| To investigate the relationship between the expression of hypoxia-inducible factor 1 a and the hypoxemic hypoxia possibly resulting in tumor hypoxia, which caused by chronic obstructive pulmonary disease (COPD) and the prognostic valve of COPD in patients with bladder transitional carcinoma (BTCC) by the retrospective analysis and immunohistochemical method.A total of 80 specimens of BTCC were obtained from the archives of the Department of Pathology, Central South University Xiangya No.2 Hospital, Hunan China between July 2003 and July 2005. Subjects were 43 men and 37 women with a mean age of 68.2 years old and median age 69.0 years old(range 51.0-88.0).37 patients had a Transurethral resection of bladder tumor(TUR-BT),13 patients had a complete radical cystectomy and 30 patients had a partial cystectomy. Subjects were 35 paients with COPD and 45 patients without COPD. All the specimens were bladder transitional carcinoma tissues confirmed by the pathologist. The tumors, according to the TNM of UICC(the sixth edition 2002) classification, comprised 44 Ta-T1 (non muscle invasive bladder transitional carcinoma) and 36 T2-T4(muscle invasive bladder transitional carcinoma); they were graded using the WHO criteria, comprised 30 I,27 II and 23 III. The size of tumor no more than 3cm is 48 patients, and 32 more than 3cm.42 cases were single tumor, and 38 cases were multiple tumor. All the patients were assessed by urine cytology and cystoscopy every 3 months for the first 2 years after the first resction, every 6 months for the next 2 years, and yearly thereafter. Analysing the clinicopathological variables of the 80 patients by retrospective method. The overall survival(OS), disease specific survival(DSS) and progression free survival(PFS) were analyzed with regard to clinicopathological variables such as the presence of COPD, results of pulmonary function test (PFT), serum hemoglobin level and smoking history using the Kaplan-Meier survival analysis. The log rank method was used to assess the differences between groups. A multivariate analysis was performed according to the Cox proportional hazards regression model. At the same time, HIF-1αprotein expression and location in the specimens was analyzed by immunohistochemical method. To explore the relationship between the expression of hypoxia-inducible factor 1 a and the COPD and the prognostic valve of COPD in patients with BTCC. 1. The median overall survival of patients with COPD from diagnosis was 26.0 months and 50.0 months without COPD(P<0.001); The median progression free survival of patients with COPD from diagnosis was 11.0 months and 17.0 months without COPD(P<0.001), both indicated a significantly different.2. The median overall survival of patients with normal PFT from was 47.5 months and 27.0 months with abnormal PFT (P<0.001), which indicated a significantly different.3.The median overall survival of patients with serum Hb<110g/L was 32.0 months and 44.0 months with serum Hb>110g/L (P<0.05); The median progression free survival of patients with serum Hb≤110g/L was 13.0 months and 18.0 months with serum Hb>110g/L (P<0.05), both indicated a significantly different.4. Group of patients with COPD comprised 0 the (-) expression of HIF-1α,1 the (+) expression of HIF-1α,22 the (++) expression of HIF-1α, and 12 the (+++) expression of HIF-1α; Group of patients without COPD comprised 22 the (-) expression of HIF-1α,15 the (+) expression of HIF-1α, 2 the (++) expression of HIF-1α, and 6 the (+++) expression of HIF-1α(P< 0.001), which indicated a significantly different. High levels positive expression of HIF-1αwere associated with BTCC of higher clinicopathological stage and histological grade(P<0.001). 5. As a result of the multivariate analysis, the COPD was an independent prognostic variable for overall survival, progression free survival and disease specific survival. The clinicopathological stage was an independent prognostic variable for overall survival and disease specific survival. The levels of HIF-la expression was an independent prognostic variable for progression free survival.1. Based the semi-quantitative assessment of the HIF-1α,the systematic hypoxia caused by the COPD may intensify the hypoxia in tissues of BTCC.2. There is a positive correlation between the level of HIF-1αexpression and the clinicopathological stage and histological grade. We can assess the prognosis of BTCC with COPD by analysing the expression of HIF-1α.3. COPD is an independent prognostic variable for BTCC.
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