光动力治疗后隐匿的巴雷特食管上皮显示隐窝增殖减少且无DNA含量异常。

Buried Barrett's epithelium following photodynamic therapy shows reduced crypt proliferation and absence of DNA content abnormalities.

作者信息

Hornick Jason L, Mino-Kenudson Mari, Lauwers Gregory Y, Liu Weitian, Goyal Raj, Odze Robert D

机构信息

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

出版信息

Am J Gastroenterol. 2008 Jan;103(1):38-47. doi: 10.1111/j.1572-0241.2007.01560.x. Epub 2007 Dec 11.

DOI:10.1111/j.1572-0241.2007.01560.x

PMID:18076737

Abstract

OBJECTIVES

Photodynamic therapy (PDT) is increasingly used for the treatment of patients with Barrett's esophagus (BE) with dysplasia or early carcinoma. Post-PDT, some patients show residual BE either exposed to the luminal surface (nonburied) or buried underneath reepithelialized squamous mucosa (buried BE). Buried BE may be a serious clinical problem since it can go unnoticed during surveillance endoscopies. The neoplastic potential of buried BE is poorly understood. The aim of this study was to evaluate the biological characteristics of nonburied and buried BE in patients treated with PDT.

METHODS

Twelve patients selected from a cohort of 52 BE patients who received PDT for high-grade dysplasia or intramucosal adenocarcinoma were used for this study because they all had both pre- and post-PDT (nonburied), and post-PDT buried, BE biopsies, without dysplasia, available for analysis. The biopsies were immunostained for Ki-67, p53, cyclin D1, bcl-2, TGF-alpha, EGFR, and AMACR. High fidelity DNA histograms were obtained by image cytometry analysis of Feulgen stained slides, and used to determine peak DNA index (DI), DNA heterogeneity, and 5N exceeding rate (5NER). Comparisons were made between pre-PDT nonburied BE and post-PDT nonburied and buried BE.

RESULTS

Pre-PDT BE showed an elevated Ki-67 crypt proliferation rate (43.3%) and p53, bcl-2, TGF-alpha, and EGFR positivity in 8%, 25%, 75%, and 25% of cases, respectively. Cyclin D1 and AMACR were negative in all cases. High fidelity DNA histograms showed mild aneuploidy in 73% of cases. Post-PDT buried BE showed a significantly lower Ki-67 crypt proliferation rate (29.9%) in comparison to nonburied BE, in both pre- PDT (43.3%) and post-PDT (44.4%) biopsies (P < 0.05), but similar rates of positivity for the other peptide markers. In contrast to pre-PDT nonburied BE biopsies, high fidelity DNA histograms revealed that none of the buried BE (0%), and only 2/9 (11%) nonburied BE post-PDT, showed aneuploidy.

CONCLUSIONS

Pre-PDT nonburied BE, without dysplasia, shows elevated crypt proliferation and mild, but frequent, DNA content abnormalities. Post-PDT, nonburied BE shows persistently elevated crypt proliferation, but significantly less frequent DNA content abnormalities, whereas buried BE shows decreased crypt proliferation and normal DNA content profile. These results suggest that post-PDT buried BE may have a lower neoplastic potential than pre-PDT BE.

摘要

目的

光动力疗法（PDT）越来越多地用于治疗伴有发育异常或早期癌的巴雷特食管（BE）患者。PDT治疗后，一些患者显示残留的BE，要么暴露于管腔表面（非埋藏型），要么埋藏于再上皮化的鳞状黏膜下方（埋藏型BE）。埋藏型BE可能是一个严重的临床问题，因为在监测内镜检查期间可能未被发现。埋藏型BE的肿瘤发生潜能了解甚少。本研究的目的是评估接受PDT治疗患者中，非埋藏型和埋藏型BE的生物学特性。

方法

从52例因高级别发育异常或黏膜内腺癌接受PDT治疗的BE患者队列中选取12例患者进行本研究，因为他们均有PDT治疗前（非埋藏型）、PDT治疗后（非埋藏型）以及PDT治疗后埋藏型BE的活检标本，且无发育异常，可供分析。对活检标本进行Ki-67、p53、细胞周期蛋白D1、bcl-2、转化生长因子-α（TGF-α）、表皮生长因子受体（EGFR）和α-甲基酰基辅酶A消旋酶（AMACR）免疫染色。通过对福尔根染色玻片进行图像细胞术分析获得高保真DNA直方图，用于确定峰值DNA指数（DI）、DNA异质性和5倍体超标率（5NER）。对PDT治疗前非埋藏型BE与PDT治疗后非埋藏型和埋藏型BE进行比较。

结果

PDT治疗前BE显示Ki-67隐窝增殖率升高（43.3%），p53、bcl-2、TGF-α和EGFR阳性率分别为8%、25%、75%和25%。细胞周期蛋白D1和AMACR在所有病例中均为阴性。高保真DNA直方图显示73%的病例有轻度非整倍体。与非埋藏型BE相比，PDT治疗后埋藏型BE的Ki-67隐窝增殖率显著降低（29.9%），在PDT治疗前（43.3%）和PDT治疗后（44.4%）的活检标本中均如此（P<0.05），但其他肽标志物的阳性率相似。与PDT治疗前非埋藏型BE活检标本不同，高保真DNA直方图显示，埋藏型BE无一例（0%）出现非整倍体，而PDT治疗后非埋藏型BE仅2/9（11%）出现非整倍体。