Minimal Residual Disease and Survival in UICC Stage I / II Colorectal Cancer
Abstracts
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Objective: 20 to 30 % of patients with stage I/II colorectal cancer die of recurrent disease. A possible explanation is the presence of minimal residual disease in histopathological tumor-free (pN0) lymph nodes, which can be detected by immunohistochemistry (IHC) or by the more sensitive RT-PCR. We investigated whether the detection of disseminated tumor cells is useful to identify patients with a colorectal carcinoma stage I / II which have a high risk for recurrent disease. Methods: Our study group consisted of 85 patients with a colorectal carcinoma UICC stage I/II, which were curatively resected (R0) at our department between 1988 and 1995, with a median follow-up time of 86 months. From each patient, 2 fresh frozen peritumoral lymph nodes, which were located nearest to the tumor site, were evaluated by CK-20 RT-PCR and IHC. The detection of CK-20 was correlated with histopathological parameters and prognosis. Results: CK-20 mRNA was expressed in the lymph nodes of 44 patients (52 %). Fifteen of the 18 patients, which developed tumor recurrence, expressed CK-20. IHC detected CK-20 positive cells in the lymph nodes of 24 patients (28%). The combined evaluation of RT-PCR and IHC revealed that the RT-PCR expression of 13 patients were caused by isolated extranodal IHC-positive tumor cells, which had no prognostic impact and were caused by contamination. These patients were defined as RT-PCR. The 5-year overall survival of the 31 patients with positive IHC-controlled CK-20 RT-PCR was 73 % compared to 96 % in the 54 patients with negative IHC-controlled CK-20 RT-PCR (p<0.001). Multivariate analysis identified IHC-controlled CK-20 RT-PCR as an independant prognostic factor. Conclusions: The combination of IHC and RT-PCR is a sensitive method for the detection of cytokeratin-positive cells and was proven to be of prognostic relevance. Confirmation of the presented data in further studies may lead to a subgroup identification of patients with colorectal carcinoma UICC stage I/II, which may profit of adjuvant therapy. |
