The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes
Krpina K, Babarovic E, Dordevic G, Fuckar Z, Jonjic N. Croat Med J. 2012 Dec 15;53(6):598-604.


Kristian Krpina, Department of Urology, Clinical Hospital Center Rijeka, Tome Strizica 3, 51000 Rijeka, Croatia,


Aim. To evaluate whether tumor infiltrating lymphocytes (TIL) in biopsy specimens are associated with the clinical outcome of non-muscle invasive bladder cancer. Methods. We retrieved tumor specimens from 115 patients with solitary papillary non-muscle invasive bladder cancer treated between 1996 and 2006 and constructed tissue microarrays. Patients were divided in two groups: those with recurrent disease (N=69) and those without recurrent disease (N=46) during the follow up of minimum 5 years. All patients were treated with initial transurethral resection and none received adjuvant therapy. Immunhistochemical staining was performed with anti-CD3, CD4, CD8, and Granzyme B (GrB). The CD4+:CD8+ and GrB+:CD8 ratios were determined. Results. Tumor infiltrating lymphocytes were predominantly observed within cancer stroma, and only rare individual cells were observed intraepithelially. The group without recurrent disease had lower levels of CD3+ and CD8+ lymphocytes than the group with recurrent disease (P=0.0001, P=0.0002, respectively). The CD4+:GrB+ and GrB+:CD8+ ratios were significantly higher in patients without recurrent disease (P=0.0002, P=0.039, respectively). Conclusion. This study revealed a possible connection between TIL number and bladder cancer recurrence. TIL subset ratio showed different patterns in recurrent and non-recurrent tumors, which is why it could become a useful a prognostic clinical index if our findings are confirmed in randomized trials.