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Walch, A.K. ; Zitzelsberger, H. ; Bink, K.* ; Hutzler, P. ; Bruch, J. ; Braselmann, H. ; Aubele, M. ; Müller, J.* ; Stein, H.* ; Siewert, J.R.* ; Höfler, H. ; Werner, M.*

Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: Comparison with nonmetastatic Barrett's adenocarcinoma.

Mod. Pathol. 13, 814-824 (2000)
Verlagsversion Volltext DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Lymph node metastasis is one of the strongest negative prognostic factors for patients with Barrett's adenocarcinoma (BCA). However, despite the importance of the metastatic process in BCA, the molecular basis of it remains poorly understood. To search for cytogenetic events associated with metastasis in regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their lymph node metastases and compared them with 18 nonmetastatic BCA. In metastatic primary BCA, we observed significantly more DNA gains on 3q (P = .013), 17q (P = .019), and 22q (P = .021) compared with nonmetastatic primary BCA. No statistically significant correlation could be observed between DNA copy number changes and the histopathologic stage, grade, or survival (P > .05). The most frequent alteration observed only in lymph node metastases but not in the related primary tumor was loss of 2q (5 of 8). Coamplification of 7p and chromosome 17 was found in 6 of 8 lymph node metastases. A comparison of DNA copy number changes between primary tumors and their corresponding metastases indicated a high degree of genetic heterogeneity. Fluorescence in situ hybridization analysis demonstrated the involvement of the Her-2/neu gene in primary BCA and its related lymph node metastases. Each of the investigated primary tumors and related lymph node metastases also showed striking heterogeneity with respect to Her-2/neu, with several areas displaying different levels of amplification. In summary, our data indicate that DNA copy number changes on 2q, 3q, 7p, 17q, and 22q may be involved in the metastatic process in BCA. Furthermore, the striking genetic heterogeneity that we found between primary BCA and its lymph node metastases may underlie BCA's poor responsiveness to therapy and could help explain why prognostic biomarkers measured exclusively in primary tumors give an incomplete view of the biologic potential of BCA.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Barrett's adenocarcinoma; comparative genomic hybridization; fluorescence in situ hybridization; genetic heterogeneity; metastasis; COMPARATIVE GENOMIC HYBRIDIZATION; DYSPLASIA-CARCINOMA SEQUENCE; ESOPHAGEAL ADENOCARCINOMAS; GASTROESOPHAGEAL JUNCTION; CHROMOSOMAL IMBALANCES; LASER-MICRODISSECTION; GASTRIC CARCINOMAS; BREAST-CANCER; AMPLIFICATION; CLONING
ISSN (print) / ISBN 0893-3952
e-ISSN 1530-0285
Zeitschrift Modern Pathology
Quellenangaben Band: 13, Heft: 7, Seiten: 814-824 Artikelnummer: , Supplement: ,
Verlag United States and Canadian Academy of Pathology ; Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
Institute of Molecular Radiation Biology (IMS)