Nm23-H1 expression in multisteps of cervical carcinogenesis and the clinical significance of its high expression inintraepithelial neoplasia and early-stage squamous cell carcinoma of the uterine cervix

• Main Authors: Po-Hui Wang, 王博輝
• Other Authors: Long-Yau Lin, Ph.D
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/83690103589517783362

博士 === 中山醫學大學 === 醫學研究所 === 92 === To evaluate the expression of nm23-H1 protein in normal, precancerous and cancerous tissues of the uterine cervix and its role in cervical carcinogenesis, 86 cervical specimens, including 30 squamous cell carcinomas (SCC), 3 adenocarcinomas, one clear cell carcinoma; 19 high- and 13 low-grade squamous intraepithelial lesions (HSILs and LSILs) and 20 normal samples, were stained using an immunohistochemical method with streptavidin-biotin peroxidase immunostaining. Among the 30 SCC cases, the relationships between immunohistochemical expression of nm23-H1 and various clinicopathological characteristics for early-stage cervical cancer were evaluated. The cumulative recurrence hazard of these patients were also assessed. The Chi-square and Fisher’s exact tests, as well as Chi-square test for trends, were used for comparing nm23-H1 expression among normal, LSIL, HSIL and cancerous tissues. Fisher’s exact test was also used to determine the relationship between nm23-H1 immunoreactivity and the clinicopathologic variables, such as age (≥ 50 or < 50 years old), grade of differentiation (well, moderate or poorly differentiated), depth of stromal invasion ( ≥ 1/2 or < 1/2 of stromal depth), and metastatic status (lymph nodal, parametrial or vaginal variants). Subjects were further subdivided into low and high nm23-H1 expression groups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard. The log-rank test was then used to compare the recurrence distributions for different nm23-H1 expression groups over time. There were significant differences in levels of nm23-H1 expression between LSIL and HSIL (P = 0.016) and between LSIL and SCC (P = 0.002), but not between HSIL and SCC or normal and LSIL samples. Furthermore, a positive relationship was demonstrated for high nm23-H1 protein expression and degree of malignant transformation (P < 0.05). Among various clinicopathological characteristics, only deep stromal invasion ( ≥ 1/2 of stromal depth) was significantly associated with high nm23-H1 expression. Moreover, a high cumulative recurrence hazard was demonstrated for the high nm23-H1 expression group. In conclusion, high nm23-H1 expression may induce the cellular proliferation for the progression from low to high-grade intraepithelial lesions, with the subsequent emergence of invasive carcinoma, as well as deep stromal invasion and be used as a prognostic indicator.