Molecular staging of colorectal cancer: K-ras mutation analysis of lymph nodes upstages Dukes B patients.
OBJECTIVE
Multiple attempts have been made to improve the clinical/pathologic staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whether K-ras mutational status of regional nodes in patients with Dukes B2 colorectal cancer could be used to stage their disease more accurately.


METHODS
Using formalin-fixed, paraffin-embedded archival material, tumor samples were screened for K-ras mutations using a mutation-specific polymerase chain reaction method, followed by gel electrophoresis in a 96-well array. Patients with Dukes B2 tumors that have mutations in codon 12 or 13 of the K-ras gene were identified.


RESULTS
Mutational analysis of the lymph nodes from these patients revealed an 80 percent (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation-free nodes developed recurrence compared with 37.5 percent (6/16) with K-ras positive lymph nodes.


CONCLUSIONS
The data suggest that patients with Dukes B2 colorectal cancers that have mutations in codon 12 or 13 of the K-ras gene are at high risk for the development of nodal metastases. Mutational analysis of the lymph nodes identifies high-risk patients who should be considered for adjuvant chemotherapy. Therefore, K-ras mutational analysis should be considered for molecular staging of colorectal cancer.
Thebo
J S
JS
Ferguson-Blodgett Digestive Disease Institute, Grand Rapids, Michigan, USA.
Senagore
A J
AJ
Reinhold
D S
DS
Stapleton
S R
SR
D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000145:classification / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging / Q000379:methods*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D015996:Survival Rate
D017931:DNA Primers; D004273:DNA, Neoplasm