Purpose: Little is known about the role of p53 pathway and tumour associated macrophage (TAM) in tumour stroma and their influence on progression of urinary bladder cancer (UBC). In this study, we investigate the role and interaction of TMA infiltration in relation to the expression of cell cycle proteins involved in cells senescence.
Materials and Methods: We prospectively studied patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tissue from paraffin-embedded cystectomy tumour samples were immunostained with M2-specific macrophage marker CD163, p14, p53, p21, p16, pRb and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumour stroma were analysed in relation to clinical data and outcome.
Results: The median age of the 103 patients was 70 years (range 51-87 years), and 80 (78%) were male. Pathological staging was pT1–T2 (organ confined) in 23 (22%) patients and T3-T4 (non-organ confined) in 80 (78%) patients. Lymph node metastases were found in 43 patients (42%). Individual P14 expressions as well as simultaneous expression of p14p16, p14p53 are significantly associated with higher MI; (p = 0.03), (p = 0.03) and (p = 0.03) respectively. Simultaneous high expression of p53 by tumor cells and TAM infiltration was associated with better CSS (p = 0.005).
Tumor cells response to interaction with the TAM in UBC might be affected by the tumor cells expression profile of cell cycle proteins involved in senescence. Our results provide indications that the genotropic and immunotropic profiles might interact and influence the biology and clinical outcome of UBC.