Ki-ras codon 12 point and P53 mutations: a molecular examination of the main tumor, liver, portal vein, peripheral arterial blood and para-aortic lymph node in pancreatic cancer.
OBJECTIVE
Frequent P53 mutations and Ki-ras codon 12 point mutations have been reported in pancreatic cancer. Pancreatic cancer often recurs in the liver and/or lymph nodes shortly after a surgical resection. The purpose of this study is to elucidate the occurrence of microcirculating cancer cells and micrometastasis in pancreatic cancer.


METHODS
P53 mutations and Ki-ras codon 12 point mutations were examined in the main tumor, liver, portal vein, and peripheral arterial blood, and para-aortic lymph nodes of patients with pancreatic cancer using molecular examinations.


RESULTS
P53 mutations in the main tumor were present in nine (29%) of 31 patients with pancreatic cancer, whereas a Ki-ras codon 12 point mutation was evident in 18 (62%) of 29 examined patients. The peripheral arterial and portal vein blood and liver were positive for gene abnormalities in one (5%) of 21, in none (0%) of 19, and in one (1%) of 20, respectively. A P53 mutation in the main tumor was evident in none (0%) of seven stage I or II carcinomas and in nine (38%) of 24 stage III or IV cases, whereas a Ki-ras codon 12 point mutation was present in four (67%) of six stage I or II cases and in 14 (61%) of 23 stage III or IV cases. In addition, 15 (71%) of 21 patients with gene abnormalities (Ki-ras codon 12 point and/or p53 mutation) in the main tumor showed lymph node metastasis at surgery, whereas five (42%) of 12 without gene abnormalities did not demonstrate lymph node metastasis. Two (29%) of six patients with gene abnormalities in the main tumor and without metastatic disease at surgery developed liver metastasis within 6 months after surgery, whereas all five (100%) without the gene abnormalities and metastatic disease at surgery did not develop the metastasis, with the sensitivity being 100%, specificity 44%, the predictive value of the positive test 36%, and the predictive value of the negative test 100%. Two patients who had gene abnormalities in the para-aortic lymph node were free from histopathological metastasis and these two patients developed para-aortic lymph node metastasis within 6 months after surgery.


CONCLUSIONS
A molecular examination of Ki-ras codon 12 and p53 mutations therefore enables us to predict, to some degree, the occurrence of liver and lymph node metastasis in pancreatic carcinoma.
Yamaguchi
K
K
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Chijiiwa
K
K
Torato
N
N
Kinoshita
M
M
Tanaka
M
M
D000368:Aged; D001158:Arteries; D001790:Blood Physiological Phenomena; D003062:Codon; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000556:secondary; D008198:Lymph Nodes / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics*; D010220:Para-Aortic Bodies; D017354:Point Mutation; D011169:Portal Vein / Q000503:physiopathology; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D016159:Tumor Suppressor Protein p53