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 l iver 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 par a-aortic lymph nodes of patients with pancreatic cancer using molecular exa minations. RESULTS: P53 mutations in the main tumor were present in nine (29%) of 31 p atients with pancreatic cancer, whereas a Ki-ras codon 12 point mutation wa s 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 mut ation in the main tumor was evident in none (0%) of seven stage I or II car cinomas and in nine (38%) of 24 stage III or IV cases, whereas a Ki-ras cod on 12 point mutation was present in four (67%) of six stage I or II cases a nd in 14 (61%) of 23 stage III or IV cases. In addition, 15 (71%) of 21 pat ients with gene abnormalities (Ki-ras codon 12 point and/or p53 mutation) i n the main tumor showed lymph node metastasis at surgery, whereas five (42% ) of 12 without gene abnormalities did not demonstrate lymph node metastasi s. Two (29%) of six patients with gene abnormalities in the main tumor and without metastatic disease at surgery developed liver metastasis within 6 m onths 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 posit ive test 36%, and the predictive value of the negative test 100%. Two patie nts 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 t herefore enables us to predict, to some degree, the occurrence of liver and lymph node metastasis in pancreatic carcinoma. (C) 2000 by Am. Cell. of Ga stroenterology.