Loss of Smad4 protein expression and 18qLOH as molecular markers indicating lymph node metastasis in colorectal cancer—a study matched for tumor depth and pathology

Abstract

Chromosome 18q21 deletion and Smad4 protein inactivation have been reported as molecular markers predicting unfavorable outcome in colorectal cancers and, in a previous report, we recently revealed that these molecules are closely associated with distant metastasis, which is one of the clinical factors affecting postoperative survival. However, there has been no discussion as to how these molecules influence another clinical factor, namely, lymph node metastasis. In this report, we studied the significance of chromosome 18q deletion and loss of Smad4 protein expression in association with lymph node metastasis. Forty pairs of colorectal cancer specimens were studied; one group was positive for lymph node metastasis while the other was negative. We examined Smad4 protein expression level and chromosome 18q deletion in the two groups. Immunohistochemical staining revealed that more cases showed a weaker stain for Smad4 protein in the lymph node positive group compared with the negative group (P = 0.00075). Furthermore, a higher ratio of 18q21 deletion was observed in the lymph node positive group (P = 0.029). We revealed that chromosome 18q deletion and Smad4 protein inactivation are the essential molecular events in the process of lymph node metastasis.