We analyzed human Mut-S-Homologon-2 expression in normal endometrial tissue (n = 15) and malignancies of the uterine corpus (n = 40). Human Mut-S-Homologon-2 protein was investigated immunohistochemically on frozen sections, using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). Human Mut-S-Homologon-2 labeling pattern was compared with the staining pattern of the proliferation marker Ki-67 in the same tumors. A human Mut-S-Homologon-2 immunoreactivity score (human Mut-S-Homologon-2-IRS: negative 0-1; weak 2-3; moderate 4-6; strong 8-12) for semiquantitative analysis of human Mut-S-Homologon-2 expression is presented. In normal endometrial tissue samples we found weak nuclear immunoreactivity for human Mut-S-Homologon-2 in 67%, whereas the remaining 33% were negative for human Mut-S-Homologon-2 (mean human Mut-S-Homologon-2-IRS 1.25 +/- 1.29). All malignancies of the uterine corpus analyzed revealed moderate to strong nuclear immunoreactivity (mean human Mut-S-Homologon-2-IRS 9.00, +/- 3.16). Human Mut-S-Homologon-2 staining was heterogeneous, with visual differences among individual tumor cells. Expression of human Mut-S-Homologon-2 protein was consistently and strongly upregulated in tumor cells of malignancies of the uterine corpus compared with normal endometrial tissue (human Mut-S-Homologon-2-PP p<0.001; human Mut-S-Homologon-2-IS p<0.001; human Mut-S-Homologon-2-IRS p<0.001). No statistically significant correlation in comparing the labeling patterns for human Mut-S-Homologon-2 with the labeling patterns for Ki-67 (mean percentage of Ki-67-positive tumor cells 22.00% +/- 17.20) was observed in malignancies of the uterine corpus (human Mut-S-Homologon-2-PP p=0.443; human Mut-S-Homologon-2-IS p=0.234; human Mut-S-Homologon-2-IRS p=0.173). Our findings indicate that human Mut-S-Homologon-2 is expressed in normal human endometrial tissue and that expression of human Mut-S-Homologon-2 may be of importance for the genetic stability of malignancies of the uterine corpus in vivo. (J Histochem Cytochem 47:113-118, 1999).