Gastric Cancer

, Volume 10, Issue 4, pp 197–204 | Cite as

Genetic detection of free cancer cells in the peritoneal cavity of the patient with gastric cancer: present status and future perspectives

  • Yoshiyuki Fujiwara
  • Yuichiro Doki
  • Hirokazu Taniguchi
  • Itsuro Sohma
  • Shuji Takiguchi
  • Hiroshi Miyata
  • Makoto Yamasaki
  • Morito Monden
Review article

Abstract

The purpose of this review is to examine the current status and future perspectives of the molecular analysis of peritoneal lavage fluid in patients with gastric cancer. During the past 10 years, the polymerase chain reaction (PCR) has been applied for the molecular detection of free cancer cells in the abdominal cavity of patients with gastric cancer, and its clinical significance in establishing the presence of peritoneal dissemination has been assessed by several groups especially in Japan. The majority of these studies have confirmed the predictive value of the molecular detection of peritoneal metastasis and recurrence using peritoneal lavage fluid. Based on these findings, since April 2006, the genetic diagnosis of body fluids has been included in the Japanese Government public health insurance program for patients with solid tumors. However, there are still many obstacles to overcome before the genetic diagnosis of micrometastasis can be considered a routine laboratory assay. Here we review the importance of the molecular detection of cancer cells in the abdominal cavity, and the molecular techniques used for such diagnosis; we also provide some clinical examples to illustrate the value of molecular diagnosis.

Key words

Gastric cancer Peritoneal dissemination Micrometastasis Molecular biology RT-PCR TRC 

References

  1. 1.
    Dupont, JB, Lee, JR, Burton, GR, Cohn, I,Jr 1978Adenocarcinoma of the stomach: review of 1497 casesCancer419417PubMedCrossRefGoogle Scholar
  2. 2.
    Yamada, E, Miyaishi, S, Nakazato, H, Kato, K, Kito, T, Takagi, H,  et al. 1980The surgical treatment of cancer of the stomachInt Surg6538799PubMedGoogle Scholar
  3. 3.
    Bando, E, Yonemura, Y, Takeshita, Y, Taniguchi, K, Yasui, T, Yoshimitsu, Y,  et al. 1999Intraoperative lavage for cytological examination in 1297 patients with gastric carcinomaAm J Surg17825662PubMedCrossRefGoogle Scholar
  4. 4.
    Bonenkamp, JJ, Songun, I, Hermans, J, van de Velde, CJ 1996Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancerBr J Surg836724PubMedCrossRefGoogle Scholar
  5. 5.
    Koga, S, Kaibara, N, Iitsuka, Y, Kudo, H, Kimura, A, Hiraoka, H 1984Prognostic significance of intra-peritoneal free cancer cells in gastric cancer patientsJ Cancer Res Clin Oncol1082368PubMedCrossRefGoogle Scholar
  6. 6.
    Japanese Gastric Cancer Association1998Japanese classification of gastric carcinoma – 2nd English editionGastric Cancer11024PubMedCrossRefGoogle Scholar
  7. 7.
    Noura, S, Yamamoto, H, Ohnishi, T, Masuda, N, Matsumoto, T, Takayama, O,  et al. 2002Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistryJ Clin Oncol20423241PubMedCrossRefGoogle Scholar
  8. 8.
    Yoshioka, S, Fujiwara, Y, Sugita, Y, Okada, Y, Yano, M, Tamura, S,  et al. 2002Real-time rapid reverse transcriptase-polymerase chain reaction for intraoperative diagnosis of lymph node micrometastasis: clinical application for cervical lymph node dissection in esophageal cancersSurgery1323440PubMedCrossRefGoogle Scholar
  9. 9.
    Okada, Y, Fujiwara, Y, Yamamoto, H, Sugita, Y, Yasuda, T, Doki, Y,  et al. 2001Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assayCancer92205664PubMedCrossRefGoogle Scholar
  10. 10.
    Sugita, Y, Fujiwara, Y, Taniguchi, H, Mori, T, Ishii, T, Niwa, H,  et al. 2003Quantitative molecular diagnosis of peritoneal lavage fluid for prediction of peritoneal recurrence in gastric cancerInt J Oncol23141923PubMedGoogle Scholar
  11. 11.
    Kodera, Y, Nakanishi, H, Ito, S, Yamamura, Y, Fujiwara, M, Koike, M,  et al. 2005Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigenGastric Cancer81428PubMedCrossRefGoogle Scholar
  12. 12.
    Nakanishi, H, Kodera, Y, Torii, A, Hirai, T, Yamamura, Y, Kato, T,  et al. 1997Detection of carcinoembryonic antigen-expressing free tumor cells in peritoneal washes from patients with gastric carcinoma by polymerase chain reactionJpn J Cancer Res8868792PubMedGoogle Scholar
  13. 13.
    Nakanishi, H, Kodera, Y, Yamamura, Y, Ito, S, Kato, T, Ezaki, T,  et al. 2000Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric-cancer patients with real-time RT-PCR on the LightCyclerInt J Cancer894117PubMedCrossRefGoogle Scholar
  14. 14.
    Yonemura, Y, Fujimura, T, Ninomiya, I, Kim, BS, Bandou, E, Sawa, T,  et al. 2001Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNAClin Cancer Res7164753PubMedGoogle Scholar
  15. 15.
    Schmidt, P, Thiele, M, Rudroff, C, Vaz, A, Schilli, M, Friedrich, K,  et al. 2001Detection of tumor cells in peritoneal lavages from patients with gastrointestinal cancer by multiplex reverse transcriptase PCRHepatogastroenterology4816759PubMedGoogle Scholar
  16. 16.
    Kodera, Y, Nakanishi, H, Yamamura, Y, Shimizu, Y, Torii, A, Hirai, T,  et al. 1998Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytologyInt J Cancer7942933PubMedCrossRefGoogle Scholar
  17. 17.
    Kodera, Y, Nakanishi, H, Yamamura, Y, Kanemitsu, Y, Shimizu, Y, Hirai, T,  et al. 2002Quantitative detection of disseminated free cancer in peritoneal washes with real-time reverse transcriptase polymerase chain reactionAnn Surg235499506PubMedCrossRefGoogle Scholar
  18. 18.
    Cai, J, Ikeguchi, M, Tsujitani, S, Maeta, M, Liu, J, Kaibara, N 2001Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancerGastric Cancer46674PubMedCrossRefGoogle Scholar
  19. 19.
    Lee, E, Chae, Y, Kim, I, Choi, J, Yeom, B, Leong, AS 2002Prognostic relevance of immunohistochemically detected lymph node micrometastasis in patients with gastric carcinomaCancer94286773PubMedCrossRefGoogle Scholar
  20. 20.
    Fukagawa, T, Sasako, M, Mann, GB, Sano, T, Katai, H, Maruyama, K,  et al. 2001Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinomaCancer 159275360CrossRefGoogle Scholar
  21. 21.
    Morgagni, P, Saragoni, L, Scarpi, E, Zattini, PS, Zaccaroni, A, Morgagni, D,  et al. 2003Lymph node micrometastases in early gastric cancer and their impact on prognosisWorld J Surg2755861PubMedCrossRefGoogle Scholar
  22. 22.
    Maehara, Y, Yamamoto, M, Oda, S, Baba, H, Kusumoto, T, Ohno, S,  et al. 1996Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis of gastric cancerBr J Cancer73837PubMedGoogle Scholar
  23. 23.
    Macadam, R, Sarela, A, Wilson, J, MacLennan, K, Guillou, P 2003Bone marrow micrometastases predict early post-operative recurrence following surgical resection of oesophageal and gastric carcinomaEur J Surg Oncol294504PubMedCrossRefGoogle Scholar
  24. 24.
    Chen, XM, Chen, GY, Wang, ZR, Zhu, FS, Wang, XL, Zhang, X 2004Detection of micrometastasis of gastric carcinoma in peripheral blood circulationWorld J Gastroenterol108048PubMedGoogle Scholar
  25. 25.
    Mori, N, Oka, M, Hazama, S, Iizuka, N, Yamamoto, K, Yoshino, S,  et al. 2000Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beadsBr J Cancer83102632PubMedCrossRefGoogle Scholar
  26. 26.
    Sakakura, C, Takemura, M, Hagiwara, A, Shimomura, K, Miyagawa, K, Nakashima, S,  et al. 2004Overexpression of dopa decarboxylase in peritoneal dissemination of gastric cancer and its potential as a novel marker for the detection of peritoneal micrometastases with real-time RT-PCRBr J Cancer9066571PubMedCrossRefGoogle Scholar
  27. 27.
    Shimomura, K, Sakakura, C, Takemura, M, Takagi, T, Fukuda, K, Kin, S,  et al. 2004Combination of L-3-phosphoserine phosphatase and CEA using real-time RT-PCR improves accuracy in detection of peritoneal micrometastasis of gastric cancerAnticancer Res24111320PubMedGoogle Scholar
  28. 28.
    Mori, K, Suzuki, T, Uozaki, H, Nakanishi, H, Ueda, T, Matsuno, Y,  et al. 2007Detection of minimal gastric cancer cells in peritoneal washings by focused microarray analysis with multiple markers: clinical implicationsAnn Surg Oncol141694702PubMedCrossRefGoogle Scholar
  29. 29.
    Benevolo, M 1998Diagnostic and prognostic value of peritoneal immunocytology in gastric cancerJ Clin Oncol16340611PubMedGoogle Scholar
  30. 30.
    Vogel, P, Ruschoff, J, Kummel, S, Zirngibl, H, Hofstadter, F, Hohenberger, W,  et al. 1999Immunocytology improves prognostic impact of peritoneal tumour cell detection compared to conventional cytology in gastric cancerEur J Surg Oncol255159PubMedCrossRefGoogle Scholar
  31. 31.
    Nekarda, H, Gess, C, Stark, M, Mueller, JD, Fink, U, Schenck, U,  et al. 1999Immunocytochemically detected free peritoneal tumour cells (FPTC) are a strong prognostic factor in gastric carcinomaBr J Cancer796119PubMedCrossRefGoogle Scholar
  32. 32.
    Abe, N, Watanabe, T, Toda, H, Machida, H, Suzuki, K, Masaki, T,  et al. 2001Prognostic significance of carcinoembryonic antigen levels in peritoneal washes in patients with gastric cancerAm J Surg18135661PubMedCrossRefGoogle Scholar
  33. 33.
    Nishiyama, M, Takashima, I, Tanaka, T, Yoshida, K, Toge, T, Nagata, N,  et al. 1995Carcinoembryonic antigen levels in the peritoneal cavity: useful guide to peritoneal recurrence and prognosis for gastric cancerWorld J Surg191337discussion 137PubMedCrossRefGoogle Scholar
  34. 34.
    Yamamoto, M, Baba, H, Kakeji, Y, Endo, K, Ikeda, Y, Toh, Y,  et al. 2004Prognostic significance of tumor markers in peritoneal lavage in advanced gastric cancerOncology671926PubMedCrossRefGoogle Scholar
  35. 35.
    Wang, JY, Lin, SR, Lu, CY, Chen, CC, Wu, DC, Chai, CY,  et al. 2005Gastric cancer cell detection in peritoneal lavage: RT-PCR for carcinoembryonic antigen transcripts versus the combined cytology with peritoneal carcinoembryonic antigen levelsCancer Lett22312935PubMedCrossRefGoogle Scholar
  36. 36.
    Horibe, D, Ochiai, T, Shimada, H, Tomonaga, T, Nomura, F, Gun, M,  et al. 2007Rapid detection of metastasis of gastric cancer using reverse transcription loop-mediated isothermal amplificationInt J Cancer12010639PubMedCrossRefGoogle Scholar
  37. 37.
    Ishii, T, Fujiwara, Y, Ohnaka, S, Hayashi, T, Taniguchi, H, Takiguchi, S,  et al. 2004Rapid genetic diagnosis with the transcription-reverse transcription concerted reaction system for cancer micrometastasisAnn Surg Oncol1177885PubMedCrossRefGoogle Scholar
  38. 38.
    Ko, Y, Klinz, M, Totzke, G, Gouni-Berthold, I, Sachinidis, A, Vetter, H 1998Limitations of the reverse transcription-polymerase chain reaction method for the detection of carcinoembryonic antigen-positive tumor cells in peripheral bloodClin Cancer Res421416PubMedGoogle Scholar
  39. 39.
    Ko, Y, Grunewald, E, Totzke, G, Klinz, M, Fronhoffs, S, Gouni-Berthold, I,  et al. 2000High percentage of false-positive results of cytokeratin 19 RT-PCR in blood: a model for the analysis of illegitimate gene expressionOncology59818PubMedCrossRefGoogle Scholar
  40. 40.
    Goeminne, JC, Guillaume, T, Salmon, M, Machiels, JP, D'Hondt, V, Symann, M 1999Unreliability of carcinoembryonic antigen (CEA) reverse transcriptase-polymerase chain reaction (RT-PCR) in detecting contaminating breast cancer cells in peripheral blood stem cells due to induction of CEA by growth factorsBone Marrow Transplant2476975PubMedCrossRefGoogle Scholar
  41. 41.
    Mori, T, Fujiwara, Y, Sugita, Y, Azama, T, Ishii, T, Taniguchi, K,  et al. 2004Application of molecular diagnosis for detection of peritoneal micrometastasis and evaluation of preoperative chemotherapy in advanced gastric carcinomaAnn Surg Oncol111420PubMedCrossRefGoogle Scholar
  42. 42.
    Yamamoto, K, Shimada, S, Hirota, M, Yagi, Y, Matsuda, M, Baba, H 2005EIPL (extensive intraoperative peritoneal lavage) therapy significantly reduces peritoneal recurrence after pancreatectomy in patients with pancreatic cancerInt J Oncol2713218PubMedGoogle Scholar
  43. 43.
    Fujimoto, S, Shrestha, RD, Kokubun, M, Ohta, M, Takahashi, M, Kobayashi, K,  et al. 1988Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seedingAnn Surg2083641PubMedCrossRefGoogle Scholar
  44. 44.
    Hamazoe, R, Maeta, M, Kaibara, N 1994Intraperitoneal thermo-chemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of randomized controlled studyCancer73204852PubMedCrossRefGoogle Scholar
  45. 45.
    Armstrong, DK, Bundy, B, Wenzel, L, Huang, HQ, Baergen, R, Lele, S,  et al. 2006Intraperitoneal cisplatin and paclitaxel in ovarian cancerN Engl J Med3543443PubMedCrossRefGoogle Scholar
  46. 46.
    Sakuramoto, S, Sasako, M, Yamaguchi, T, Kinoshita, T, Fujii, M, Nashimoto, A,  et al. 2007Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidineN Engl J Med357181020PubMedCrossRefGoogle Scholar
  47. 47.
    Fujimura, T, Ohta, T, Kitagawa, H, Fushida, S, Nishimura, GI, Yonemura, Y,  et al. 1998Trypsinogen expression and early detection for peritoneal dissemination in gastric cancerJ Surg Oncol69715PubMedCrossRefGoogle Scholar
  48. 48.
    Yonemura, Y, Endou, Y, Fujimura, T, Fushida, S, Bandou, E, Kinoshita, K,  et al. 2001Diagnostic value of preoperative RT-PCR-based screening method to detect carcinoembryonic antigen-expressing free cancer cells in the peritoneal cavity from patients with gastric cancerANZ J Surg715218PubMedCrossRefGoogle Scholar
  49. 49.
    Oyama, K, Terashima, M, Takagane, A, Maesawa, C 2004Prognostic significance of peritoneal minimal residual disease in gastric cancer detected by reverse transcription-polymerase chain reactionBr J Surg9143543PubMedCrossRefGoogle Scholar
  50. 50.
    Ito, S, Nakanishi, H, Kodera, Y, Mochizuki, Y, Tatematsu, M, Yamamura, Y 2005Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patientsBr J Cancer9398692PubMedCrossRefGoogle Scholar

Copyright information

© International and Japanese Gastric Cancer Association 2007

Authors and Affiliations

  • Yoshiyuki Fujiwara
    • 1
  • Yuichiro Doki
    • 1
  • Hirokazu Taniguchi
    • 1
  • Itsuro Sohma
    • 1
  • Shuji Takiguchi
    • 1
  • Hiroshi Miyata
    • 1
  • Makoto Yamasaki
    • 1
  • Morito Monden
    • 1
  1. 1.Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversityJapan

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