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Detection of Occult Metastasis in Lymph Nodes From Colorectal Cancer Patients: A Multiple-Marker Reverse Transcriptase-Polymerase Chain Reaction Study

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Diseases of the Colon & Rectum

INTRODUCTION

Lymph node status is a key factor for disease staging and is the main determinant for adjuvant therapy of colorectal cancer. The current staging procedure is unable to identify occult metastasis in lymph nodes, which is likely to be an important cause of treatment failure in some early-stage patients. The detection of occult metastasis could identify a patient subgroup at risk for disease relapse that would benefit from adjuvant therapy. The purpose of this study was to establish and test a multimarker reverse transcriptase-polymerase chain reaction assay for the molecular detection of occult metastases in lymph nodes.

METHODS

Forty-four patients with colorectal cancer and 14 patients with benign bowel diseases undergoing colonic resection were enrolled in the study. Reverse transcriptase-polymerase chain reaction was used to detect expression of three epithelial markers, carcinoembryonic antigen, cytokeratin 20, and guanylyl cyclase C, in fresh colorectal lymph node tissue.

RESULTS

Forty-six of 47 (97.9 percent) histologically positive lymph nodes were also positive by reverse transcriptase-polymerase chain reaction. Of 221 histologically negative nodes, 97 (43.9 percent) were positive for at least one of the three markers by reverse transcriptase-polymerase chain reaction: 24.9 percent for carcinoembryonic antigen, 16.7 percent for cytokeratin 20, and 24.9 percent for guanylyl cyclase C. Among these were 13 of 20 stage I and II cases, implying a staging shift to stage III by molecular diagnosis of occult metastasis. Fifty-nine additional nodes were found to be positive for occult metastases in 22 of 24 stage III and IV patients.

CONCLUSIONS

These results indicate that occult metastases are detectable by reverse transcriptase-polymerase chain reaction in histologically negative lymph nodes from colorectal cancer. The use of a panel of three markers improves the specificity of the method.

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REFERENCES

  1. AM Cohen S Tremiterra F Candela HT Thaler ER Sigurdson (1991) ArticleTitlePrognosis of node positive colon cancer Cancer 67 1859–61

    Google Scholar 

  2. GT Deans TG Parks BJ Rowlands RA Spence (1992) ArticleTitlePrognostic factors in colorectal cancer Br J Surg 79 608–13

    Google Scholar 

  3. Koyama Y, Kotake K, eds. Japanese Society for Cancer of the Colon and Rectum: a multi-institutional registry of large bowel cancer in Japan. Vol. 1-12 (1-6 in Japanese and 7-12 in English). Tochigi: Registry Committee, 1985–1996

  4. InstitutionalAuthorNameInternational Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators (1999) ArticleTitleEfficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer J Clin Oncol 17 1356–63

    Google Scholar 

  5. B Gusterson (1991) ArticleTitleAre micrometastasis clinically relevant? Br J Hosp Med 47 247–8

    Google Scholar 

  6. G Adell B Boeryd B Franlund R Sjodahl L Hakansson (1996) ArticleTitleOccurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes B colorectal carcinoma: an immunohistochemical study Eur J Surg 162 637–42

    Google Scholar 

  7. R Cutait VA Alves LC Lopes et al. (1991) ArticleTitleRestaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins Dis Colon Rectum 34 917–20

    Google Scholar 

  8. JK Greenson CE Isenhart R Rice C Mojzisik D Houchens EW Martin SuffixJr (1994) ArticleTitleIdentification of occult micrometastases in pericolic lymph nodes of Dukes’ B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49: correlation with long-term survival Cancer 73 563–9

    Google Scholar 

  9. MD Jeffers GM O’Dowd H Mulcahy M Stagg DP O’Donoghue M Toner (1994) ArticleTitleThe prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal carcinoma J Pathol 172 183–7

    Google Scholar 

  10. N Hayashi H Arakawa H Nagase et al. (1994) ArticleTitleGenetic diagnosis identifies occult lymph node metastases undetectable by histopathological method Cancer Res 54 3853–6

    Google Scholar 

  11. N Yamamoto Y Kato A Yanagisawa H Ohta T Takahashi T Kitagawa (1997) ArticleTitlePredictive value of genetic diagnosis for cancer micrometastasis: histologic and experimental appraisal Cancer 80 1393–8

    Google Scholar 

  12. M Mori K Mimori H Inoue et al. (1995) ArticleTitleDetection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction Cancer Res 55 3417–20

    Google Scholar 

  13. GJ Liefers AM Cleton-Jansen CJ Velde Particlevan de et al. (1998) ArticleTitleMicrometastases and survival in stage II colorectal cancer N Eng J Med 339 223–8

    Google Scholar 

  14. J Gunn JL McCall K Yun PA Wright (1996) ArticleTitleDetection of micrometastases in colorectal cancer patients by K19 and K20 RT-PCR Lab Invest 75 611–6

    Google Scholar 

  15. S Dorudi E Kinrade NC Marshall R Feakins NS Williams SA Bustin (1998) ArticleTitleGenetic detection of lymph node micrometastases in patients with colorectal cancer Br J Surg 85 98–100

    Google Scholar 

  16. M Futamura Y Takagi H Koumura et al. (1998) ArticleTitleSpread of colorectal cancer micrometastasis in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20 J Surg Oncol 68 34–40

    Google Scholar 

  17. JE Hardingham PJ Hewett RE Sage et al. (2000) ArticleTitleMolecular detection of blood-borne epithelial cells in colorectal cancer patients and in patients with benign bowel disease Int J Cancer 89 8–13

    Google Scholar 

  18. LH Sobin C Wittekind (1997) NoChapterTitle International Union Against Cancer (UICC). TNM classification of malignant tumors EditionNumber5th ed Wiley-Liss New York

    Google Scholar 

  19. B Gusterson R Ott (1990) ArticleTitleOccult axillary lymph-node micrometastasis in breast cancer Lancet 336 434–5

    Google Scholar 

  20. InstitutionalAuthorNameInternational (Ludwig) Breast Cancer Study Group (1990) ArticleTitlePrognostic importance of occult axillary lymph node micrometastases from breast cancers Lancet 335 1565–8

    Google Scholar 

  21. DM Goldenberg RM Sharkey FJ Primus (1978) ArticleTitleImmunocytochemical detection of carcinoembryonic antigen in conventional histopathology specimens Cancer 42 1546–53

    Google Scholar 

  22. N Hayashi I Ito A Yanagisawa et al. (1995) ArticleTitleGenetic diagnosis of lymph-node metastasis in colorectal cancer Lancet 345 1257–9

    Google Scholar 

  23. JA Brennan L Mao RH Hruban et al. (1995) ArticleTitleMolecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck N Engl J Med 332 429–35

    Google Scholar 

  24. JE Hardingham WJ Butler D Roder et al. (1998) ArticleTitleSomatic mutations, acetylator status, and prognosis in colorectal cancer Gut 42 669–72

    Google Scholar 

  25. JE Hardingham D Kotasek RE Sage MC Eaton VH Pascoe A Dobrovic (1995) ArticleTitleDetection of circulating tumor cells in colorectal cancer by immunobead-PCR is a sensitive prognostic marker for relapse of disease Mol Med 1 789–94

    Google Scholar 

  26. Bustin SA, Dorudi S (1998) Molecular assessment of tumor stage and disease recurrence using PCR-based assays. Mol Med Today 4: 389-96.

    Google Scholar 

  27. SL Carrithers MT Barber SJ Parkinson et al. (1996) ArticleTitleGuanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues Proc Natl Acad Sci U S A 93 14827–32

    Google Scholar 

  28. B Cagir A Gelmann J Park et al. (1999) ArticleTitleGuanylyl cyclase C messenger RNA is a biomarker for recurrent stage II colorectal cancer Ann Intern Med 131 805–12

    Google Scholar 

  29. SA Waldman B Cagir J Rakinic et al. (1998) ArticleTitleUse of guanylyl cyclase C for detecting micrometastases in lymph nodes of patients with colon cancer Dis Colon Rectum 41 310–5

    Google Scholar 

  30. Y Miyake H Yamamoto Y Fujiwara et al. (2001) ArticleTitleExtensive micrometastases to lymph nodes as a marker for rapid recurrence of colorectal cancer: a study of lymphatic mapping Clin Cancer Res 7 1350–7

    Google Scholar 

  31. H Isozaki K Okajima K Fujii (1997) ArticleTitleHistological evaluation of lymph node metastasis on serial sectioning in gastric cancer with radical lymphadenectomy Hepatogastroenterology 44 1133–6

    Google Scholar 

  32. J Weitz P Kienle A Magener et al. (1999) ArticleTitleDetection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow Clin Cancer Res 5 1830–6

    Google Scholar 

  33. AE Merrie J Gunn LV Phillips et al. (1998) ArticleTitleThe anatomical distribution of colorectal cancer lymph node micrometastases (meeting abstract) ANZ J Surg 68 A135

    Google Scholar 

  34. JH Wong JB Bowles R Bueno D Shimizu (2002) ArticleTitleImpact of the number of negative nodes on disease-free survival in colorectal cancer patients Dis Colon Rectum 45 1341–8

    Google Scholar 

  35. M Prandi R Leonetto A Bini et al. (2002) ArticleTitlePrognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy Ann Surg 235 458–63

    Google Scholar 

  36. RC Newland OF Dent MN Lyttle PH Chapuis EL Bokey (1994) ArticleTitlePathological determinants of survival associated with colorectal cancer with lymph node metastases Cancer 73 2076–82

    Google Scholar 

  37. B Malassagne P Valleur J Serra et al. (1993) ArticleTitleRelationship of apical lymph node involvement to survival in resected colon carcinoma Dis Colon Rectum 36 645–53

    Google Scholar 

  38. PJ Bostick S Chatterjee DD Chi et al. (1998) ArticleTitleLimitations of specific RT-PCR markers in the detection of metastases in the lymph nodes and blood of breast cancer patients J Clin Oncol 16 2631–40

    Google Scholar 

  39. AE Merrie AM Rij Particlevan ER Dennett LV Phillips K Yun JL McCall (2003) ArticleTitlePrognostic significance of occult metastases in colon cancer Dis Colon Rectum 46 221–31

    Google Scholar 

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ACKNOWLEDGMENTS

The authors thank the Department of Surgery, in particular Mr. D. Rodda and Mr. S. Chew, and the Department of Histopathology, for their cooperation.

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Correspondence to Jennifer E. Hardingham Ph.D..

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This work was supported by grants from the Cancer and Bowel Research Trust and the Cancer Council of South Australia.

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Chen, G., McIver, C., Texler, M. et al. Detection of Occult Metastasis in Lymph Nodes From Colorectal Cancer Patients: A Multiple-Marker Reverse Transcriptase-Polymerase Chain Reaction Study. Dis Colon Rectum 47, 679–686 (2004). https://doi.org/10.1007/s10350-003-0118-2

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  • DOI: https://doi.org/10.1007/s10350-003-0118-2

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