IMMUNOPEROXIDASE STAINING FOR CYTOKERATINS 8 AND 18 IS VERY SENSITIVEFOR DETECTION OF OCCULT NODE METASTASIS OF COLORECTAL-CANCER - A COMPARISON WITH GENETIC-ANALYSIS OF K-RAS

Aims: Recent reports suggest that genetic examination of K-ras or p53 mutation is more sensitive for the detection of occult lymph node meta stasis in colorectal carcinomas than conventional examination by haema toxylin and eosin (H & E) staining or immunohistochemistry for gene pr oducts, The aim of this study was, first, to define the microscopic ch aracteristics of metastatic cancer cells in lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8 and 18, and, seco nd, to compare the detection rate of occult lymph node metastasis for immunohistochemical vs genetic methods, Methods and results: K-ras mut ations were first examined in primary tumours of seven cases which sho wed distant metastasis or local recurrence within 5 years of the initi al surgery in spite of the original reporting of no lymph node metasta sis by routine H & E staining. K-ras mutations were positive in three cases in primary tumours and lymph nodes, and the remaining four prima ry tumours were negative for p53 mutation as well as It-ms mutation. T herefore, genetic analysis of occult lymph node metastasis was uninfor mative. but occult metastasis was detected by cytokeratin staining in two of these four cases, Comparative study of cytokeratin-positive cel ls was performed on each of the 43 lymph nodes from three cases with K -ras mutations, Cancer cells were detected in 28 of the 43 lymph nodes (65.1%) by cytokeratin staining and in 10 of the 43 corresponding lym ph nodes (23.3%) by genetic analysis, Artefactual contamination by can cer cells was present in eight of the 28 cytokeratin positive lymph no des, and three of the eight nodes were genetically positive, Conclusio ns: This study suggests that cytokeratin immunohistochemistry is more sensitive and specific for the detection of occult lymph node metastas is than genetic diagnosis by K-ras mutation in cases with genetic alte rations as well as in cases without them.