STOCKHOLM, SWEDEN (UroToday.com) - The purpose of this multi-institutional study was to evaluate the immunological response in relation to known molecular subtypes of urothelial carcinoma (UC), and also to evaluate the prognostic impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) in tissue specimens from UC patients. They used tissue microarrays on bladder tissues which were obtained by TURBT, and then analyzed, with antibodies, for CD3, CD8, FOXP3, CD68 and CD163. Using an immunohistochemistry and histology, they classified cases into: uro-basal, genomically unstable, and SCC-like classifier. The end points of this study were disease-specific survival (n=52, 25 events) and progression-free survival (n=180, 24 events).
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As one would expect, the molecular subtypes of UC showed different degrees of immunological response. SCC-like subtype revealed the strongest response, followed by genomically unstable subtype and the uro-basal subtype. The subtype-specific responses were independent of tumor stage, TILs, and TAMs. Levels of CD68+ TAMs were associated with progression-free survival in non-muscle invasive cases (HR=1.52, 95% CI, p=0.016) Moreover, they reported that high levels of infiltrating CD3+ TILs in muscle invasive cases, were significantly associated with improved disease-specific survival after cystectomy (p < 0.01). The strongest association to poor survival was reported for a high CD68/CD3 ratio (HR=7.73, 95% p < 0.001) after adjusting for clinical stage. The inherent molecular biology of cancer and host related factors, such as immune response, typically determine the oncological outcomes. Using known molecular subtypes of UC and immunological responses from the host, authors showed that the molecular subtypes of UC influence the anti-tumor immunological responses in both muscle invasive and non-muscle invasive UC. They concluded that independent of clinical stage, high macrophage/T-cell ratio (CD68/CD3) correlates with poor prognosis in bladder cancer patients.
Although their findings are yet to be validated by other institutions, CD68/CD3 ratio prior to cystectomy could potentially be useful information for patient counseling and for design of clinical trials.
Presented by G. Sjödahl at the 29th Annual European Association of Urology (EAU) Congress - April 11 - 15, 2014 - Stockholmsmässan - Stockholm, Sweden.
Lund University, Department of Oncology, Lund, Sweden
Written by Reza Mehrazin, MD, medical writer for UroToday.com