Immunohistochemical Study for Expression of p53, bcl-2 and Bax in Uterine Sarcoma

Chu, Hyung Sik; Kim, Jong Hyeok; Huh, Jooryung; Lim, So Dug; Na, Jun Hee; Koh, Chang Won; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun

Abstract

Uterine sarcomas are rare tumors with unpredictable prognosis, comprising about 3% of uterine cancers. Little is known of epidemiologic risk factors and similarly, little work has been performed assessing molecular alterations in sarcomas. Proteins encoded by p53, bcl-2 and bax genes are important regulators of programed cell death, hence apoptosis. Alterations in the expression of these apoptosis-related genes can contribute to the development of most of human cancers, as well as possibly influence the prognosis of the cancer patients. Using antibodies specific for the p53, bcl-2 and bax proteins in combination with immunohistochemical methods, we examined for the first time the expression of these genes in 19 cases of uterine sarcoma, managed at Asan Medical Center between June, 1989 and December, 1996, including 13 leiomyosarcomas, 4 endodermal stromal sarcomas and 2 malignant mixed mullerian tumors. Twelve patients had stage I disease and 7 stage III, and 9 patients had tumors with mitoses less than 10 per 10 HPF, and the others had those with mitoses equal to or more than 10 per 10 HPF. The results were evaluated by semiquantitative analysis as non-(0%), low(1~25%), moderate(26~75%) and high expressors(>76%), and the latter two were defined as tumors with overexpression. The immunoreactivity of bcl-2 and bax appeared in the cytoplasm, while that of p53 was localized solely in the nuclei. p53 immunostaining revealed 4 non-expressors, 7 low, 3 moderate and 5 high expressors, showing 42.1% rate of overexpression. Immunostaining of bcl-2 showed 13 non-expressors, 2 low, 1 moderate and 3 high expressors, resulting 21.1% rate of overexpression and that of bax showed 1 non-expressors, 4 low, 6 moderate and 8 high expressors, resulting 73.7% rate of overexpression. We could not find any significant correlation among the degrees of the expressions of these three proteins. The overexpression of these three proteins did not show any significant association with stage of disease or mitotic count of tumor. In conclusion, although apoptosis-related factors such as p53, bcl-2 and bax are strongly suggested to play a certain role in tumorigenesis of uterine sarcoma, the correlation among them and prognostic implications need further investigation.