Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma

The primary aim of this study was to investigate the expression of apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine leiomyosarcoma in order to identify molecular pathways that possibly could be important in the development of leiomyosarcoma. A secondary aim was to examine if the apoptotic and cell cycle regulatory protein expression profile of uterine leiomyosarcoma is potentially useful for clinical prognostic purposes.

A tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine leiomyomas was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53 using standard techniques. Staining was scored 0-12 for each marker, 0-3 being negative and 4-12 positive. Outcome analyses were performed only for leiomyosarcomas. First recurrence was determined from the time of initial diagnosis. Survival was determined from the time of initial diagnosis to last follow-up.

Associations were found between disease type (leiomyosarcoma vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54% vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a univariate analysis. In a multivariate analysis, tumor stage was the only independent significant prognostic factor (P = 0.002).

The significant differential expression of apoptotic and cell cycle regulatory proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors suggests that pathways involving these proteins may be important in the development of malignant disease and, therefore, could be potential targets for molecular therapies.