Original Communications| Volume 129, ISSUE 6, P684-691, June 2001

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Skip metastases in colon cancer: Assessment by lymph node mapping using molecular detection


      Background. Colon cancer has been assumed to spread sequentially through the regional lymphatic bed, with skip metastases occurring in only 1% to 3% of cases. Molecular techniques allow the detection of occult metastases, but to date have not been applied to assess the pattern of regional lymphatic spread of colon cancer. Methods. Fifty-five tumors from 54 patients with colonic adenocarcinoma were studied. Lymph node mapping was performed on fresh colonic specimens recording the position of each node on an anatomical diagram. Half of each lymph node was submitted for routine histology examination and half assayed for keratin 20 gene expression by reverse transcription-polymerase chain reaction. Logistic regression was used to analyze the distribution of histologic and occult metastases. Results. A total of 1084 lymph nodes were dissected (median, 19 nodes; range, 4-52). Sixty-four lymph nodes from 20 tumors had histologically evident metastases and 76 lymph nodes from 13 tumors had occult metastases. There was no difference in the distribution of either histologic or occult metastases among paracolic, intermediate, and apical node groups. Ten patients had evidence of anatomical skip lesions after lymph node mapping and molecular analysis, only 1 of which was histologically detectable. Conclusions. This study demonstrates a higher incidence of skip metastases in colon cancer assessed by molecular techniques than has previously been reported, challenging the concept of sequential development of early lymph node metastases.(Surgery 2001;129:684-91.)
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        • Finlay I
        • McArdle C.
        The identification of patients at high risk following curative resection for colorectal carcinoma.
        Br J Surg. 1982; 69: 583-584
        • Newland RC
        • Chapuis PH
        • Smyth EJ
        The prognostic value of substaging colorectal carcinoma. A prospective study of 1117 cases with standardized pathology.
        Cancer. 1987; 60: 852-857
        • Newland RC
        • Dent OF
        • Lyttle MN
        • et al.
        Pathologic determinants of survival associated with colorectal cancer with lymph node metastases. A multivariate analysis of 579 patients.
        Cancer. 1994; 73: 2076-2082
        • Merrie AEH
        • Yun K
        • van Rij AM
        • et al.
        Detection and significance of minimal residual disease in colorectal cancer.
        Histol Histopathol. 1999; 14: 561-569
        • Phillips RK
        • Hittinger R
        • Blesovsky L
        • et al.
        Large bowel cancer: surgical pathology and its relationship to survival.
        Br J Surg. 1984; 71: 604-610
        • Fielding LP
        • Phillips RK
        • Fry JS
        • et al.
        Prediction of outcome after curative resection for large bowel cancer.
        Lancet. 1986; 2: 904-907
        • Wolmark N
        • Fisher B
        • Wieand HS
        The prognostic value of the modifications of the Dukes' C class of colorectal cancer. An analysis of the NSABP clinical trials.
        Ann Surg. 1986; 203: 115-122
        • Hyder JW
        • Talbott TM
        • Maycroft TC
        A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982.
        Dis Colon Rectum. 1990; 33: 923-925
        • Cohen AM
        • Tremiterra S
        • Candela F
        • et al.
        Prognosis of node-positive colon cancer.
        Cancer. 1991; 67: 1859-1861
        • Haboubi NY
        • Clark P
        • Kaftan SM
        • et al.
        The importance of combining xylene clearance and immunohistochemistry in the accurate staging of colorectal carcinoma.
        J Royal Soc Med. 1992; 85: 386-388
        • Nicholson AG
        • Marks CG
        • Cook MG
        Effect on lymph node status of triple levelling and immunohistochemistry with CAM 5.2 on node negative colorectal carcinomas.
        Gut. 1994; 35: 1447-1448
        • Hitchcock CL
        • Sampsel J
        • Young DC
        • et al.
        Limitations with light microscopy in the detection of colorectal cancer cells.
        Dis Colon Rectum. 1999; 42: 1046-1052
        • Schlimok G
        • Funke I
        • Bock B
        • et al.
        Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance.
        J Clin Oncol. 1990; 8: 831-837
        • Lindemann F
        • Schlimok G
        • Dirschedl P
        • et al.
        Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients.
        Lancet. 1992; 340: 685-689
        • Greenson JK
        • Isenhart CE
        • Rice R
        • et al.
        Identification 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. 1994; 73: 563-569
        • Hayashi N
        • Ito I
        • Yanagisawa A
        • et al.
        Genetic diagnosis of lymph-node metastasis in colorectal cancer.
        Lancet. 1995; 345: 1257-1259
        • Liefers GJ
        • Cleton-Jansen AM
        • van de Velde CJH
        • et al.
        Micrometastases and survival in stage II colorectal cancer.
        N Engl J Med. 1998; 339: 223-228
        • Gunn J
        • McCall JL
        • Yun K
        • et al.
        Detection of micrometastases in colorectal cancer patients by K19 and K20 reverse-transcription polymerase chain reaction.
        Lab Invest. 1996; 75: 611-616
        • Dorudi S
        • Kinrade E
        • Marshall NC
        • et al.
        Genetic detection of lymph node micrometastases in patients with colorectal cancer.
        Br J Surg. 1998; 85: 98-100
        • Weitz J
        • Kienle P
        • Magener A
        • et al.
        Detection of disseminated colorectal cancer cells in lymph nodes, blood, and bone marrow.
        Clin Cancer Res. 1999; 5: 1830-1836
        • DiDomenico N
        • Link L
        • Knobel R
        • et al.
        COBAS AMPLICOR: fully automated RNA and DNA amplification and detection system for routine diagnostic PCR.
        Clin Chem. 1996; 42: 1915-1923
        • McMinn RMH
        Last's anatomy, regional and applied.
        Churchill Livingstone, Melbourne1994
        • Dukes C.
        The classification of cancer of the rectum.
        J Pathol Bacteriol. 1932; 35: 323-332
        • Gabriel W
        • Dukes C
        • Bussey H.
        Lymphatic spread in cancer of the rectum.
        Br J Surg. 1935; 23: 395-413
        • Herrera-Ornelas L
        • Justiniano J
        • Castillo N
        • et al.
        Metastases in small lymph nodes from colon cancer.
        Arch Surg. 1987; 122: 1253-1256
        • Tang R
        • Wang JY
        • Chen JS
        • et al.
        Survival impact of lymph node metastasis in TNM stage III carcinoma of the colon and rectum.
        J Am Coll Surg. 1995; 180: 705-712
        • Moll R
        • Franke WW
        • Schiller DL
        • et al.
        The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors, and cultured cells.
        Cell. 1982; 31: 11-24
        • Moll R
        • Lowe A
        • Laufer J
        • et al.
        Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies.
        Am J Pathol. 1992; 140: 427-447
        • Moll R
        • Zimbelmann R
        • Goldschmidt MD
        • et al.
        The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas.
        Differentiation. 1993; 53: 75-93
        • Adams MD
        • Kerlavage AR
        • Fleischmann RD
        • et al.
        Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence.
        Nature. 1995; 377: 3-174
        • Burchill SA
        • Bradbury MF
        • Pittman K
        • et al.
        Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.
        Br J Cancer. 1995; 71: 278-281
        • Futamura M
        • Takagi Y
        • Koumura H
        • et al.
        Spread of colorectal cancer micrometastases in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20.
        J Surg Oncol. 1998; 68: 34-40
        • Yun K
        • Merrie AEH
        • Gunn J
        • et al.
        Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-ras mutations.
        J Pathol. 2000; 191: 21-26
      1. General rules for clinical and pathological studies on cancer of the colon, rectum and anus. Japanese Research Society for Cancer of the Colon Rectum and Anus. Kanahera, Tokyo1994: 14-25
        • Merrie AEH
        • Phillips LV
        • Yun K
        • et al.
        Skip lesions in colon cancer: assessment by lymph node mapping.
        Eur J Nucl Med. 1999; 26: S73
        • Uren RF
        • Howman-Giles R
        • Thompson JF
        • et al.
        Lymphoscintigraphy to identify sentinel lymph nodes in patients with melanoma.
        Melanoma Res. 1994; 4: 395-399
        • Uren RF
        • Howman-Giles R
        • Thompson JF
        Lymphatic drainage from the skin of the back to retroperitoneal and paravertebral lymph nodes in melanoma patients.
        Ann Surg Oncol. 1998; 5: 384-387
        • Pezim ME
        • Nicholls RJ
        Survival after high or low ligation of the inferior mesenteric artery during curative surgery for rectal cancer.
        Ann Surg. 1984; 200: 729-733
        • Surtees P
        • Ritchie JK
        • Phillips RK
        High versus low ligation of the inferior mesenteric artery in rectal cancer.
        Br J Surg. 1990; 77: 618-621
        • Corder AP
        • Karanjia ND
        • Williams JD
        • et al.
        Flush aortic tie versus selective preservation of the ascending left colic artery in low anterior resection for rectal carcinoma.
        Br J Surg. 1992; 79: 680-682