Immunohistochemical panel for distinguishing esophageal adenocarcinoma from squamous cell carcinoma: a combination of p63, cytokeratin 5/6, MUC5AC, and anterior gradient homolog 2 allows optimal subtyping

Immunohistochemical panel for distinguishing esophageal adenocarcinoma from squamous cell carcinoma: a combination of p63, cytokeratin 5/6, MUC5AC, and anterior gradient homolog 2 allows optimal subtyping
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DOI:
10.1016/j.humpath.2012.03.019
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发表时间:
2012-11-01
期刊:
影响因子:
3.3
通讯作者:
Pai, Reetesh K.
Pai, Reetesh K.
中科院分区:
医学3区
文献类型:
--
作者:
DiMaio, Michael A.;Kwok, Shirley;Pai, Reetesh K.

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食管腺癌和鳞状细胞癌的鉴别通常基于形态学标准,在小活检中可能很困难。我们分析了食管癌中常用的免疫组化标记物(p63,细胞角蛋白5/6,细胞角蛋白7,CDX 2,MUC 2和MUC 5AC)和2种新标记物,前梯度同系物2和SOX 2,以建立区分这些肿瘤的最佳面板。对69例食管腺癌和41例食管鳞状细胞癌全切片的组织微阵列进行这些标记物的染色和半定量评分。使用形态学诊断作为金标准,计算单个标志物和选择组合的灵敏度和特异性。所有鳞状细胞癌均表达p63,其中41例中的38例在超过75%的肿瘤细胞中表现出反应性。41例鳞状细胞癌中有40例细胞角蛋白5/6表达,其中39例在75%以上的肿瘤细胞中表现出反应性。SOX 2表达存在于41例鳞状细胞癌中的35例中,但也存在于69例腺癌中的24例中,经常在腺癌中表现出广泛的反应性。前梯度同源物2对腺癌高度敏感,存在于69例病例中的68例中,但前梯度同源物2反应性也在41例鳞状细胞癌中的15例中被鉴定,通常在鳞状细胞癌中表现出局灶反应性。MUC 5AC表达几乎仅见于腺癌,仅单个鳞状细胞癌显示局灶性MUC 5AC染色。总的来说,p63和细胞角蛋白5/6的双重表达对鳞状细胞癌的特异性为99%,敏感性为98%。此外,在p63和细胞角蛋白5/6染色缺失或减弱的情况下,前梯度同源物2和MUC 5AC是有用的腺癌阳性标志物。(c)2012 Elsevier Inc. All rights reserved.
Distinguishing adenocarcinoma and squamous cell carcinoma of the esophagus is often based on morphological criteria and can be difficult in small biopsies. We analyzed commonly used immunohistochemical markers (p63, cytokeratin 5/6, cytokeratin 7, CDX2, MUC2, and MUC5AC) and 2 new markers, anterior gradient homolog 2 and SOX2, in esophageal carcinomas to establish the best panel to distinguish these tumors. Tissue microarrays with 69 esophageal adenocarcinomas and 41 whole sections of esophageal squamous cell carcinomas were stained for these markers and semiquantitatively scored. Sensitivities and specificities were calculated for individual markers and select combinations using the morphological diagnosis as a gold standard. All squamous cell carcinomas expressed p63 with 38 of 41 demonstrating reactivity in more than 75% of tumor cells. Cytokeratin 5/6 expression was seen in 40 of 41 squamous cell carcinomas with 39 of 41 demonstrating reactivity in more than 75% of tumor cells. SOX2 expression was present in 35 of 41 of squamous cell carcinomas but also in 24 of 69 of adenocarcinomas, frequently demonstrating extensive reactivity in adenocarcinomas. Anterior gradient homolog 2 was highly sensitive for adenocarcinoma and present in 68 of 69 of cases, but anterior gradient homolog 2 reactivity was also identified in 15 of 41 of squamous cell carcinomas, typically demonstrating focal reactivity in squamous cell carcinoma. MUC5AC expression was-seen almost exclusively in adenocarcinomas with only a single squamous cell carcinoma demonstrating focal MUC5AC staining. Overall, the dual expression of both p63 and cytokeratin 5/6 was 99% specific and 98% sensitive for squamous cell carcinoma. In addition, anterior gradient homolog 2 and MUC5AC are useful positive markers of adenocarcinoma in the setting of absent or diminished p63 and cytokeratin 5/6 staining. (c) 2012 Elsevier Inc. All rights reserved.