Cowan Morgan L, Li Qing K, Illei Peter B
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Appl Immunohistochem Mol Morphol. 2016 Jan;24(1):16-9. doi: 10.1097/PAI.0000000000000250.
Adenocarcinoma with enteric differentiation is a rare subtype of lung adenocarcinoma that is recognized as a variant type of primary adenocarcinoma in the 2015 World Health Organization classification of lung tumors. Published immunohistochemistry studies show variable staining pattern for CDX-2 ranging from positivity in 71% of the cases to no staining. As little is known about CDX-2 expression in lung adenocarcinomas lacking histologic features of enteric differentiation, our aim was to determine the rate of CDX-2 positivity in non-enteric-type lung adenocarcinomas. We performed immunohistochemistry for CDX-2, CK7, CK20, TTF-1, napsin A, and p40 using 4-μm sections of a previously constructed tissue microarray containing 93 primary lung adenocarcinomas that lack morphologic evidence of enteric differentiation. The cohort included 22 well, 54 moderately, and 17 poorly differentiated tumors (55 female, 38 male; age range: 42 to 86, median: 64.5). All 93 tumors were strongly CK7 positive, whereas variable CK20 staining was seen in 4 tumors (1 strong, 1 moderate, and 2 focal). Both TTF-1 and napsin A were positive in 81 of 93 (87%) tumors with only 6 of 93 (6.5%) tumors negative for both the markers. Eleven tumors were CDX-2 positive (5 strong, 3 moderate, and 3 weak), all of which were also TTF-1 and napsin A positive and p40 negative. One CDX-2-positive tumor showed focal CK20 staining. Mutation studies for EGFR/K-ras/ALK were performed in four CDX-2-positive tumors and detected a K-ras mutation in one of them. CDX-2 positivity can be seen in a subset (12%) of lung adenocarcinoma. These tumors are CK7, TTF-1, and napsin A positive and p40 negative. Focal CK20 staining is only seen in rare cases. CDX-2 positivity should not be used as the only criteria to exclude lung origin.
具有肠化生分化的腺癌是肺腺癌的一种罕见亚型，在2015年世界卫生组织肺肿瘤分类中被视为原发性腺癌的一种变异类型。已发表的免疫组化研究显示，CDX-2的染色模式各不相同，阳性率从71%到无染色不等。由于对缺乏肠化生分化组织学特征的肺腺癌中CDX-2表达了解甚少，我们的目的是确定非肠型肺腺癌中CDX-2的阳性率。我们使用先前构建的包含93例缺乏肠化生分化形态学证据的原发性肺腺癌的组织芯片的4μm切片，对CDX-2、CK7、CK20、TTF-1、 napsin A和p40进行了免疫组化。该队列包括22例高分化、54例中分化和17例低分化肿瘤（55例女性，38例男性；年龄范围：42至86岁，中位数：64.5岁）。所有93例肿瘤均CK7强阳性，而4例肿瘤（1例强阳性、1例中等阳性和2例局灶性阳性）可见CK20染色不一。93例肿瘤中有81例（87%）TTF-1和napsin A均为阳性，只有93例中的6例（6.5%）两种标志物均为阴性。11例肿瘤CDX-2阳性（5例强阳性、3例中等阳性和3例弱阳性），所有这些肿瘤TTF-1和napsin A也为阳性且p4O阴性。1例CDX-2阳性肿瘤显示局灶性CK20染色。对4例CDX-2阳性肿瘤进行了EGFR/K-ras/ALK突变研究，其中1例检测到K-ras突变。在一部分（12%）肺腺癌中可出现CDX-2阳性。这些肿瘤CK7、TTF-1和napsin A阳性且p40阴性。仅在罕见病例中可见局灶性CK20染色。CDX-2阳性不应作为排除肺源性的唯一标准。
