title: Detection of mutated K12-ras in histologically negative lymph nodes as an indicator of poor prognosis in stage II colorectal cancer.
abstract: Stage II colorectal carcinoma is characterized by negative lymph node pathology as determined by conventional microscopic examination. These patients generally do not receive adjuvant therapy although 20%-30% will die from metastatic disease. To determine whether K-ras mutations at codon 12 could be used as a sensitive indicator of occult lymph node metastasis in stage II colon carcinoma, a retrospective study was performed using restriction endonuclease-mediated selective polymerase chain reaction (REMS-PCR) amplification. Of 106 colonic tumors analyzed, 46 were identified as positive for a K12-ras mutation in the primary tumor. Multiple lymph node samples from 38 of these 46 patients were examined by a sensitive nested PCR protocol for the presence of a K12-ras mutation. Of these 38 patients, 14 had 1 or more positive lymph nodes by PCR (37%) and 24 were negative for the mutation (63%). Of the 14 patients with a K12-ras mutation detected in lymph nodes, 8 died of the disease within 5 years (57%) compared to only 4 of the 24 patients with ras-negative lymph nodes (17%). The difference in time to death from disease, stratified using K12-ras status of lymph nodes, was statistically significant (P = 0.036; log-rank test). These results suggest K-ras mutation status of lymph nodes in patients with stage II colon cancer might identify a subgroup of patients who are more likely to develop recurrent and/or metastatic disease and benefit from adjuvant therapy. Larger studies are indicated to determine whether detection of K-ras mutation positivity in histologically negative lymph nodes portends a poor prognosis and to determine whether more aggressive use of adjuvant therapy is warranted.
authors.affiliation: Ortho-Clinical Diagnostics, Molecular Diagnostics Unit, 100 Indigo Creek Drive, Rochester, NY 14626, USA. rbelly@cldx.com
authors.forename: R T
authors.initials: RT
authors.lastname: Belly
authors.forename: J D
authors.initials: JD
authors.lastname: Rosenblatt
authors.forename: M
authors.initials: M
authors.lastname: Steinmann
authors.forename: J
authors.initials: J
authors.lastname: Toner
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Shehadi
authors.forename: J L
authors.initials: JL
authors.lastname: Peacock
authors.forename: R F
authors.initials: RF
authors.lastname: Raubertas
authors.forename: N
authors.initials: N
authors.lastname: Jani
authors.forename: C K
authors.initials: CK
authors.lastname: Ryan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D018572:Disease-Free Survival; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies