Reid B J, Blount P L, Rubin C E, Levine D S, Haggitt R C, Rabinovitch P S
Department of Medicine, University of Washington, Seattle.
Gastroenterology. 1992 Apr;102(4 Pt 1):1212-9.
To determine whether or not flow-cytometric evidence of aneuploidy and increased G2/tetraploid fractions predispose to neoplastic progression in Barrett's esophagus, 62 patients with Barrett's esophagus were evaluated prospectively for a mean interval of 34 months. Nine of 13 patients who showed aneuploid or increased G2/tetraploid populations in their initial flow-cytometric analysis developed high-grade dysplasia or adenocarcinoma during follow-up; none of the 49 patients without these abnormalities progressed to high-grade dysplasia or cancer (P less than 0.0001). Neoplastic progression was characterized by progressive flow-cytometric and histological abnormalities. Patients who progressed to high-grade dysplasia and carcinoma frequently developed multiple aneuploid populations of cells that were detectable flow-cytometrically. Similarly, patients appeared to progress through a phenotypic sequence that could be recognized histologically by the successive appearance of Barrett's metaplasia negative for dysplasia, abnormalities in the indefinite/low-grade dysplasia range, high-grade dysplasia, and eventually adenocarcinoma. These and prior results suggest that neoplastic progression in Barrett's esophagus occurs in a subset of patients who have an acquired genomic instability that generates abnormal clones of cells, some of which have aneuploid or increased G2/tetraploid DNA contents. With continued genomic instability, multiple aneuploid subclones may evolve, one of which may ultimately acquire the ability to invade and become an early carcinoma. The combination of histology and flow cytometry can be used to identify a subset of patients with Barrett's esophagus who merit more frequent endoscopic surveillance for the early detection of high-grade dysplasia or carcinoma.
为了确定非整倍体的流式细胞术证据以及G2/四倍体比例增加是否易导致巴雷特食管发生肿瘤进展，对62例巴雷特食管患者进行了前瞻性评估，平均随访间隔为34个月。在初始流式细胞术分析中显示非整倍体或G2/四倍体群体增加的13例患者中，有9例在随访期间发展为高级别异型增生或腺癌；49例无这些异常的患者均未进展为高级别异型增生或癌症（P<0.0001）。肿瘤进展的特征是流式细胞术和组织学异常逐渐加重。进展为高级别异型增生和癌的患者经常出现多个可通过流式细胞术检测到的非整倍体细胞群体。同样，患者似乎经历了一个表型序列，通过巴雷特化生对异型增生呈阴性、不确定/低级别异型增生范围内的异常、高级别异型增生以及最终腺癌的相继出现，在组织学上可以识别。这些结果和先前的结果表明，巴雷特食管的肿瘤进展发生在一部分具有获得性基因组不稳定的患者中，这种不稳定会产生异常细胞克隆，其中一些细胞具有非整倍体或增加的G2/四倍体DNA含量。随着基因组不稳定的持续，多个非整倍体亚克隆可能会演变，其中一个最终可能获得侵袭能力并成为早期癌。组织学和流式细胞术的结合可用于识别一部分巴雷特食管患者，他们需要更频繁的内镜监测以早期发现高级别异型增生或癌。
