TY - JOUR
T1 - Detection of mutated K12-ras in histologically negative lymph nodes as an indicator of poor prognosis in stage II colorectal cancer
AU - Belly, Robert T.
AU - Rosenblatt, Joseph D.
AU - Steinmann, Michele
AU - Toner, Jacqueline
AU - Sun, Jianbo
AU - Shehadi, Joseph
AU - Peacock, James L.
AU - Raubertas, Richard F.
AU - Jani, Niraj
AU - Ryan, Charlotte K.
N1 - Funding Information:
This study was supported in part by a Johnson and Johnson Corporate Office of Science and Technology Postdoctoral Fellowship Grant to J. Sun. The authors would like to thank Diana Scott from the Department of Pathology at Strong Memorial Hospital for obtaining and sectioning the paraffin blocks used in this study.
PY - 2001/8
Y1 - 2001/8
N2 - 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 nodemetastasis 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 positivefor a K12-ras mutation in the primary tumor. Multiple lymph node samples from 38 of these 46 patients were examined bya 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 lymphnodes (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 withstage 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 useof adjuvant therapy is warranted.
AB - 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 nodemetastasis 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 positivefor a K12-ras mutation in the primary tumor. Multiple lymph node samples from 38 of these 46 patients were examined bya 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 lymphnodes (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 withstage 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 useof adjuvant therapy is warranted.
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U2 - 10.3816/CCC.2001.n.011
DO - 10.3816/CCC.2001.n.011
M3 - Article
C2 - 12445369
AN - SCOPUS:18344398895
SN - 1533-0028
VL - 1
SP - 110
EP - 116
JO - Clinical colorectal cancer
JF - Clinical colorectal cancer
IS - 2
ER -