Expression Of P16～(INK4A), CDK4 And Cyclin D1 Protein In Uterine Smooth Muscle Tumors

[ Objective ] Uterine leiomyomas are the most common benign smooth muscle tumors in women at reproductive age and occur in nearly 20%-40%. Uterine leiomyo-sarcomas are rare tumors, accounting for only about 1.3% of all uterine malignancies, and they usually exhibit an extremely malignant clinical course. However, there are some tumours which exhibit unusual morphological features or growth patterns that cause difficulty in their distinction from malignant neoplasms, thus, it's have great clinical significance that to search for specific molecular tumor markers for leiomyo-scarcomas. P16^INK4A, CDK4 and cyclin D1 proteins are important cell proliferation regulators. They are relative to happenings and developments of several kinds of tumors. But there are rare reports about their effects on uterine smooth muscle tumors.The expression of P16^INK4A,CDK4 and cyclin D1 proteins was examined in uterine smooth muscle tumors using SP immunohistochemical technique,and the transcription of P16^INK4A mRNA was examined using hybridization in situ, to investigate their functions with development of uterine smooth muscle tumors. The other purpose of this study is to find new assistant signs to distinguish leiomyosarcoma from leiomyoma and provide experimental basis for the diagnosis of clinical pathology.[Methods] The expression of P16^INK4A,CDK4 and cyclin D1 protein in 21 cases of uterine leiomyosarcoma, 34 cases of uterine leiomyoma and 22 cases of normal myometrium was detected by SP immunohistochemical technique,and the expression of P16^INK4A mRNA studied by in situ hybridization. Of the 34 cases of uterine leiomyoma,there were 10 cases of leiomyoma, 10 cases of multiple leiomyoma,5 cases of cellular leiomyoma,4 cases of bizarre leiomyoma,4 cases of leiomyoma with red degeneration and 1 case of leiomyoma with hyalinization and calcification.[Results] Positive rates of P16^INK4A protein in uterine leiomyosarcoma, leiomyoma and normal myometrium are 62%, 15%, 10% respectively. Positive rates of CDK4 protein in uterine leiomyosarcoma, leiomyoma and normal myometrium are 90%, 26%, 10% respectively. Positive rates of cyclin D1 protein in uterine leiomyosarcoma, leiomyoma and normal myometrium are 57%, 53%, 0%. The expressions of P16^INK4A and CDK4 are both significant different (P<0.05) between uterine leiomyosarcoma and leiomyoma. The expressions of P16^INK4A and CDK4 are significant different (P< 0.05) between multiple leiomyoma and leiomyosarcoma, cellular leiomyoma and leiomyosarcoma, bizarre leiomyoma and leiomyosarcoma, leiomyoma with red degeneration and leiomyosarcoma. There is no significant different between subtypes of leiomyoma. The expression of cyclin D1 are significant different (P<0.05) between leiomyosarcoma and normal myometrium, leiomyoma and normal myometrium. The hybridization in situ demonstrated that the expression of P16^INK4A mRNA was located in the plasma of tumor cell. The in situ hybridization result and the immunohistochemical result are similar.[ Conclusions ] The expressions of P16^INK4A and CDK4 protein in uterine leiomyosarcoma are significantly higher than their expressions in leiomyoma and normal myometrium, and may be closely correlated with the genesis and development of leiomyosarcoma. Combining immunohistochemical detection of p16^INK4A and CDK4 is helpful to distinguish leiomyosarcoma from leiomyoma. Overexpression of cyclin Dl in uterine leiomyosarcoma and leiomyoma is the proliferation sign of uterine smooth muscle cells.