Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence - PubMed (original) (raw)

. 2000 Feb;156(2):555-66.

doi: 10.1016/S0002-9440(10)64760-8.

H F Zitzelsberger, J Bruch, G Keller, D Angermeier, M M Aubele, J Mueller, H Stein, H Braselmann, J R Siewert, H Höfler, M Werner

Affiliations

Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence

A K Walch et al. Am J Pathol. 2000 Feb.

Abstract

To characterize cytogenetic alterations found in Barrett's adenocarcinoma (BA) and, more importantly, its premalignant stages, we studied chromosomal imbalances in various lesions in the histologically proposed metaplasia-dysplasia-carcinoma sequence using comparative genomic hybridization (CGH). Using 30 esophageal adenocarcinoma resection specimens, we were able to study 30 areas of Barrett's adenocarcinoma and 8 lymph node metastases (LN). In addition, we investigated 25 premalignant lesions adjacent to BA derived from a subset of 14 resection specimens including 11 areas of high grade dysplasia (HGD), 8 areas of low grade dysplasia (LGD), and 6 areas of intestinal metaplasia (IM), which were laser-microdissected and studied with CGH. To validate the CGH findings, fluorescence in situ hybridization analysis on 13 BA with probes specific for HER-2/neu and 20q13.2 were performed. The chromosomal alterations most often identified in BA were: gains on 8q (80%), 20q (60%), 2p, 7p and 10q (47% each), 6p (37%), 15q (33%) and 17q (30%). Losses were observed predominantly on the Y-chromosome (76%), 4q (50%), 5q and 9p (43% each), 18q (40%), 7q (33%) and 14q (30%). High-level amplifications were observed on 8q23-qter, 8p12-pter, 7p11-p14, 7q21-31, 17q11-q23. Recurrent chromosomal changes were also identified in metaplastic (gains on 8q, 6p, 10q, losses on 13q, Y, 9p) and dysplastic epithelium (gains on 8q, 20q, 2p, 10q, 15q, losses on Y, 5q, 9p, 13q, 18q). Novel amplified chromosomal regions on chromosomes 2p and 10q were detected in both Barrett's adenocarcinoma and premalignant lesions. An increase of the average number of detected chromosomal imbalances from IM (7.0 +/- 1.7), to LGD (10.8 +/- 2.2), HGD (13.4 +/- 1.1), BA (13.3 +/- 1.4), and LN (22 +/- 1.2) was seen. Although the detection of common chromosomal alterations in premalignant lesions and adjacent carcinomas suggest a process of clonal expansion, the occurrence of several chromosomal changes in an apparently random order relative to one another is striking evidence that clonal evolution is more complex than would be predicted by linear models. This is probably a reflection of the existence of many divergent neoplastic subpopulations and highlights one of the main problems associated with surveillance of Barrett's patients, namely sampling error.

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Figures

Figure 1.

Figure 1.

Summary of DNA copy number changes detected by CGH in 30 BA. Lines to the left and the right of the chromosomes indicate the regions lost and gained, respectively. Thick bars represent regions of high-level gain. Imbalances found on chromosome 1p and chromosome 19 were not scored, as detailed in Material and Methods.

Figure 2.

Figure 2.

Summary of DNA copy number changes detected by CGH in six metaplastic (… … … … … … .), eight low grade dysplastic ( – – – – – ), and 11 high grade dysplastic (———-) areas. Lines to the left and the right of the chromosomes indicate the regions lost and gained, respectively. Thick bars represent regions of high-level gain. Imbalances found on chromosome 1p and chromosome 19 were not scored, as detailed in Material and Methods.

Figure 3.

Figure 3.

Heterogeneity of Her-2/neu gene amplification in Barrett’s adenocarcinoma (case 15, BA). Dual-color FISH with Her-2/_neu_-specific probe (red signals) and chromosome 17 centromeric probe (green signals) counterstained with DAPI. Note tumor cells on the left BA areas with high-level Her-2/neu amplification (clusters), whereas tumor cells on the right site show no or low-level Her-2/neu amplification.

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