Central Mesenteric Lymph Node BER-Ep4+ Cells in Colorectal Cancer: Challenge to Sentinel Node Concept?

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Abstract

Background: The role of sentinel lymph nodes in colorectal cancer remains unclear. Methods: Cryosections from central para-aortic mesenterial lymph nodes were stained using mAb BER-Ep4. Overall survival and distant recurrence were calculated using Kaplan-Meier plots. Results: All patients (n = 48) were free of distant metastases and curatively resected (R0). 23 pN0, 13 pN1 and 12 pN2 stages were found. 21/48 patients (44%) showed BER-Ep4+ cells in their central lymph nodes (7/23 pN0, 8/13 pN1, 6/12 pN2). In 6/23 pN0 patients, BER-Ep4+ cells were also found in locoregional nodes (p = 0.03, Fisher’s exact test). pN status predicted overall survival (p = 0.006, Kaplan-Meier curve, log-rank test). An impact was exerted by central mesenteric BER-Ep4+ cells on overall survival (p = 0.009 in pN0 patients, p = 0.07 for all pN) and distant recurrence-free survival (p = 0.001 in pN0 patients, p = 0.007 for all pN). Multivariate analysis showed an independent prognostic effect on overall survival in pN0 patients (p = 0.022). Conclusion: Central lymph nodes are sentinels of disease not amenable to extended lymphadenectomy and might identify patients at risk of distant organ recurrence.

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Lymph node metastasis in T1 adenocarcinoma of the colon and rectum.

G Nash, José G Guillem, Martin R Weiser … (2004)

The biology of colorectal cancer differs according to location within the large intestine. To evaluate the clinical significance of tumor location as a risk factor for lymph node metastasis (LNM), we performed a detailed pathological review of T1 adenocarcinomas of the colon and rectum. T1 adenocarcinomas of the colon and rectum treated by radical resection (n=428) were identified from prospective clinical databases at two institutions. Tumor location was assigned as right colon (cecum to transverse), left colon (splenic flexure to sigmoid), or rectum (0-18 cm from AV). Pathology slides were reviewed, extent of submucosal invasion (sm width, sm depth) was quantified using an optical micrometer, and morphologic features of the cancer and its infiltrating margin were recorded. The overall rate of LNM was 10%. On univariate analysis, LNM was significantly more common in the rectum (27/176, 15%) compared to the left colon (13/160, 8%, p=.04) or right colon (3/92, 3%, p=.003). However, on multivariate analysis, deep submucosal invasion and lymphovascular invasion were independent and significant risk factors, whereas tumor location was not. T1 colorectal cancers have a progressively higher risk of LNM as their location becomes more distal. However, the increasing rate of LNM observed in cancers of the left colon and rectum is explained by a higher prevalence of high-risk pathologic features. In early colorectal cancers, tumor morphology is the strongest clinical predictor of metastatic behavior.

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Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer.

A Rehders, J. R. Izbicki, S. Hosch … (1997)

Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells. We studied 1308 lymph nodes from 68 patients with esophageal cancer without overt metastases who had undergone radical en bloc esophagectomy. A total of 399 lymph nodes obtained from 68 patients were found to be free of tumor by routine histopathological analysis and were studied further for isolated tumor cells by immunohistochemical analysis with the monoclonal anti-epithelial-cell antibody Ber-EP4. This antibody did not stain lymph nodes from 24 control patients without carcinoma. Of the 399 "tumor free" lymph nodes, 67 (17 percent), obtained from 42 of the 68 patients, contained Ber-EP4-positive tumor cells. Fifteen of 30 patients who were considered free of lymph-node metastases by histopathological analysis had such cells in their lymph nodes, and 5 of the 15 had small primary tumors. Ber-EP4-positive cells found in "tumor free" nodes were independently predictive of significantly reduced relapse-free survival (P=0.008) and overall survival (P=0.03). They predicted relapse both in patients without nodal metastases (P=0.01) and in those with regional lymph-node involvement (P=0.007). All 12 patients whose lymph nodes were negative on both histopathological and immunohistochemical analysis and who were available for follow-up survived without recurrence. The presence of micrometastatic tumor cells in bone marrow had no additional prognostic value. Immunohistochemical examination of lymph nodes may improve the pathological staging of esophageal cancer.

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Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial.

G Niedobitek, R Schwarting, U Latza … (1990)

A new monoclonal antibody, Ber-EP4, directed against a partially formol resistant epitope on the protein moiety of two 34 kilodalton and 39 kilodalton glycopolypeptides on human epithelial cells is described. Immunostaining of a wide range of normal and neoplastic human tissues and cell lines showed that all carcinomas and all non-neoplastic epithelial cells, except hepatocytes, parietal cells, and apical cell layers in squamous epithelia, homogeneously expressed Ber-EP4 antigen. As Ber-EP4 does not detect any normal or neoplastic non-epithelial cells, this antibody might prove valuable for the differentiation of the following (i) non-epithelial tumours from undifferentiated carcinomas; (ii) hepatocytes from bile duct cells in certain liver diseases; (iii) mesothelial cells from carcinoma cells in lung biopsy specimens; and (iv) reactive mesothelial cells from carcinoma cells in smears of serous effusions.

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Author and article information

Journal

Journal ID (publisher-id): DSU

Journal ID (nlm-ta): Dig Surg

Journal ID (doi): 10.1159/issn.0253-4886

Title: Digestive Surgery

Publisher: S. Karger AG

ISSN (Print): 0253-4886

ISSN (Electronic): 1421-9883

Publication date Subscription-year: 2007

Publication date (Print): April 2007

Publication date (Electronic): 16 March 2007

Volume: 24

Issue: 1

Pages: 19-27

Affiliations

^aDepartment of General, Visceral and Thoracic Surgery, and ^bInstitute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Article

Publisher ID: 100914 Other ID: Dig Surg 2007;24:19–27

DOI: 10.1159/000100914

PubMed ID: 17369677

SO-VID: be0a1fd2-d2f6-42f8-955e-de5c9edead41

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 12 July 2006

Date accepted : 02 October 2006

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Figures: 5, Tables: 4, References: 28, Pages: 9

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Central Mesenteric Lymph Node BER-Ep4+ Cells in Colorectal Cancer: Challenge to Sentinel Node Concept?

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Karger: Gastroenterology

Most cited references 21

Lymph node metastasis in T1 adenocarcinoma of the colon and rectum.

Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer.

Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial.

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