DIFFERENTIATION, PROLIFERATION AND APOPTOSIS LEVELS IN HUMAN LEIOMYOMA AND LEIOMYOSARCOMA

A comparative analysis of the differentiation pattern, the proliferati ve behaviour, and the level of apoptosis between human benign and mali gnant neoplasms of smooth-muscle (SM) tissue is lacking. The clinical, histopathological, immunochemical, and immunocytochemical features of leiomyomas (LM) and leiomyosarcomas (LMS) were investigated by a pane l of monoclonal antibodies specific for some differentiation markers o f SM tissue (SM myosin and alpha-actin, desmin, and SM22) and for mark ers of non-muscle tissue (vimentin and non-muscle myosin). Proliferati ng normal and neoplastic cells were identified by proliferating-cell n uclear antigen (PCNA)/Ki67 immunostainings and the apoptotic cells wer e revealed by means of the terminal-deoxynucleolidyltransferase-mediat ed dUTP nick-end labelling technique. Cel electrophoresis and Western blotting, performed with anti-(SM1/SM2 myosin isoform) antibody, indic ated quantitative differences between LMS and LM, which mirrored highe r positive to negative nuclear ratios for PCNA, Ki67 and apoptosis in malignant as opposed to benign neoplasms. With LM, however, a similar SM1 to SM2 ratio could be associated with different proliferation leve ls. Uterine, gastric and intestinal LMS displayed specific patterns of SM1/SM2 and/or non-muscle myosin expression that were not paralled by different levels of proliferation/apoptosis. While the level of PCNA/ Ki67 correlated with the level of apoptosis in normal SM tissues and L M, that of LMS did not. In vivo at the cellular level, LM and uterine LMS displayed a near-uniform SM tissue differentiation, whereas the ot her LMS displayed a lesser or a heterogeneous immunoreactivity. In vit ro, cultured LMS cells showed a limited and peculiar expression of SM myosin. In conclusion, there is no reciprocal relationship between deg ree of differentiation and the level of proliferation, as exemplified by the finding that the less differentiated intestinal LMS displays th e lowest proliferative behaviour and that the relatively more differen tiated gastric LMS/metastasis is more proliferative.