Loss of chromosome Y is unrelated to the composition of the tumor microenvironment and patient prognosis in muscle-invasive urothelial bladder cancers.

Background: Loss of chromosome Y (LOY) has recently been proposed to be associated with cancer aggressiveness, altered T-cell function, and poor prognosis in bladder carcinomas.

Methods: Chromosome Y was analyzed using fluorescence in-situ hybridization on a tissue microarray containing 2,071 urothelial carcinomas of the urinary bladder from male patients, including 487 patients who had undergone cystectomy for muscle-invasive disease and for whom follow-up data were available. Data on tumor microenvironment were obtained from a previous study.

Results: LOY was found in 26.0% of 1,704 analyzable cancers. In non-invasive cancers, LOY frequency was comparable in pTa G2 (22.8%) and pTa G3 (24.1%, p = 0.8036) carcinomas and slightly increased from pTa to pT2 - 4 carcinomas (23.1% for pTa and 27.2% for pT2 - 4) but these differences were not significant (p = 0.0794). In muscle-invasive cancers, LOY frequency slightly increased from pT2 (25.5%) to pT4 cancers (33.0%), but this association was not significant (p = 0.1814). Among pT2 - 4 cancers, LOY was associated with venous invasion (p = 0.0010) but unrelated to pT, pN, and L-status, as well as to overall, recurrence-free, and cancer-specific survival. Muscle-invasive urothelial carcinomas with and without LOY did not show significant differences in the number of CD8 positive lymphocytes, fraction of CD8 positive intraepithelial lymphocytes, number of macrophages and dendritic cells, and fraction of T helper and T regulatory cells.

Conclusion: The lack of a clear association of LOY with histopathological parameters of cancer aggressiveness, patient prognosis, and parameters describing the tumor microenvironment strongly argues against the driving role of LOY in bladder cancer progression and cancer-associated immune reactions.