Aberrant p53 Expression in Gastric Biopsies and Resection Specimens Following Neoadjuvant Chemoradiation: A Diagnostic Pitfall.

Aberrant p53 Expression in Gastric Biopsies and Resection Specimens Following Neoadjuvant Chemoradiation: A Diagnostic Pitfall.
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DOI:
10.1177/10668969231157304
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发表时间:
2023-12
影响因子:
1.2
通讯作者:
Montgomery, Elizabeth A.
Montgomery, Elizabeth A.
中科院分区:
医学4区
文献类型:
--
作者:
Hutchings, Danielle A.;Salimian, Kevan J.;Waters, Kevin M.;Birkness-Gartman, Jacqueline E.;Voltaggio, Lysandra;Assarzadegan, Naziheh;Huang, Jialing L.;Lin, Ming-Tseh;Singhi, Aatur D.;Montgomery, Elizabeth A.

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接受新辅助放射治疗和/或化疗的患者的胃粘膜活检和切除是常见的。这些标本可能显示出与治疗相关的组织学特征,包括炎症、溃疡和上皮异型性。在某些情况下,上皮异型性可能明显,促使使用辅助的P53免疫组织化学。用免疫组织化学方法检测治疗后胃粘膜组织中P53蛋白的表达。我们对60例胃食道癌(n=33)和胰腺癌(n=27)患者的57例胃切除和3例粘膜活检标本进行了组织学和P53免疫组织化学检测。我们确定了60例中的50例(83%)与治疗相关的上皮改变的组织形态特征。近半数病例(27/60例;45%)至少有局灶性P53表达异常,所有病例均显示治疗相关的上皮细胞改变的形态证据。神经内分泌细胞微核率62%(37/60)。下一代测序(NGS)的病灶治疗相关的上皮变化,显示异常的P53表达和癌症来自同一患者尝试,并在1名患者的结果。有趣的是,在患者的腺癌和组织学上良性的食道粘膜下腺中发现了不同的TP53改变,并发现了与治疗相关的上皮改变和异常的P53表达。我们的结果表明,在放疗和/或化疗后的胃粘膜标本中,P53的异常表达相对常见,提示在区分与治疗相关的变化与异型增生或癌时,应避免P53的表达。此外,我们的NGS结果提出了有趣的生物学问题,这可能值得进一步研究。
Gastric mucosal biopsies and resections from patients treated with neoadjuvant radiation and/or chemotherapy are frequently encountered. These samples may show histologic features related to therapy including inflammation, ulceration, and epithelial atypia. In some cases, epithelial atypia may be marked, prompting the use of adjunct p53 immunohistochemistry. We examined p53 expression by immunohistochemistry in gastric mucosa following therapy. We evaluated the histology and p53 immunohistochemical expression in gastric mucosa from 57 resections and 3 mucosal biopsies, from 60 patients treated with radiation and/or chemotherapy for gastroesophageal carcinoma (n = 33) or pancreatic carcinoma (n = 27). We identified histomorphologic features of therapy-related epithelial changes in 50 of 60 cases (83%). Abnormal p53 expression was present at least focally in nearly half the cases (27 of 60 cases; 45%), all of which showed morphologic evidence of therapy-related epithelial changes. Neuroendocrine cell micronests were present in 37 of 60 cases (62%). Next-generation sequencing (NGS) of foci with therapy-related epithelial changes showing abnormal p53 expression and carcinoma from the same patient was attempted and yielded results in 1 patient. Interestingly, differing TP53 alterations in the patient’s adenocarcinoma and in a histologically benign esophageal submucosal gland with therapy-related epithelial changes and abnormal p53 expression were identified. Our results demonstrate that abnormal p53 expression is relatively common in gastric mucosal samples following radiation and/or chemotherapy and suggest that p53 expression should be avoided when distinguishing therapy-related changes from dysplasia or carcinoma. Furthermore, our NGS results raise interesting biological questions, which may warrant further investigation.
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