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We sought to develop an accurate colorectal cancer model in nude mice with stable local growth, tumor cell dissemination, and reproducible metastatic capacity. To this end, we orthotopically transplanted histologically intact human colorectal cancer tissue from 10 human patients into nude mice. After successful local tumor growth, tumor tissues were retransplanted as many as 9 times in serial passage. All specimens were transplanted using microsurgical techniques. Histologic, immunohistochemical, and polymerase chain reaction techniques were used to determine tumor growth rates and kinetics, development of regional lymph node and distant hepatic metastases, and the induction of minimal residual disease (MRD). Stable local tumor growth rates with variable growth kinetics were detected in 73.4% of all mice. The lymph node and hepatic metastasis rates were low, at 18.4% and 4.9%, respectively. MRD, as reflected by CK20 positivity of the bone marrow in animals with lymph node and hepatic metastases, was present in 22.2%. The orthotopic colorectal cancer model described here is feasible for the induction of reproducible local tumor growth but is limited by variable growth kinetics and the low rate of lymph node and hepatic metastases. Cytokeratin-positive cells indicative of MRD could be detected in the bone marrow of approximately 25% of the nude mice with metastases. The observed induction of MRD after orthotopic implantation of intact human colon cancer in animals with lymph node and hepatic metastases might be improved if established colon cancer cell lines were used.

Detection of Cytokeratin 20 (CK20) in the blood of gastric cancer patients is an indicator for disseminated tumor cells (DTC) and minimal residual disease (MRD). Even after curative resection DTC can be detected in different body compartments. These DTC are discussed to be a reason for a relapse of the disease. This study investigates the prognostic impact of DTC in the blood of gastric cancer patients. The blood of 63 patients with stomach cancer was screened for DTC by means of a CK20 RT-PCR immediately before surgical approach. 40/63 patients were curative resected (R0 = 63,5%). From 40 curative resected patients 15 were positive for CK20 (37,5%) and 25 were negative; after palliative resection 11/23 patients were positive for CK20 (47,8%). Overall survival in both curative and negative resected patients was significant better for those who were negative for CK20 (60,4% survival after 45 month) compared to those patients beeing positive for CK20 (27,2% survival after 45 month; p = 0,03 log rank). Subgroup analysis in curative resected patients only revealed a significant longer overall survival in CK20 negative patients compared to CK20 positive patients (86% vs. 40,4%; p = 0,03 log rank). Thus, expression of CK20 in blood of gastric cancer patients is an independent marker of prognosis.

Gastric cancer carries a poor prognosis even after curative resection (R0). Tumor progression in gastric cancer patients has been attributed to the persistence of disseminated tumor cells (DTC) in various body compartments as a sign of minimal residual disease, although the prognostic relevance of DTC is still unclear. In this study the prognostic relevance of DTC in the blood of gastric cancer patients was investigated.Venous blood samples of 70 cancer patients were taken intraoperatively before surgical manipulation and examined by reverse transcription-polymerase chain reaction (RT-PCR) for expression of cytokeratin 20 (CK20) as a marker for DTC. Tumor-related survival was analyzed using univariate and multivariate models assessing occurrence of DTC, residual tumor classification, and tumor stage. Median follow-up was 20 months (range 1-57 months).Twenty-eight of the 70 patients (40%) were CK20 positive. The prevalence of DTC in patients following R0 resection (15/41, 37%) was similar to that in patients with residual tumor (13/29, 45%, NS). Furthermore, expression of CK20 was independent of TNM stage. Univariate analysis of R0-resected patients revealed CK20 to be a marker for significantly shorter tumor-related survival (p = 0.0363). In a multivariate analysis, CK20 was an independent prognostic marker. Detection of CK20 had greatest impact for early tumor stages (T1 and T2, N0; p0.0032).Detection of DTC in venous blood of gastric cancer patients is an independent predictive marker of poor prognosis and thus could help to define patients for adjuvant therapy with this tumor entity.