ObjectiveTo evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies. Summary Background DataPreviously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients. MethodsFindings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer.The success of surgical treatment in patients with gastric and colorectal cancer is often limited. This is because of local recurrence or the development of distant metastases or peritoneal carcinosis by cells that have already been seeded at the time of operation but cannot be detected using conventional diagnostic tools. The elimination of these micrometastatic cells is the aim of various adjuvant therapies," 2 and obviously it would be helpful to detect minimal residual disease.Using immunocytologic methods, which are significantly more sensitive than conventional cytology,3 it has become possible to detect disseminated tumor cells in the bone marrow of patients with breast cancer,4 small cell lung No comprehensive immunocytologic studies exist concerning the prognostic significance of isolated intraperitoneal tumor cells. Therefore, we extended our former study

AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis. METHODS Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were i n v e s t i g a t e d b y i m m u n o s t a i n i n g w i t h biotinylated mab KL-1 and by RT-PCR using CK20 specific primers. RESULTS There were totally 9 of 16 surgical s p e c i m e n s g r o w i n g i n n u d e m i c e subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tu m o r . I n t h e g r o u p o f f r e s h t u m o r tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically transplanted tumors resemble the original tumor morphologically and biologically, including T A A e x p r e s s i o n s u c h a s C E A b y immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR. CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new d i a g n o s t i c m e t h o d s a n d t h e r a p e u t i c s t r a t e g i e s f o r m e t a s t a s e s i n c l u d i n g micrometastases.