The expression profile of p14, p53 and p21 in tumour cells is associated with disease-specific survival and the outcome of postoperative chemotherapy treatment in muscle-invasive bladder cancer.

We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy.

We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival.

The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P = 0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03).

The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.

Urologic oncology. 2018 Oct 24 [Epub]

Firas Aljabery, Ivan Shabo, Oliver Gimm, Staffan Jahnson, Hans Olsson

Department of Urology, and Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, SE 581 85, Linköping, Sweden. Electronic address: ., Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery (MMK), Karolinska Institutet, SE 171 77, Stockholm, Sweden. Department of Breast, Endocrine and Sarcoma Surgery, Karolinska University Hospital, SE 171 76, Stockholm, Sweden., Department of Surgery and Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, SE 581 85, Linköping, Sweden., Department of Urology, and Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, SE 581 85, Linköping, Sweden., Department of Pathology and Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, SE 581 85, Linköping, Sweden.