title: Comparison of proliferation activity in breast carcinoma by flow cytometry analysis of S-phase and quantitative analysis of MIB-1.
abstract: The S-phase which assesses tumor proliferation has been considered to be an independent prognostic factor for breast carcinoma. Quantitative analysis of MIB-1 immunoreactivity is a newly recognized method of determining cellular proliferation that offers some advantages over flow cytometry when limited tumor tissue is available. However, it has been controversial whether there is a significant correlation between MIB-1 immunostaining and S-phase in defining proliferation activity in breast cancer. In order to explore the usefulness of MIB-1 as an additional proliferation parameter and a potential prognostic factor for breast cancer, we analyzed 94 cases of invasive ductal carcinoma of the breast by both flow cytometry (for S-phase and DNA ploidy) and quantitative MIB-1 immunohistochemical analysis using formalin-fixed paraffin-embedded tissue. MIB-1 staining was quantitatively analyzed by image analysis and by visual scoring. Forty-six cases were diploid by flow, while the remaining 48 cases were aneuploid tumors. T-test results indicated that S-phase means were significantly greater (p = 0.0001) in aneuploid cases (mean = 18) compared to diploid cases (mean = 7). MIB-1 means were also greater in aneuploid patients, but these differences were only marginally significant (p = 0.05). S-phase was positively correlated with MIB-1 (r = 0.36, p = 0.003 for image analysis and r = 0.34, p = 0.001 for visual scoring). ROC curve analysis indicated that MIB-1 quantitation is a good predictor of high S-phase (i.e., > 10 percent) in aneuploid cases. A MIB-1 cutoff value of 25 percent for image analysis achieved 82 percent specificity and 80 percent sensitivity for aneuploid high S-phase, while a MIB-1 cutoff value of 40 percent for visual scoring was 73 percent specific and 85 percent sensitive. However, in diploid cases, no comparable MIB-1 cutoffs could be achieved for detecting high S-phase. In summary, our study demonstrated that aneuploid breast carcinomas proliferate more aggressively than diploid tumors. Although linear correlation between MIB-1 and S-phase was weak, MIB-1 was considered to be a good predictor of high S-phase in aneuploid breast cancer patients, possibly due to a threshold effect. Image analysis and visual scoring of MIB-1 immunoreactivity appeared to be comparable in analyzing proliferative activity in breast cancer. Thus MIB-1 assessed by visual scoring may be a less expensive alternative to image analysis.
authors.affiliation: Department of Pathology, University of Florida Health Science Center, Jacksonville 32209, USA. sm@umc5.umc.ufl.edu
authors.forename: S
authors.initials: S
authors.lastname: Masood
authors.forename: M M
authors.initials: MM
authors.lastname: Bui
authors.forename: L
authors.initials: L
authors.lastname: Lu
mesh_terms: D000782:Aneuploidy; D034961:Antigens, Nuclear; D001324:Autoantigens; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D009687:Nuclear Proteins / Q000032:analysis*; D012372:ROC Curve; D016196:S Phase
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; D019394:Ki-67 Antigen; D009687:Nuclear Proteins