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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Jul;86(7):626–630. doi: 10.1111/j.1349-7006.1995.tb02444.x

Detection of Hepatic Micrometastasis in Pancreatic Adenocarcinoma Patients by Two‐stage Polymerase Chain Reaction/Restriction Fragment Length Polymorphism Analysis

Soichiro Inoue 1, Akimasa Nakao 1, Yasushi Kasai 1,, Akio Harada 1, Toshiaki Nonami 1, Hiroshi Takagi 1
PMCID: PMC5920886  PMID: 7559078

Abstract

Hepatic metastasis and retroperitoneal recurrence generally are considered to be the two primary modes of recurrence in pancreatic cancer. The goal of this study was to determine if patients with pancreatic adenocarcinoma have hepatic and peritoneal micrometastasis at operation. Pancreatic adenocarcinomas are known to have a high incidence of K‐ras gene mutations. Liver tissue specimens were obtained from 30 patients (17 with pancreatic adenocarcinoma and 13 with other diseases) with a hiopsy needle at operation. Peritoneal washings were obtained during operation from 20 patients with pancreatic adenocarcinoma. Two‐stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K‐ras oncogene mutation at codon 12. Thirteen of 17 pancreatic adenocarcinoma patients had K‐ras gene mutations in the liver, whereas all 13 patients with other diseases did not. However, only two of 20 pancreatic adenocarcinoma patients revealed K‐ras gene mutation in peritoneal lavage fluids. These results indicate the feasibility of detecting hepatic micrometastasis in patients with pancreatic adenocarcinoma, and imply that PCR/ RFLP analysis may be of value in the diagnosis, treatment and follow‐up of hepatic metastasis of pancreatic adenocarcinoma.

Keywords: Pancreatic cancer, K‐ras, PCR/RFLP analysis, Micrometastasis

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REFERENCES

  • 1. ) Nakao , A. and Takagi , H.Isolated pancreatoduodenectomy for pancreatic head carcinoma using catheter bypass of the portal vein . Hepato-Gastroenterology , 40 , 426 – 429 ( 1993. ). [PubMed] [Google Scholar]
  • 2. ) Fortner , J. G.Regional pancreatectomy for cancer of the pancreas, ampulla, and other related sites. Tumor staging and results . Ann. Surg. , 199 , 418 – 425 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) Mansfield , V.PCR‐based approaches for detection of mutated ras genes . PCR Methods Appl. , 1 , 211 – 216 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Smit , V. T. , Boot , A. J. , Smits , A. M. , Fleuren , G. J. , Cornelisse , C. J. and Bos , J. L.KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas . Nucleic Acids Res. , 16 , 7773 – 7782 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Almoguera , C. , Shibata , D. , Forrester , K. , Martin , J. , Arnheim , N. and Perucho , M.Most human carcinomas of the exocrine pancreas contain mutant c‐K‐ras genes . Cell , 53 , 549 – 554 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Tada , M. , Omata , M. and Ohto , M.Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma . Gastroenterology , 100 , 233 – 238 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Lemoine , N. R. , Jain , S. , Hughes , C. M. , Staddon , S. L. , Maillet , B. , Hall , P. A. and Kloppel , G.Ki‐ras oncogene activation in preinvasive pancreatic cancer . Gastroenterology , 102 , 230 – 236 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Kahn , S. M. , Jiang , W. , Culbertson , T. A. , Weinstein , I. B. , Williams , G. M. , Tomita , N. and Ronai , Z.Rapid and sensitive nonradioactive detection of mutant K‐ras genes via ‘enriched’ PCR amplification . Oncogene , 6 , 1079 – 1083 ( 1991. ). [PubMed] [Google Scholar]
  • 9. ) Shibata , D. K. , Arnheim , N. and Martin , W. J.Detection of human papilloma virus in paraffin‐embedded tissue using the polymerase chain reaction . J. Exp. Med. , 167 , 225 – 230 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. ) Capon , D. J. , Seeburg , P. H. , McGrath , J. P. , Hayflick , J. S. , Edman , U. , Levinson , A. D. and Goeddel , D. V.Activation of Ki‐ras2 gene in human colon and lung carcinomas by two different point mutations . Nature , 304 , 507 – 513 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Shibata , D. , Alumoguera , C. , Forrester , K. , Dunitz , J. , Martin , S. E. , Cosgrove , M. M. , Perucho , M. and Arnheim , N.Detection of c‐K‐ras mutations in fine needle aspirates from human pancreatic adenocarcinomas . Cancer Res. , 80 , 622 – 626 ( 1990. ). [PubMed] [Google Scholar]
  • 12. ) Urban , T. , Ricci , S. , Grange , J. D. , Lacave , R. , Boudghene , F. , Breittmayer , F. , Languille , O. , Roland , J. and Bernaudin , J. F.Detection of c‐Ki‐ras mutations by PCR‐RFLP analysis and diagnosis of pancreatic adenocarcinomas . J. Natl. Cancer Inst. , 85 , 2008 – 2012 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Tada , M. , Omata , M. , Kawai , S. , Saisho , H. , Ohto , M. , Saiki , R. K. and Sninsky , J. J.Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma . Cancer Res. , 53 , 2472 – 2474 ( 1993. ). [PubMed] [Google Scholar]
  • 14. ) Watanabe , H. , Sawabu , N. , Ohta , H. , Satomura , Y. , Yamakawa , O. , Motoo , Y. , Okai , T. , Takahashi , H. and Wakabayashi , T.Identification of K‐ras oncogene mutations in the pure pancreatic juice of patients with ductal pancreatic cancers . Jpn. J. Cancer Res. , 84 , 961 – 965 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Hayashi , N. , Arakawa , H. , Nagase , H. , Yanagisawa , A. , Kato , Y. , Ohta , H. , Takano , S. , Ogawa , M. and Nakamura , Y.Genetic diagnosis identifies occult lymph node metastases undetectable by the histopathological method . Cancer Res. , 54 , 3853 – 3856 ( 1994. ). [PubMed] [Google Scholar]
  • 16. ) Grunewald , K. , Lyons , J. , Frohlich , A. , Feichtinger , H. , Weger , R. A. , Schwab , G. , Janssen , J. W. and Bartram , C. R.High frequency of Ki‐ras codon 12 mutations in pancreatic adenocarcinoma . Int. J. Cancer , 43 , 1037 – 1041 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Mariyama , M. , Kishi , K. , Nakamura , K. , Obata , H. and Nishimura , S.Frequency and types of point mutation at the 12th codon of the c‐Ki‐ras gene found in pancreatic cancers from Japanese patients . Jpn. J. Cancer Res. , 80 , 622 – 626 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Nagata , Y. , Abe , M. , Motoshima , K. , Nakayama , E. and Shiku , H.Frequent glycine‐to‐aspartic acid mutations at codon 12 of c‐Ki‐ras gene found in human pancreatic cancer in Japanese . Jpn. J. Cancer Res. , 81 , 135 – 140 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Ridanpaa , M. , Ragnhild , A. L. , Onfelt , A. , Fossa , S. , Borrensen , A. L. and Husgafvel‐Pursiainen , K.K‐ras oncogene codon 12 point mutations in testicular cancer . Environ. Health Perspect. , 101 , 185 – 187 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Anwar , K. , Nakakuki , K. , Naiki , H. and Inuzuka , M.ras gene mutations and HPV infection are common in human laryngeal carcinoma . Int. J. Cancer , 53 , 22 – 28 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Kuo , M. Y. P. , Jeng , J. H. , Chiang , C. P. and Hahn , L. J.Mutations of Ki‐ras oncogene codon 12 in betel quid chewing‐related human oral squamous cell carcinoma in Taiwan . J. Oral Pathol. Med. , 23 , 70 – 74 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Koshiba , M. , Ogawa , O. , Habuchi , T. , Hamazaki , S. , Shimada , T. , Takahashi , R. and Sugiyama , T.Infrequent ras mutations in human stomach cancers . Jpn. J. Cancer Res. , 84 , 163 – 167 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. ) Caldas , C. , Hahn , S. A. , Hruban , R. H. , Redston , M. S. , Yeo , C. J. and Kern , S. E.Detection of K‐ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia . Cancer Res. , 54 , 3568 – 3573 ( 1994. ). [PubMed] [Google Scholar]
  • 24. ) Motojima , K. , Urano , T. , Nagata , Y. , Shiku , H. , Tsunoda , T. and Kanematsu , T.Mutations in the Kirsten‐ras oncogene are common but lack correlation with prognosis and tumor stage in human pancreatic carcinoma . Am. J. Gastroenterol. , 86 , 1784 – 1788 ( 1991. ). [PubMed] [Google Scholar]

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