Immunoperoxidase staining for cytokeratins 8 and 18 is very sensitive for detection of occult node metastasis of colorectal cancer: a comparison with genetic analysis of K-ras

Abstract

Aims: Recent reports suggest that genetic examination of K-ras or p53 mutation is more sensitive for the detection of occult lymph node metastasis in colorectal carcinomas than conventional examination by haematoxylin and eosin (H & E) staining or immunohistochemistry for gene products. The aim of this study was, first, to define the microscopic characteristics of metastatic cancer cells in lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8 and 18, and, second, to compare the detection rate of occult lymph node metastasis for immunohistochemical vs genetic methods.

Methods and results: K-ras mutations were first examined in primary tumours of seven cases which showed distant metastasis or local recurrence within 5 years of the initial surgery in spite of the original reporting of no lymph node metastasis by routine H & E staining. K-ras mutations were positive in three cases in primary tumours and lymph nodes, and the remaining four primary tumours were negative for p53 mutation as well as K-ras mutation. Therefore, genetic analysis of occult lymph node metastasis was uninformative, but occult metastasis was detected by cytokeratin staining in two of these four cases. Comparative study of cytokeratin-positive cells 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 lymph nodes (23.3%) by genetic analysis. Artefactual contamination by cancer cells was present in eight of the 28 cytokeratin positive lymph nodes, and three of the eight nodes were genetically positive.

Conclusions: This study suggests that cytokeratin immunohistochemistry is more sensitive and specific for the detection of occult lymph node metastasis than genetic diagnosis by K-ras mutation in cases with genetic alterations as well as in cases without them.