Role of L1 cell adhesion molecule in gastric carcinoma.

56 Background: L1 cell adhesion molecule (L1) is a 200-220 kDa transmembrane glycoprotein of the immunoglobulin super family initially identified in neural cells. L1 was detected in ovarian cancer in a stage-dependent manner, was found exclusively in the invasion front of colorectal cancer, and has been considered a stem cell marker in glioma. The authors have shown that mRNA expression of L1 was a significant prognostic factor in gastric cancer (Kodera et al. Gastrointestinal Cancer Symposium 2009, abst 37). Its role in gastric cancer was further investigated. Methods: Expression of L1 was observed by immunostaining in 72 surgically resected pT4A-stage gastric cancer specimens. The association of L1 with peritoneal seeding and prognosis was elucidated. mRNA expression of L1-expressing gastric cancer cell line, KATO3, was suppressed using siRNA (KATO3 L1-). Microarray was used to indentify molecules that differ in expression between KATO3 L1- and the parental cell line. Results: L1 was scarcely stained in non-cancerous epithelial cells and intestinal metaplastic cells. L1 was detected mainly in the cell surface membrane of cancer cells in 15 of 72 specimens, more often in the intestinal type cancer. No correlation was found between L1 expression and detection of cancer cells in the peritoneal washes or development of peritoneal carcinomatosis. Nevertheless, the prognosis of L1-positive cancer was significantly inferior (p = 0.024). Prognosis was particularly poor among 6 cases where L1 was expressed in cancer cells at the invasive front (median survival time 149 days). Of 40,000 genes evaluated in the microarray, mRNA expression of 50 genes were amplified by > 4-fold whereas the expression of 20 genes were attenuated to less than 1/4. Of these, expression of DYRK1A that induces apoptosis in conjunction with p53 was markedly suppressed to less than 1/8. Suppression of DYRK1A in the KATO3 L1- in comparison with the parental cell line was confirmed by RT-PCR. Conclusions: L1 affects prognosis of gastric cancer, particularly when it is expressed in cancer cells at the invasion front. Its role in the biology of gastric cancer has began to be elucidated. No significant financial relationships to disclose.