Buried Barrett's epithelium following photodynamic therapy shows reduced crypt proliferation and absence of DNA content abnormalities
Buried Barrett's epithelium following photodynamic therapy shows reduced crypt proliferation and absence of DNA content abnormalities
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DOI：
10.1111/j.1572-0241.2007.01560.x
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发表时间：
2008-01-01
影响因子：
9.8
通讯作者：
Odze, Robert D.
中科院分区：
文献类型：
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作者：
Hornick, Jason L.;Mino-Kenudson, Mari;Odze, Robert D.
目的：光动力疗法（PDT）越来越多地用于治疗患有Barrett食管（BE）的异型增生或早期癌患者。PDT后，一些患者显示残留BE暴露于管腔表面（非埋藏）或埋藏在上皮再生的鳞状粘膜下方（埋藏BE）。埋藏BE可能是一个严重的临床问题，因为它可能在监视内窥镜检查中被忽视。埋藏BE的肿瘤潜力知之甚少。本研究的目的是评估生物学特性的nonburied和掩埋BE在患者治疗PDT.METHODS：12例患者从一个队列的52 BE患者接受PDT的高度异型增生或粘膜内腺癌被用于本研究，因为他们都有前和后PDT（nonburied），PDT后掩埋，BE活检，无异型增生，可用于分析。对活检组织进行Ki-67、p53、细胞周期蛋白D1、bcl-2、TGF-α、EGFR和AMACR免疫染色。通过Feulgen染色切片的图像细胞术分析获得高保真的DNA直方图，并用于确定峰值DNA指数（DI）、DNA异质性和5 N超标率（5 NER）。结果：PDT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%。Cyclin D1和AMACR均为阴性。高保真DNA直方图显示轻度非整倍体的情况下，73%。在PDT前（43.3%）和PDT后（44.4%）活检中，PDT后掩埋BE显示出与非掩埋BE相比显著较低的Ki-67隐窝增殖率（29.9%）（P < 0.05），但其他肽标记物的阳性率相似。对比前PDT nonburied BE活检，高保真DNA直方图显示，没有埋葬BE（0%），只有2/9（11%）nonburied BE post-PDT，表现出异倍体。结论：前PDT nonburied BE，没有发育不良，表现出升高的隐窝增殖和轻度，但频繁，DNA含量异常。PDT后，非埋藏BE表现出持续升高的隐窝增殖，但显着较低频率的DNA含量异常，而埋藏BE表现出隐窝增殖减少和正常的DNA含量分布。这些结果表明，PDT后埋藏BE可能比PDT前BE具有更低的肿瘤形成潜力。
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.