Detection of occult metastases in sentinel lymph nodes from colon cancer patients by K-ras mutation peptide nucleic acid clamp PCR.
OBJECTIVE
To identify colon cancer patients with occult lymph node metastases.


BACKGROUND
The prognostic value of regional lymph node (LN) metastases in colorectal cancer patients is well established. The disease recurrences nevertheless experienced by 20% to 30% of the LN negative patients suggest a potential for improvement in current LN diagnostics. We suspect that a subgroup of the patients that are LN negative by routine examination has occult LN metastases that are prognostically relevant.


METHODS
To identify these patients we applied ex vivo sentinel lymph node (SLN) mapping to colon cancer patients and analyzed the SLNs by a sensitive peptide nucleic acid clamp PCR (polymerase chain reaction) assay for K-ras mutations, using these mutations as a surrogate marker for tumor cells.


RESULTS
SLNs were identified in 158 (96%) of 164 prospectively recruited patients with localized colon cancer. Of the 158 patients with successful SLN mapping, 67 (42%) had K-ras mutations detected in their primary tumors. We analyzed the SLNs from these patients by peptide nucleic acid clamp PCR for K-ras mutations and found mutations in SLNs from 35 (52%) patients. At least one SLN from 14 (70%) of 20 patients with histologically proven regional LN metastases was positive for the K-ras mutation test. Interestingly, 21 (45%) of the 47 patients without known LN metastases had K-ras mutations detected in their SLNs.


CONCLUSIONS
Sensitive detection of K-ras mutations in SLNs from colon cancer patients indicates the presence of occult metastases with potential prognostic implications.
Oltedal
Satu
S
Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.
Gilje
Bjørnar
B
Kørner
Hartwig
H
Aasprong
Ole Gunnar
OG
Tjensvoll
Kjersti
K
Heikkilä
Reino
R
Smaaland
Rune
R
Nordgård
Oddmund
O
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D020135:Peptide Nucleic Acids; D016133:Polymerase Chain Reaction; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D020135:Peptide Nucleic Acids