Genetic diagnosis identifies occult lymph node metastases undetectable by the histopathological method.

TLDR

The mutant allele‑specific amplification (MASA) method can detect a single tumor cell with genetic changes amid thousands of normal cells. This study aimed to determine whether MASA could sensitively detect lymph node metastasis in colorectal cancer patients. To this end, 22 colorectal cancers were screened for K‑ras and p53 mutations, and the corresponding regional lymph nodes were examined genetically using MASA. K‑ras mutations were identified in six tumors and p53 mutations in nine, and in seven of 14 cases with genetic alterations the lymph nodes were genetically positive yet histologically negative, indicating that genetic evaluation may uncover occult metastases and serve as a prognostic indicator.

Abstract

The mutant allele-specific amplification (MASA) method is capable of detecting one tumor cell containing genetic changes in a sample containing thousands of normal cells. To investigate whether MASA can be applied to sensitive detection of lymph node metastasis, we screened 22 colorectal cancers for K-ras and p53 mutations and examined corresponding regional lymph node at the genetic level by the MASA method. Six of the primary tumors were found to certain K-ras mutations, and nine exhibited mutations of the p53 gene. In seven of the 14 cases in which genetic alterations were identified (mutations in both genes were found in one tumor), we found discrepancies between the genetic and the histopathological diagnoses with respect to the presence or absence of cancer cells in lymph nodes, in that these patients were histologically diagnosed lymph node negative, hn(-) but genetically diagnosed lymph node positive, gn(+). Because disease recurs in 20-30% of cancer patients whose lymph nodes are histopathologically negative after surgery, genetic evaluation of lymph nodes for metastasis may become a useful prognostic indicator.