KAI1 metastasis suppressor gene is frequently down-regulated in cervical carcinoma

KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. I t belongs to a structurally distinct family of cell surface glycoproteins. Decreased KAI1 expression has been observed in several common solid epithel ial tumors, including prostatic, pancreatic, lung, hepatic, colorectal, ova rian, and esophageal cancers. A recent study also observed frequent loss of KAI1 expression in a number of squamous cell carcinomas of the cervix by i mmunohistochemical technique. To further confirm whether this gene is alter ed in this malignancy, we analyzed KAI1 expression in various stages of cer vical carcinoma by a molecular method. Total cellular RNA was extracted fro m 84 primary invasive cervical carcinomas and 6 metastatic or recurrent les ions. cDNA was synthesized and was used for real-time quantitative polymera se chain reaction analysis. The level of KAII expression was obtained as th e value of threshold cycle (Ct) and was quantitated with a comparative Ct m ethod. In addition, paraffin blocks of the tumors were selected and prepare d for immunohistochemical study with an anti-KMI1 polyclonal antibody, C-16 . Both the realtime quantitative polymerase chain reaction method and immun ohistochemical study revealed a frequent decrease in KAI1 expression in Inv asive cervical cancers and metastatic or recurrent lesions. However, the re duction in KAI1 was not related to progression of the disease. When tumor c ell differentiation was analyzed, poorly differentiated tumors showed a gre ater decrease in KAI1 expression than well or moderately differentiated tum ors (P < 0.001). Histologically, KAI1 loss was observed equally in both squ amous cell carcinoma and adeno-/adenosquamous carcinoma. Since down-regulat ion of KAI1 occurs in both early and late stages of cervical cancer, we sug gest that its involvement in the progression of this malignancy is an early event.