Correlations between reduced expression of the metastasis suppressor gene KAI-1 and accumulation of p53 in uterine carcinomas and sarcomas.

Kangai (KAI)-1 (CD82) is a metastasis suppressor gene, which belongs to the family of tetraspanin proteins. A loss of KAI-1 expression is associated with the advanced stages of many human malignancies. The present study was designed to investigate the expression pattern of KAI-1 in the normal endometrium and uterine tumors and to correlate it with the expression of tumor suppressor protein p53. KAI-1 could be found in the normal endometrium throughout the menstrual cycle. Thirteen of 42 endometrial carcinomas demonstrated moderate KAI-1 expression, but low expression of p53. Twenty-nine of 42 endometrial carcinomas showed reduced or absent KAI-1 expression, which correlated with strong expression of p53 (p < 0.001). There were significant correlations between KAI-1 expression and histological type, e.g., 93% of endometrioid carcinomas displayed a low or moderate immunostaining for KAI-1, whereas nearly all of the serous/clear cell carcinomas were KAI-1 negative (p < 0.001); tumor grading, e.g., 73% of high grade tumors showed no KAI-1 expression (p < 0.001). Most of the investigated uterine sarcomas were negative for KAI-1, whereas they displayed a strong immunostaining for p53. In conclusion, KAI-1 and p53 show inverse expression. The reduced KAI-1 expression may be the result of dysregulated p53 function and could be an important step in the endometrial carcinogenesis.