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Genetic detection of colorectal cancer cells in circulation and lymph nodes

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Diseases of the Colon & Rectum

Abstract

PURPOSE: This study was undertaken to investigate the clinical implications of detection of genetic alterations in blood and lymph nodes in colorectal cancer patients. METHODS: The reverse transcriptase polymerase chain reaction product of the cytokeratin gene in blood was examined as a cancer cell-specific expression in 35 colorectal cancer patients. The K-ras or p53 gene mutations in the lymph nodes histopathologically negative for metastasis were studied by the mutant-allele-specific amplification method in 26 colorectal cancer patients. RESULTS; The reverse transcriptase polymerase chain reaction assay was able to detect a cytokeratin reverse transcriptase polymerase chain reaction product at a concentration from a single to ten colon cancer cells per 106 normal peripheral blood mononuclear cells. Cytokeratin reverse transcriptase polymerase chain reaction products were detected in nine patients' blood samples, although none of the samples were cytologically detectable. The blood's cytokeratin positivity correlated with the invasive mode of the tumor (P <0.05) and the presence of distant metastasis (P <0.01). Two (50 percent) of four patients whose blood was positive for cytokeratin had recurrences. Of 17 patients with the K-ras or p53 gene mutation in primary tumors, 9 (53 percent) had the corresponding mutations in lymph nodes. Mutation positivity in lymph nodes correlated with the presence of lymphatic invasion of the primary tumor (P <0.05). All patients with mutation-negative lymph nodes remained disease-free for more than two years after surgery. CONCLUSION: Detection of cytokeratin reverse transcriptase polymerase chain reaction products in the blood and K-ras or p53 gene mutations in the lymph nodes histologically negative for metastasis may be applicable for clinical use, despite some limitations, and may serve as a useful clinical factor for stratifying patients who are at high or low risk for recurrence after surgery.

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References

  1. Gastrointestinal Tumor Study Group. Adjuvant therapy of colon cancer—results of a prospectively randomized trial. N Engl J Med 1984;310:737–43.

    Google Scholar 

  2. National Institutes of Health Conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1447–50.

    Google Scholar 

  3. O'Connel MJ, Schaid DJ, Ganju V, Cunningham J, Kovach JS, Thibodeau ST. Current status of adjuvant chemotherapy for colorectal cancer. Cancer 1992;70:1732–9.

    PubMed  Google Scholar 

  4. Fidler IJ: The evolution of biological heterogeneity in metastatic neoplasms. In: Nicolson GL, Milas L, eds. Cancer invasion and metastasis: biologic and therapeutic aspects. New York: Raven Press, 1984:5–30.

    Google Scholar 

  5. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalogue of human cytokeratins: patterns of expression in normal epithelia, tumours and cultured cells. Cell 1982;31:11–24.

    PubMed  Google Scholar 

  6. Datta YH, Adams PT, Drobyski WR, Ethier SP, Terry VH, Roth MS. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol 1994;12:475–82.

    PubMed  Google Scholar 

  7. Krismann M, Todt B, Schröder J,et al. Low specificity of cytokeratin 19 reverse transcriptase-polymerase chain reaction analyses for detection of hematogenous lung cancer dissemination. J Clin Oncol 1995;13:2769–75.

    PubMed  Google Scholar 

  8. Soeth E, Röder C, Juhl H, Krüger U, Kremer B, Kalthoff H. The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerasechain reaction is related to the stage of disease. Int J Cancer 1996;69:278–82.

    PubMed  Google Scholar 

  9. Burchill SA, Bradbury MF, Pittman K, Southgate J, Smith B, Selby P. Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction. Br J Cancer 1995;71:278–81.

    PubMed  Google Scholar 

  10. Takeda S, Ichii S, Nakamura Y. Detection of K-ras mutation in sputum by mutant-allele-specific amplification (MASA). Hum Mutat 1993;2:1115–20.

    Google Scholar 

  11. Hayashi N, Arakawa H, Nagase H,et al. Genetic diagnosis identifies occult lymph node metastases undetectable by the histopathological method. Cancer Res 1994;54:3853–6.

    PubMed  Google Scholar 

  12. Hayashi N, Ito I, Yanagisawa A,et al. Genetic diagnosis of lymph-node metastasis in colorectal cancer. Lancet 1995;345:1257–9.

    PubMed  Google Scholar 

  13. Harmanek P, Sobin LH, eds. TNM classification of malignant tumors. 4th ed. Berlin: Springer-Verlag, 1987.

    Google Scholar 

  14. Maniatis T, Fritsh EF, Sanbrook J, eds. Molecular cloning: a laboratory manual. 1st ed. New York: Cold Spring Harbor Laboratory, 1982.

    Google Scholar 

  15. Miyoshi Y, Nagase H, Ando H,et al. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in APC gene. Hum Mol Genet 1992;1:229–33.

    PubMed  Google Scholar 

  16. Glavies D, Huben RP, Weiss L. Haematogenous dissemination of cells from human renal adenocarcinomas. Br J Cancer 1988;57:32–5.

    PubMed  Google Scholar 

  17. International (Ludwig) Breast Cancer Study Group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 1990;335:1565–8.

    Google Scholar 

  18. Cutait R, Alves VA, Lopes LC,et al. Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins. Dis Colon Rectum 1991;34:917–20.

    PubMed  Google Scholar 

  19. Mascarel I, Bonichon F, Coindre JM,et al. Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer 1992;66:523–7.

    PubMed  Google Scholar 

  20. Schoenfeld A, Luqmani Y, Smith D,et al. Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction. Cancer Res 1994;54:2986–90.

    PubMed  Google Scholar 

  21. Noguchi S, Aihara T, Nakamori S,et al. The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Cancer 1994;74:1595–600.

    PubMed  Google Scholar 

  22. Mori M, Mimorti K, Inoue H,et al. Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res 1995;55:3417–20.

    PubMed  Google Scholar 

  23. Bos JL. Ras oncogenes in human cancer: a review. Cancer 1989;49:4682–9.

    PubMed  Google Scholar 

  24. Levine AJ, Momand J, Finaly CA. The p53 tumor suppresser gene. Nature 1991;358:453–7.

    Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Surgery II, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565, Osaka, Japan

    Shoji Nakamori M.D.

  2. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan

    Masao Kameyama M.D., Hiroshi Furukawa M.D. & Shingi Imaoka M.D.

  3. Takara Advanced Biomedical Center, Japan

    Osamu Takeda B.S.

  4. Department of Genome Research, Cancer Institute, Japan

    Sachiko Sugai B.S.

  5. Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, Japan

    Yusuke Nakamura M.D.

  6. Department Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan

    Shoji Nakamori M.D., Masao Kameyama M.D., Hiroshi Furukawa M.D., Osamu Takeda B.S., Sachiko Sugai B.S., Shingi Imaoka M.D. & Yusuke Nakamura M.D.

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  1. Shoji Nakamori M.D.
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  2. Masao Kameyama M.D.
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  3. Hiroshi Furukawa M.D.
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  4. Osamu Takeda B.S.
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  5. Sachiko Sugai B.S.
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  6. Shingi Imaoka M.D.
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  7. Yusuke Nakamura M.D.
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Additional information

Supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a New 10-Year Strategy for Cancer Control, Japan.

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Nakamori, S., Kameyama, M., Furukawa, H. et al. Genetic detection of colorectal cancer cells in circulation and lymph nodes. Dis Colon Rectum 40 (Suppl 10), S29–S36 (1997). https://doi.org/10.1007/BF02062017

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  • DOI: https://doi.org/10.1007/BF02062017

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