Original Paper 123 ©2003, European Journal of Histochemistry The antigen Ki-67, which is associated with cell proliferation, has been demonstrated to be useful in predicting the devel- opment of human tumors. The objective of this study was to evaluate the prognostic utility of this biomarker in pre-malig- nant and malignant lesions of the prostate. A total of 162 prostate biopsies taken from patients diagnosed for benign prostatic hyperplasia (BPH, n=49), low grade prostatic intra- epithelial neoplasia (LGPIN, n=53), high grade prostatic intra- epithelial neoplasia (HGPIN, n=25) and carcinoma (CAR, n=35), were studied. Immunohistochemistry for Ki-67 was carried out on all the samples and the number of labeled cells was semi-quantitatively evaluated (weak, moderate or intense). In the non-invasive lesions, the presence of Ki-67- positive cells in the luminal layer of the epithelium was evalu- ated qualitatively as positive or negative. The correlation between the immunolabeling for Ki-67 and the histological diagnosis showed highly significant differences between BPH and CAR, LGPIN and CAR and HGPIN and CAR, with no signif- icant differences being found among the other groups. Analysis of the immunolabeling in luminal cells of non-inva- sive lesions showed an increase in accordance with the increase in the degree of histological lesion, the greatest per- centage being obtained in the HGPIN lesions (88.0%), with significant differences among all the groups. Bearing in mind that Ki-67 is a prognostic biomarker for cell proliferation, our results demonstrating the immunolabeling of Ki-67 in the luminal compartment of non-invasive lesions having the potential to evolve to malignancy, may have prognostic impli- cations. Correspondence: Dra. Elisa Muñoz Torres, Department of Cellular Biology and Pathology, Faculty of Medicine, University of Salamanca, Avda. Campo Charro s/n. 37007 Salamanca, Spain. Phone: international +34.923.294400. Ext: 1859. Fax: international +34.923.294549. E-mail: emuto@gugu.usal.es Key words: Ki– 67, prostate, pre-malignant lesions, carcinoma, immunohistochemistry Paper accepted on January 31, 2003. European Journal of Histochemistry 2003; vol. 47 issue 2 [Apr-Jun]:123-128 Ki-67 immunolabeling in pre-malignant lesions and carcinoma of the prostate. Histological correlation and prognostic evaluation E. Muñoz,* F. Gómez,° J.I. Paz,* I.Casado,° J.M. Silva, § M.T. Corcuera,° M. J. Alonso° *Department of Cellular Biology and Pathology, University of Salamanca; °Department of Pathology, Institute of Health Carlos III, Madrid; § Department of Urology, University of Salamanca, Spain T he notion of pre-malignant lesions and the sequence of morphological changes that cul- minate in carcinoma has been well estab- lished in some organs, such as the breast (Lowell, 1987;Tavassoli et al., 1990), cervix (The 1988 Be- thesda system, 1989), skin (Frankel, 1987; Rywlin, 1988), etc. Indeed, the knowledge of these lesions with pre-cancerous potential has led to therapeutic decisions being taken based on the morphological identification of the pre-malignant lesions in some of these organs. Despite the fact that carcinoma of the prostate is the most common cancer in the male (Boring et al., 1993) and a myriad of studies having been carried out, knowledge about carcinogenesis of the prostate has still not been completely analyzed. In general, it is accepted that prostatic intraepithelial neoplasia (PIN), or duct-acinar dysplasia, is probably the most important precursor lesion of invasive cancer. These lesions can often be recognized in the prostate before the development of an invasive car- cinoma (Cohen et al., 2000). Bearing in mind that the best way to combat them is by early diagnosis, a full knowledge of the lesions with potential for malignant evolution of the prostate is extremely important. The study of prognostic factors or bio- markers in these lesions and their standardization could help to better understand the evolutionary sequence of the phenomena involved in prostate carcinogenesis. The expression of the human protein Ki-67 is associated with cell proliferation. During inter- phase, the antigen can only be detected within the nucleus, whereas in mitosis, the majority of the pro- tein is trans-located to the surface of the chromo- somes.The fact that Ki-67 protein is present during all the active phases of the cell cycle (G1, S, G2 and mitosis), and absent from the G0 phase, has made it an excellent marker for determining the growth fraction of a determined cell population (normal or tumoral) (Scholzen and Gerdes, 2000). Further-