Immunohistochemical Study on nm23 Protein Expression in Carcinoma of the Uterine Cervix

Park, Mi Young; Yun, Won Hi; Yoo, Jin A; Chae, Lim; Kim, Su Yeon; Kim, Seung Cheol; Ahn, Jung Ja; Woo, Bock Hi; Han, Woon Sup

Abstract

The nm23 gene was originally identified by differential screening of a cDNA library with RNA from low and high metastatic clones of a murine melanoma cell line. And the nm23 gene has been represented as a metastasis suppressor gene. The product of nm23 gene is known to be identical to nucleoside diphosphate(NDP) kinase. The lack of expression of nm23 protein has been correlated with a poorer prognosis in some human tumors, among which are breast carcinoma, malignant melanoma, gastric carcinoma and hepatcelluar cacin-oma. However, in several types of malignant tumors such as colon carcinoma, neuroblastoma and pancreatic carcinoma, unexpected overexpression of nm23 protein was found as compared with normal tissues. Also in a few studies with cervical carcinoma, the expression of nm23 protein was found to be increased as compared with normal cervical tissue recently. Therefore, in this study, we analyzed the expression of nm23-H1 protein by immunohistochemistry method in a series of 40 cervical carcinomas, to determine whether the alterations in the expression of nm23-H1 protein occured in cervical carcinoma as compared with cervical intraepithelial neoplasia(CIN) and normal cervices, and also analyzed the possible association between nm23 protein expression and prognostic parameters of cervical carcinoma at Ewha Womans University Mokdong Hospital from September 1993 to March 1997. The results obtained were as follows; 1. The mean ages of normal control patients, CIN and cervical carcinomas were 42.9 (+/-5.1) years, 39.5(+/-7.7) years, and 49.3(+/-11.7) years respectively. All cases of cervical carcinoma were squamous cell carcinomas. And the number of each stages Ia, Ib, IIa, IIb, III and IV were 13 cases, 8 cases, 6 cases, 9 cases, 2 cases, and 2 cases respectively. 2. In cervical carcinoma, nm23-H1 protein expression was significantly increased as compared with CIN and normal cervical tissue(t=5.017>1.96). 3. In cervical carcinoma, the nm23-H1 protein expression was more increased in higher stages(p=0.021). But it had no significant correlations with primary tumor size, lymphovascular space invasion, parametrial invasion or lymph node metastasis. Our results on nm23-H1 protein expression in cervical carcinoma suggest that cervical carcinoma seems to belong to the group of tumors, like colon carcinoma and neuroblastoma, pancreatic carcinoma in which nm23-H1 overexpression is associated with a more malignant phenotype. In this study, nm23-H1 protein was more expressed in higher clinical stages of cervical carcinoma. Therefore the expression of nm23-H1 protein probably may have a prognostic significance in cervical carcinoma. But a further prospective study on a larger population is needed to establish the role of nm23 gene in this kind of tumor.