Distinction of low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions based on quantitative analysis of proliferative activity

Abstract

The management of cervical dysplasia is determined by the grade of SIL (LSIL, conservative management; HSIL, ablative/excisional therapy). The grading, however, is subjective and its reproducibility is low. This study evaluates if quantitative differences in mitotic activity and MIB-1 expression (ME) in LSIL and HSIL are helpful in their discrimination. Twenty-seven cervical biopsies with LSIL and 16 with HSIL were immunostained for MIB-1. ME was evaluated in 100 contiguous cells of lesional squamous epithelium in basal layer, lower-third, middle-third, and upper-third, in areas with highest staining. Mitoses were counted in 10 contiguous high power fields in areas with the highest mitotic activity (mitotic index, MI). MI was significantly increased in HSIL (mean 27.5) as compared to LSIL (mean 14.3). MI at cut-off values < or =10 and > or =25, favored a diagnosis of LSIL, and HSIL, respectively. ME, in all four layers, was significantly greater in HSIL vs. LSIL. ME in the basal and the upper-third layer proved useful in grading SIL with equivocal MI: all LSIL cases with MI >10 had <30% of ME in the basal layer; and all, except one, had <30% of ME in the upper-third; all, except one HSIL cases with MI <25 had >30% of ME in either the basal or the upper-third layer. MI and ME (percentage) appear helpful in grading equivocal SIL cases.