Stereologic estimation of the total numbers, the composition and the anatomic distribution of lymphocytes in cone biopsies from patients with stage I squamous cell carcinoma of the cervix uteri

The aim of this study was to present a method to obtain basic biological data on the in situ cellular immune response towards cancer. Using stereology, we estimated the density and frequency of immune cells of 10 different phenotypes in cone biopsies from 20 patients with FIGO stage I cervical squamous cell carcinoma. The anatomic distribution of immune cells with respect to intraepithelial, periepithelial or stromal compartments was recorded in normal epithelium, dysplastic epithelium and carcinoma. We estimated the number of immune cells per cancer cell, and the 3D total number of immune cells, inside cancer tissue. The tumor volume was estimated in 3D and corrected for shrinkage occurring during tissue processing. We found more immune cells in cancer compared to dysplasia and normal epithelia. A median total number of 278 center dot 10(3) CD3+, 69.1 center dot 10(3) CD4+ and 113 center dot 10(3) CD8+ cells were present in the cancers. A median number of 63 CD3+, 11 CD4+ and 29 CD8+ cells were present per cancer cell. The average volume of tumors in stage IA was significantly smaller than that of stage IB. This method was found to be usable and of potential value in clinical pathology research, and for development and evaluation of immunotherapy.