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Loss of heterozygosis on chromosome 18q21-23 and muscle-invasive bladder cancer natural history.

Research paper by Tommaso T Cai, Nicola N Mondaini, Daniele D Tiscione, Maurizio M Dal Canto, Raffaella R Santi, Riccardo R Bartoletti, Gabriella G Nesi

Indexed on: 02 Dec '15Published on: 02 Dec '15Published in: Oncology letters



Abstract

Loss of heterozygosis (LOH) on chromosome (Chr) 18q21-23 was reported to be one of the most common genetic alterations identified in bladder cancer. The current study aimed to determine the prognostic role of LOH on Chr 18q21-23 in patients diagnosed with muscle-invasive urothelial bladder carcinoma (MIBC). A total of 34 consecutive patients were enrolled in the present prospective study. LOH on Chr 18 was assessed by performing multiplex polymerase chain reaction on paired blood and tumour tissue samples from each patient. The following primers were used in the present study: D18S51, MBP LW and MBP H. These data were then compared with follow-up information. The main outcome measure was patient status at the end of the follow-up. Cox regression was used to evaluate the impact of each parameter on cancer-specific survival and the Kaplan Meier test for disease-free survival was plotted in order to estimate survival. Out of 34 patients, 18 (52.9%) exhibited ≥1 alteration in one of the loci analysed on chromosome 18, while 16 (47.1%) revealed no alterations. No correlation was identified with stage (P=0.18) or grade (P=0.06); however, LOH on Chr 18q21-23 was significantly associated with a lower recurrence-free probability (P<0.0001). Kaplan-Meier curves demonstrated a significant association between patient status at follow-up and LOH on Chr 18 (P<0.001). In addition, multivariate analysis identified LOH on Chr 18 (P<0.001) and stage (P=0.01) as independent survival predictors. Furthermore, artificial neural network analysis was consistent with the results of the multivariate analysis. In conclusion, the present study highlighted the role of LOH on Chr 18q21-23 in predicting the clinical outcome of patients with MIBC.