Abstract
Cytologic examination of peritoneal lavage fluid is a useful predictor of peritoneal recurrence in gastric cancer. However, this technique is not overly sensitive and requires special abilities in the cytologist. In this study, telomerase activity was used to detect free cancer cells in peritoneal lavage fluid from patients with gastric cancer. In the first part, 12 lavage-fluid samples obtained from 12 patients with gastric cancer were analysed using the conventional telomeric repeat amplification protocol (TRAP) assay. Three of five patients with early gastric cancer had positive telomerase activity. These false-positive results may have been due to lymphocyte contamination. Furthermore, polymerase chain reaction inhibitors were also detected in the lavage-fluid samples. Therefore, we developed a novel method for elimination of haematopoietic cell and Taq polymerase inhibitors to increase the accuracy of the TRAP assay using immunomagnetic beads, which bind to most normal and neoplastic human epithelial cells. Telomerase activity was found in 10 of 20 (50%) lavage-fluid samples from patients with serosal or subserosal invasion. Cytologic examination was positive in nine of 20 (45%) samples. Both the telomerase activity and cytology were negative in all 14 patients without serosal or subserosal invasion. These results suggest that the TRAP assay combined with immunomagnetic beads might be useful for detection of free cancer cells in the peritoneal space in gastric cancer without the aid of an experienced cytologist. © 2000 Cancer Research Campaign
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References
Abe S, Yoshimura H, Tabara H, Tachibana M, Monden N, Nakamura T and Nagaoka S (1995) Curative resection of gastric cancer: limitation of peritoneal lavage cytology in predicting the outcome. J Surg Oncol 59: 226–229
Ahn MJ, Noh YH, Lee YS, Lee JH, Chung TJ, Kim IS, Choi IY, Kim SH, Lee JS and Lee KH (1997) Telomerase activity and its clinicopathological significance in gastric cancer. Eur J Cancer 33: 1309–1313
Baba H, Korenaga D, Okamura T, Saito A and Sugimachi K (1989) Prognostic factors in gastric cancer with serosal invasion. Univariate and multivariate analyses. Arch Surg 124: 1061–1064
Bando E, Yonemura Y, Takeshita Y, Taniguchi K, Yasui T, Yoshimitsu Y, Fushida S, Fujimura T, Nishimura G and Miwa K (1999) Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma. Am J Surg 178: 256–262
Bizer LS (1983) Adenocarcinoma of the stomach: current results of treatment. Cancer 51: 743–745
Bodnar AG, Kim NW, Effros RB and Chiu CP (1996) Mechanism of telomerase induction during T cell activation. Exp Cell Res 228: 58–64
Bonenkamp JJ, Songun I, Hermans J and van de Velde CJ (1996) Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer. Br J Surg 83: 672–674
Counter CM, Gupta J, Harley CB, Leber B and Bacchetti S (1995) Telomerase activity in normal leukocytes and in hematologic malignancies. Blood 85: 2315–2320
Dupont JB Jr, Lee JR, Burton GR and Cohn I Jr (1978) Adenocarcinoma of the stomach: review of 1,497 cases. Cancer 41: 941–947
Gaffey MJ, Mills SE, Swanson PE, Zarbo RJ, Shah AR and Wick MR (1992) Immunoreactivity for Ber-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas. Am J Surg Pathol 16: 593–599
Harley CB (1991) Telomere loss: mitotic clock or genetic time bomb?. Mutat Res 256: 271–282
Hermanek P, Scheibe O, Spiessl B and Wagner G (1987) TNM classification of malignant tumors: the new 1987 edition. Rontgen-Blatter 40: 200
Hiyama K, Hiyama E, Ishioka S, Yamakido M, Inai K, Gazdar AF, Piatyszek MA and Shay JW (1995a) Telomerase activity in small-cell and non-small-cell lung cancers. J Natl Cancer Inst 87: 895–902
Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, Murakami Y, Kodama T, Piatyszek MA, Shay JW and Matsuura Y (1995b) Telomerase activity in gastric cancer. Cancer Res 55: 3258–3262
Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek MA, Shay JW, Ishioka S and Yamakido M (1995c) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 155: 3711–3715
Hiyama E, Kodama T, Shinbara K, Iwao T, Itoh M, Hiyama K, Shay JW, Matsuura Y and Yokoyama T (1997) Telomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res 57: 326–331
Iitsuka Y, Kaneshima S, Tanida O, Takeuchi T and Koga S (1979) Intraperitoneal free cancer cells and their viability in gastric cancer. Cancer 44: 1476–1480
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL and Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266: 2011–2015
Kitamura K, Beppu R, Anai H, Ikejiri K, Yakabe S, Sugimachi K and Saku M (1995) Clinicopathologic study of patients with Borrmann type IV gastric carcinoma. J Surg Oncol 58: 112–117
Kodama Y, Sugimachi K, Soejima K, Matsusaka T and Inokuchi K (1981) Evaluation of extensive lymph node dissection for carcinoma of the stomach. World J Surg 5: 241–248
Kodera Y, Yamamura Y, Torii A, Uesaka K, Hirai T, Yasui K, Morimoto T, Kato T and Kito T (1996) Postoperative staging of gastric carcinoma. A comparison between the UICC stage classification and the 12th edition of the Japanese General Rules for Gastric Cancer Study. Scand J Gastroenterol 31: 476–480
Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T and Kato T (1999) Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol 72: 60–64
Koga S, Kaibara N, litsuka Y, Kudo H, Kimura A and Hiraoka H (1984) Prognostic significance of intraperitoneal free cancer cells in gastric cancer patients. J Can Res Clin 108: 236–238
Langford LA, Piatyszek MA, Xu R, Schold SC Jr and Shay JW (1995) Telomerase activity in human brain tumours. Lancet 346: 1267–1268
Latza U, Niedobitek G, Schwarting R, Nekarda H and Stein H (1990) Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelia. J Clin Pathol 43: 213–219
Nakanishi H, Kodera Y, Torii A, Hirai T, Yamamura Y, Kato T, Kito T and Tatematsu M (1997) Detection of carcinoembryonic antigen-expressing free tumor cells in peritoneal washes from patients with gastric carcinoma by polymerase chain reaction. Jpn J Cancer Res 88: 687–692
Oka M, Hirazawa K, Yamamoto K, Iizuka N, Hazama S, Suzuki T and Kobayashi N (1996) Induction of Fas-mediated apoptosis on circulating lymphocytes by surgical stress. Ann Surg 223: 434–440
Ordonez NG (1998) Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The MD Anderson experience and a critical review of the literature. Am J Clin Pathol 109: 85–89
Piatyszek MA, Kim NW, Weinrich SL, Hiyama K, Hiyama E, Wright WE and Shay JW (1995) Detection of telomerase activity in human cell and tumors by a telomeric repeat amplification protocol (TRAP). Methods Cell Sci 17: 1–15
Rhyu MS (1995) Telomeres, telomerase, and immortality. J Natl Cancer Inst 87: 884–894
Saji M, Westra WH, Chen H, Umbricht CB, Tuttle RM, Box MF, Udelsman R, Sukumar S and Zeiger MA (1997) Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid. Surgery 122: 1137–1140
Schofield K, D’Aquila T and Rimm DL (1997) The cell adhesion molecule, E-cadherin, distinguishes mesothelial cells from carcinoma cells in fluids. Cancer 81: 293–298
Schott A, Vogel I, Krueger U, Kalthoff H, Schreiber HW, Schmiegel W, Henne-Bruns D, Kremer B and Juhl H (1998) Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker. Ann Surg 227: 372–379
Suzuki T, Ochiai T, Hayashi H, Hori S, Shimada H and Isono K (1999) Peritoneal lavage cytology findings as prognostic factor for gastric cancer. Semin Surg Oncol 17: 103–107
Tahara H, Nakanishi T, Kitamoto M, Nakashio R, Shay JW, Tahara E, Kajiyama G and Ide T 1995a) Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res 55: 2734–2736
Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay JW, Ide T and Tahara E 1995b) Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin Cancer Res 1: 1245–1251
Watson JD (1972) Origin of concatemeric T7 DNA. Nature 239: 197–201
Wright WE, Shay JW and Piatyszek MA (1995) Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity. Nucleic Acids Res 23: 3794–3795
Yashima K, Vuitch F, Gazdar AF and Fahey TJ 3rd (1997) Telomerase activity in benign and malignant thyroid diseases. Surgery 122: 1141–1145
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Mori, N., Oka, M., Hazama, S. et al. Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads. Br J Cancer 83, 1026–1032 (2000). https://doi.org/10.1054/bjoc.2000.1408
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DOI: https://doi.org/10.1054/bjoc.2000.1408
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