DNA flow cytometric analysis of paraffin-embedded tissue for the diagnosis of malignancy in bile duct biopsies.

DNA flow cytometric analysis of paraffin-embedded tissue for the diagnosis of malignancy in bile duct biopsies.
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DOI:
10.1016/j.humpath.2020.04.002
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发表时间:
2020-05
期刊:
影响因子:
3.3
通讯作者:
Choi WT
Choi WT
中科院分区:
医学3区
文献类型:
--
作者:
Lee H;Rabinovitch PS;Mattis AN;Kakar S;Choi WT

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在胆管活检中,区分反应性与肿瘤性上皮变化可能具有挑战性。样本通常很少,扭曲,并与明显的炎症,溃疡和/或碎片混合。恶性肿瘤的组织学确认通常需要在开始手术治疗之前,恶性肿瘤的错误诊断可能导致不必要的临床治疗。通过DNA流式细胞术对63例胆管活检的福尔马林固定石蜡包埋(FFPE)组织进行非整倍体评估:10例诊断为恶性(7例腺癌和3例至少高度异型增生[HGD]); 3例非典型诊断显示罕见的非典型腺体/细胞,涉及但不确定恶性肿瘤; 28例可能为反应性活检,伴有急性/慢性炎症、溃疡和/或轻度核性膀胱炎; 22例其他良性活检,无显著炎症、溃疡或核性膀胱炎。非整倍体检出率为70%(7/10例腺癌和2/3例至少HGD),所有3例(100%)非典型活检,50例良性活检中无一例。所有3例非整倍体的非典型病例随后被发现患有腺癌(n = 2)或HGD(n = 1)。在2例至少HGD伴非整倍体的病例中,1例发展为腺癌,但另1例无随访信息。其余1例至少为HGD的病例,尽管DNA含量正常,但在随访时发现患有腺癌。在平均37个月(范围:0-282个月)的随访时间内,50例良性病例(进一步得到正常DNA含量的支持)均未发展为腺癌。非整倍体作为恶性肿瘤(腺癌和HGD)诊断标志物的估计灵敏度为70%,特异性为100%,阳性预测值为100%,阴性预测值为94%。总之,使用胆管活检组织的FFPE进行DNA流式细胞术显示恶性病例的非整倍体率较高(70%),而所有良性活检组织的DNA含量正常。尽管样本量较小,但结果表明,该测定法可能适用于挑战性非典型病例,其中形态学评价受到非典型腺体/细胞、炎症和/或溃疡缺乏的限制。
Differentiation of reactive versus neoplastic epithelial changes can be challenging in bile duct biopsies. The samples are often scant, distorted, and mixed with significant inflammation, ulceration, and/or debris. Histological confirmation of malignancy is often required before the initiation of surgical therapy, and an erroneous diagnosis of malignancy can lead to unnecessary clinical management. Aneuploidy assessment by DNA flow cytometry was performed on formalin-fixed paraffin-embedded (FFPE) tissue from 63 bile duct biopsies: 10 with a malignant diagnosis (7 with adenocarcinoma and 3 with at least high-grade dysplasia [HGD]); 3 with an atypical diagnosis showing rare atypical glands/cells, concerning but not definite for malignancy; 28 likely reactive biopsies with acute/chronic inflammation, ulceration, and/or mild nuclear atypia; and 22 additional benign biopsies without significant inflammation, ulceration, or nuclear atypia. Aneuploidy was detected in 7 (70%) of the 10 biopsies with definite neoplasia (5 of 7 adenocarcinoma cases and 2 of 3 at least HGD cases), all 3 (100%) atypical biopsies, and none of the 50 benign biopsies. All 3 atypical cases with aneuploidy were subsequently found to have adenocarcinoma (n = 2) or HGD (n = 1). Among the 2 cases of at least HGD with aneuploidy, 1 case developed adenocarcinoma, but no follow-up information was available in the other case. The remaining 1 case of at least HGD, despite having normal DNA content, was found to have adenocarcinoma on follow-up. None of the 50 benign cases (further supported by normal DNA content) developed adenocarcinoma within a mean follow-up time of 37 months (range: 0–282 months). The estimated sensitivity of aneuploidy as a diagnostic marker of malignancy (adenocarcinoma and HGD) was 70%, with the specificity of 100%, positive predictive value of 100%, and negative predictive value of 94%. In conclusion, DNA flow cytometry using FFPE tissue from bile duct biopsies demonstrates a high rate of aneuploidy (70%) in malignant cases and normal DNA content in all benign biopsies. Although the sample size is small, the results indicate that this assay can be potentially useful in challenging atypical cases, where morphological evaluation is limited by scarcity of atypical glands/cells, inflammation, and/or ulceration.
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