Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma
Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma
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DOI：
10.1038/modpathol.2009.15
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发表时间：
2009-05-01
期刊：
影响因子：
7.5
通讯作者：
Witkiewicz, Agnieszka K.
中科院分区：
文献类型：
--
作者：
Brody, Jonathan R.;Costantino, Christina L.;Witkiewicz, Agnieszka K.
胰腺腺鳞癌是最具侵袭性的胰腺癌之一。这种罕见肿瘤亚型的分子特征很少。了解胰腺腺鳞癌的常见分子和病理特征可以为确定治疗靶点提供关键信息。在此，我们分析了八种胰腺腺鳞癌系列的病理和分子特征。我们在所有 8 例病例中均发现 KRAS2 基因在密码子 12 处发生突变。所有病例均显示p16蛋白缺失。其中三个病例的丢失归因于 p16/CDKN2a 基因中的外显子 2 纯合缺失。大多数病例有 Dpc4 蛋白缺失和强核 p53 阳性，类似于胰腺导管腺癌中发现的分子特征。我们发现，在所有病例中，E-钙粘蛋白都丢失或减少，并且表皮生长因子受体在所有病例中都过度表达。鳞状成分对 p63 染色呈阳性，因此 p63 标记有助于识别具有棘层松解生长模式的腺鳞癌的鳞状细胞分化。总之，尽管胰腺腺鳞癌和导管腺癌具有重叠的病理和分子特征，但存在明显的差异，可能有助于诊断和治疗策略。现代病理学(2009) 22, 651-659; doi：10.1038/modpathol.2009.15； 2009 年 3 月 6 日在线发布
Adenosquamous carcinoma of the pancreas is one of the most aggressive forms of pancreatic cancer. Molecular characterizations of this rare tumor subtype are sparse. Understanding the common molecular and pathologic features of pancreatic adenosquamous carcinomas could provide critical information for identifying therapeutic targets. Herein, we analyzed the pathologic and molecular features of our series of eight pancreatic adenosquamous carcinomas. We found KRAS2 gene mutations at codon 12 in all eight cases. All the cases showed loss of p16 protein. In three of these cases the loss was attributed to an exon 2 homozygous deletion in the p16/CDKN2a gene. The majority of the cases had loss of Dpc4 protein and strong nuclear p53 positivity, similar to the molecular signature found in pancreatic ductal adenocarcinoma. We found that E-cadherin was either lost or reduced in all cases and that epidermal growth factor receptor was overexpressed in all cases. The squamous component was positive for p63 staining and thus p63 labeling was helpful in identifying squamous differentiation in adenosquamous carcinomas with an acantholytic growth pattern. In summary, although pancreatic adenosquamous carcinoma and ductal adenocarcinoma have overlapping pathologic and molecular characteristics, there are distinct differences that may be helpful in diagnostic and therapeutic strategies. Modern Pathology (2009) 22, 651-659; doi: 10.1038/modpathol.2009.15; published online 6 March 2009