Liu Weitian, Hahn Hejin, Odze Robert D, Goyal Raj K
Pathology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Gastroenterol. 2009 Apr;104(4):816-24. doi: 10.1038/ajg.2009.85. Epub 2009 Mar 17.
The mucosa of patients with columnar-lined esophagus recognized on endoscopy usually shows epithelium with and without goblet cells. Columnar epithelium with goblet cells ("Barrett's esophagus") is generally believed to represent a premalignant lesion and has been shown to contain DNA abnormalities. However, the biological properties of non-goblet columnar epithelium remain unknown. The purpose of this study was to determine the DNA content properties of non-goblet epithelium in patients with metaplastic columnar epithelium of the esophagus.
Mucosal biopsies of the esophagus from 68 patients with columnar metaplasia of the esophagus (22 without goblet cells and 46 with goblet cells) and 19 patients with normal gastric mucosa (controls) were histologically evaluated for the density of goblet cells. The latter group was divided into low-density, high-density, and very high-density goblet cell subgroups. Tissue sections of non-goblet epithelium and goblet cell epithelium (where present) were evaluated by image cytometry, and high-fidelity DNA histograms were created to indicate the G0/G1 peak DNA index (DI), DNA content heterogeneity index (HI), and the percentage of cells with DNA exceeding 5N (5N-EC). G0/G1 peaks with DI>1.1 were considered aneuploid.
Normal gastric controls showed a mean peak DI of 1.02+/-0.03 and an HI of 11.6+/-0.7. None of the controls revealed aneuploidy or 5N-EC. Patients with metaplastic columnar epithelium with goblet cells showed a DI of 1.15+/-0.12, HI of 18.2+/-2.1, mild aneuploidy in 54% of the cases, and 5N-EC in 15% of the cases, all of which were significantly higher than in controls. Patients with metaplastic columnar epithelium without goblet cells showed DNA content results statistically similar to those of patients with metaplastic columnar epithelium with goblet cells, and also revealed significantly higher values compared with those of controls. Furthermore, there were no significant differences in any of the key DNA content abnormalities between non-goblet and goblet cell-containing epithelium in patients with metaplastic columnar epithelium with goblet cells, or between these two types of epithelium according to the density of goblet cells.
DNA content abnormalities occur with equal frequency and extent in metaplastic columnar epithelium of the esophagus without goblet cells compared with metaplastic columnar epithelium with goblet cells. These findings suggest that metaplastic non-goblet columnar epithelium of the esophagus may have neoplastic potential.
在内镜检查中发现的柱状上皮食管患者的黏膜通常显示有杯状细胞和无杯状细胞的上皮。含有杯状细胞的柱状上皮(“巴雷特食管”)通常被认为是一种癌前病变,并且已显示含有DNA异常。然而,非杯状柱状上皮的生物学特性仍然未知。本研究的目的是确定食管化生柱状上皮患者中非杯状上皮的DNA含量特性。
对68例食管柱状化生患者(22例无杯状细胞,46例有杯状细胞)和19例正常胃黏膜患者(对照组)的食管黏膜活检组织进行组织学评估,以确定杯状细胞的密度。后一组分为低密度、高密度和极高密度杯状细胞亚组。通过图像细胞术评估非杯状上皮和杯状细胞上皮(如有)的组织切片,并创建高保真DNA直方图以显示G0/G1峰DNA指数(DI)、DNA含量异质性指数(HI)以及DNA超过5N的细胞百分比(5N-EC)。DI>1.1的G0/G1峰被认为是非整倍体。
正常胃对照组的平均峰DI为1.02±0.03,HI为11.6±0.7。对照组均未发现非整倍体或5N-EC。含有杯状细胞的化生柱状上皮患者的DI为1.15±0.12,HI为18.2±2.1,54%的病例有轻度非整倍体,15%的病例有5N-EC,所有这些均显著高于对照组。无杯状细胞的化生柱状上皮患者的DNA含量结果在统计学上与含有杯状细胞的化生柱状上皮患者相似,并且与对照组相比也显示出显著更高的值。此外,在含有杯状细胞的化生柱状上皮患者中,非杯状上皮和含杯状细胞的上皮之间,或根据杯状细胞密度划分的这两种上皮类型之间,在任何关键的DNA含量异常方面均无显著差异。
与含有杯状细胞的化生柱状上皮相比,无杯状细胞的食管化生柱状上皮中DNA含量异常的发生频率和程度相同。这些发现表明食管化生非杯状柱状上皮可能具有肿瘤形成潜能。