Response: Re: Clonal Expansion and Loss of Heterozygosity at Chromosomes 9p and 17p in Premalignant Esophageal (Barrett's) Tissue

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We appreciate the comments of Walch et al. concerning the differences between our respective studies. Both groups used objective methods (comparative genomic hybridization [CGH] versus fluorescent loss of heterozygosity analysis) to assess somatic genetic abnormalities in Barrett's esophagus. Both groups provided similar data that progression is associated with nonlinear evolution of neoplastic cell lineages leading to clonal heterogeneity in Barrett's epithelium.

Walch et al. applied “exclusively morphologically linked techniques” to correlate their findings to specific histologic grades. However, routine histologic interpretation of dysplasia in Barrett's esophagus is subjective, and numerous studies have found that the results are not generally reproducible. For example, in our study of observer variation, there was only 48% agreement on all grades of a dysplasia classification system, and another study reported 63% agreement (1,2). Objective, reproducible methods are essential for independent validation of results by other investigators. We and others (3,4) have prospectively validated objective flow cytometric biomarkers that have high interlaboratory reproducibility. Furthermore, flow sorting purifies neoplastic clones that can arise independent of morphologic changes (5). It is unlikely that clonal heterogeneity can be attributed simply to histologic heterogeneity because extensive clonal heterogeneity has been documented independent of histologic findings (5), which is consistent with the observations of Walch et al. that the same histologic grade can have multiple, different chromosomal abnormalities in different patients.