of Urology, 2016, 3(2): 75-81.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
[2]
Ramsey S, Lamb GW, Aitchison M, McMillan DC. Prospective study of the relationship between the systemic inflammatory response, prognostic scoring systems and relapse-free and cancer-specific survival in patients undergoing potentially curative resection for renal cancer. BJU Int 2008;101:959-63.
[3]
Ljungberg B. Prognostic markers in renal cell carcinoma. Curr Opin Urol 2007;17:303-8.
[4]
Osunkoya AO, Grignon DJ. Practical issues and pitfalls in staging tumors of the genitourinary tract. Semin Diagn Pathol 2012;29:154-66.
[5]
Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:655-63.
[6]
Novara G, Ficarra V, Antonelli A, Artibani W, Bertini R, Carini M, et al. Validation of the 2009 TNM version in a large multi-institutional cohort of patients treated for renal cell carcinoma:are further improvements needed? Eur Urol 2010; 58:588-95.
[7]
Ng CS, Novick AC, Tannenbaum CS, Bukowski RM, Finke JH. Mechanisms of immune evasion by renal cell carcinoma:tumor-induced T-lymphocyte apoptosis and NFkappaB suppression. Urology 2002;59:9-14.
[8]
Rink M, Chun FK, Robinson B, Sun M, Karakiewicz PI, Bensalah K, et al. Tissue-based molecular markers for renal cell carcinoma. Minerva Urol Nefrol 2011;63:293-308.
[9]
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313:1960-4.
[10]
Galon J, Pages F, Marincola FM, Thurin M, Trinchieri G, Fox BA, et al. The immune score as a new possible approach for the classification of cancer. J Transl Med 2012;10:1.
[11]
Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011;29:610-8.
[12]
Kitamura H, Honma I, Torigoe T, Asanuma H, Sato N, Tsukamoto T. Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma. J Urol 2007;177:1269-72.
[13]
Brasanac D, Muller CA, Muller GA, Hadzi-Dzokic J, Markovic-Lipkovski J. HLA class I antigens expression in renal cell carcinoma:histopathological and clinical correlation. J Exp Clin Cancer Res 1999;18:505-10.
[14]
Holzman SA, de la Calle CM, Kissick HT, Osunkoya AO, Pollack BP, Patil D, et al. High expression of major histocompatibility complex class I in clear cell renal cell carcinoma is associated with improved prognosis. Urol Int 2015;95:72-8.
[15]
Yuan J, Liu S, Yu Q, Lin Y, Bi Y, Wang Y, et al. Down-regulation of human leukocyte antigen class I (HLA-I) is associated with poor prognosis in patients with clear cell renal cell carcinoma. Acta Histochem 2013;115:470-4.
[16]
Pollack BP, Sapkota B, Boss JM. Ultraviolet radiation-induced transcription is associated with gene-specific histone acetylation. Photochem Photobiol 2009;85:652-62.
[17]
Pollack BP, Sapkota B, Cartee TV. Epidermal growth factor receptor inhibition augments the expression of MHC class I and II genes. Clin Cancer Res 2011;17:4400-13.
[18]
Sapkota B, Hill CE, Pollack BP. Vemurafenib enhances MHC induction in BRAF homozygous melanoma cells. Oncoimmunology 2013;2:e22890.
[19]
Luboldt HJ, Kubens BS, Rubben H, Grosse-Wilde H. Selective loss of human leukocyte antigen class I allele expression in advanced renal cell carcinoma. Cancer Res 1996;56:826-30.
[20]
Atkins D, Ferrone S, Schmahl GE, Storkel S, Seliger B. Downregulation of HLA class I antigen processing molecules:an immune escape mechanism of renal cell carcinoma? J Urol 2004;171:885-9.
[21]
Lampen MH, van Hall T. Strategies to counteract MHC-I defects in tumors. Curr Opin Immunol 2011;23:293-8.
[22]
Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally:immunostimulation by anticancer drugs. Nat Rev Drug Discov 2012;11:215-33.
[23]
Lindsey KR, Rosenberg SA, Sherry RM. Impact of the number of treatment courses on the clinical response of patients who receive high-dose bolus interleukin-2. J Clin Oncol 2000;18:1954-9.
[24]
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54.
Christopher Hartman, Nikhil Gupta, David Leavitt, David Hoenig, Zeph Okeke, Arthur Smith. Advances in percutaneous stone surgery[J]. Asian Journal of Urology, 2015, 2(1): 26
-32
.
