Detektion von Cytokeratin-20 positiven Zellen ist ein unabhängiger Prognosefaktor bei nodal negativen kolorektalen Karzinomen — RT-PCR oder Immunhistochemie?

Abstract

Introduction:We showed in an initial study that RT-PCR detection of Cytokeratin-20 mRNA in lymph nodes of colorectal cancer can be used for identification of patients with a high risk of recurrence. We increased our study group and performed additional immunohistochemical staining for morphological evaluation of the RT-PCR results because of low specificity for RT-PCR detection published in the literature and in our series. Material and Method: Two peritumoral lymph nodes each from 85 patients with curatively resected colorectal carcinomas of stages I and II, operated upon between August 1988 and February 1995, were analyzed by CK-20 RT-PCR and immunohistochemistry (IHC), using the monoclonal antibody CK-20. The median follow-up was 86 months. Results: The detection rate for CK-20 mRNA was 52% (44 of 85 patients). Fifteen of 18 patients who developed tumor recurrences were CK-20-positive by RT-PCR. The sensitivity of this method was 83% and the specificity was 57%. Immunohistochemistry identified CK-20-positive cells in the lymph nodes of 24 patients (28%). In addition, 34% of cases had evidence of CK-20-positive cells outside the lymph-node capsule, which had no prognostic impact and were interpreted as contamination. An immunohistochemically controlled RT-PCR evaluation led to the exclusion of 13 patients with positive RT-PCR detection and isolated extranodal positive IHC. Specificity was increased to 75%. The 5-year recurrencefree survival of 31 patients with positive IHC-controlled RT-PCR evaluation was 61% compared with 94% in the 54 patients with negative RT-PCR ( p<0.001). CK-20 RT-PCR was the strongest prognostic factor in multivariate analysis. Conclusion: The detection of CK- 20 mRNA in lymph nodes of colorectal cancer stages I and II is an independent prognostic factor. The immunohistochemical control of CK-20 RT-PCR leads to identification of tumor cell contamination and improvement of specificity.