Applicability of the Bethesda System 2001 to a public health setting.

BACKGROUND: The degree of applicability of the Bethesda System 2001 (TBS 2001) for cervicovaginal cytology to a public health setting is unknown, and extrapolations from available data are unwarranted. METHODS: A "before/after" study design was used to evaluate the impact of TBS 2001 on an organized, population-based screening program in northern Italy. Between 2003-2004, 6 cytology laboratories converted from TBS 1991 to TBS 2001. A set of screening indicators based on TBS 2001 (85,012 patients) were compared with those based on TBS 1991 (199,833 patients) by means of their laboratory- and patient age-standardized ratio with a 95% confidence interval (CI). RESULTS: The prevalence of cervical intraepithelial neoplasm (CIN)2-3/carcinoma was stable between the 2 populations. TBS 2001 had no effect on the unsatisfactory rate (1.99% vs. 2.03% for TBS 1991) nor on follow-up compliance rate (93.2% vs. 92.3%). The reporting rate of atypical squamous cells (ASC) decreased from 17.1 to 14.7 per 1000 (ratio, 0.86; 95% CI, 0.81-0.91), the total positivity rate from 31.1 to 29.0 per 1000 (ratio, 0.93; 95% CI, 0.90-0.97), and the ASC:SIL (squamous intraepithelial lesion) ratio from 1.38 to 1.16. Compared with the ASCUS (ASC of undetermined significance) reports of TBS 1991, the predictive value for CIN2-3/carcinoma decreased from 5.2 to 3.5% (ratio, 0.68; 95% CI, 0.48-0.93) among ASCUS reports, but increased from 5.1 to 17.2% (ratio, 3.41; 95% CI, 1.64-6.28) among ASC-cannot exclude high grade lesion (ASC-H) reports. ASC-H had a 5.01-fold (95% CI, 2.23-10.2) greater predictive value than ASCUS. CONCLUSIONS: TBS 2001 is applicable to cervical screening in a public health setting.

Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome.

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.