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Correlation of tumor-infiltrating lymphocytes with bladder cancer recurrence in patients with solitary low-grade urothelial carcinoma

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Abstract

The aim of the present study was to correlate tumor-infiltrating lymphocytes (TIL) with bladder cancer recurrence in patients with solitary low-grade non-muscle-invasive bladder cancer (NMIBC). We retrospectively identified from the institutional database 115 patients with solitary low-grade NMIBC after transurethral resection (TURBT) without adjuvant therapy and with complete follow-up, between 1996 and 2006. Tumor specimens were retrieved and tissue microarrays were constructed. Patients were divided in two groups: those who developed recurrent disease (n = 69) and those without recurrence (n = 46) during a follow-up period of a minimum of 5 years. Immunohistochemical staining for TIL with anti-CD3, CD4, CD8, CD20, CD56, CD68, and granzyme B (GrB) was performed. Student’s t test, Mann–Whitney U test, as well as uni- and multivariate analyses were applied to compare the two patient groups. TIL were predominantly observed in cancer stroma. The number of CD3+ and CD8+ lymphocytes observed in the non-recurrent group of patients was lower than that in recurrent patients (p = 0.0001, p = 0.0002, respectively). Also, in uni- and multivariate analyses, levels of CD3+ TIL (OR = 5.4035; p = 0.0001 and OR = 5.8280; p = 0.0102) and CD8+ TIL (OR = 3.2857; p = 0.0036 and OR = 5.3257; p = 0.0092) showed prognostic value with regard to NMIBC recurrence. Our results suggest that CD3+ and CD8+ TIL are predictive of bladder cancer recurrence in patients with solitary low-grade NMIBC which might facilitate identification of patients with higher risk of recurrence. However, prospective validating studies have to confirm these results before immunohistochemical staining for CD3 and CD8 TIL can be included in the clinical workup of these patients.

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Abbreviations

AUC:

Area under the curve

CD:

Cluster of differentiation

CI:

Confidence interval

HR:

Hazard ratio

NMIBC:

Non-muscle-invasive bladder cancer

OR:

Odds ratio

TIL:

Tumor-infiltrating leukocytes

TURBT:

Transurethral resection of bladder tumor

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Acknowledgments

We would like to express our gratitude to Ozren Štanfel, Ankica Brajenić, and Ivan Dašek for the excellent technical assistance.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Urology, Clinical Hospital Center Rijeka, T. Strižića 3, 51000, Rijeka, Croatia

    Kristian Krpina

  2. Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta, 20, 51000, Rijeka, Croatia

    Emina Babarović & Nives Jonjić

Authors
  1. Kristian Krpina
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  2. Emina Babarović
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  3. Nives Jonjić
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Correspondence to Kristian Krpina.

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Krpina, K., Babarović, E. & Jonjić, N. Correlation of tumor-infiltrating lymphocytes with bladder cancer recurrence in patients with solitary low-grade urothelial carcinoma. Virchows Arch 467, 443–448 (2015). https://doi.org/10.1007/s00428-015-1808-6

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  • DOI: https://doi.org/10.1007/s00428-015-1808-6

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