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Quasimesenchymal phenotype predicts systemic metastasis in pancreatic ductal adenocarcinoma.
Modern Pathology ( IF 7.1 ) Pub Date : 2019-01-25 , DOI: 10.1038/s41379-018-0196-2 Krishnan K Mahadevan 1 , Kshitij S Arora 1 , Arnaud Amzallag 2 , Erik Williams 1 , Anupriya S Kulkarni 3 , Carlos Fernandez-Del Castillo 4 , Keith D Lillemoe 4 , Nabeel Bardeesy 3 , Theodore S Hong 5 , Cristina R Ferrone 4 , David T Ting 3 , Vikram Deshpande 1
Modern Pathology ( IF 7.1 ) Pub Date : 2019-01-25 , DOI: 10.1038/s41379-018-0196-2 Krishnan K Mahadevan 1 , Kshitij S Arora 1 , Arnaud Amzallag 2 , Erik Williams 1 , Anupriya S Kulkarni 3 , Carlos Fernandez-Del Castillo 4 , Keith D Lillemoe 4 , Nabeel Bardeesy 3 , Theodore S Hong 5 , Cristina R Ferrone 4 , David T Ting 3 , Vikram Deshpande 1
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Metastasis following surgical resection is a leading cause of mortality in pancreatic ductal adenocarcinoma. Epithelial-mesenchymal transition is thought to play an important role in metastasis, although its clinical relevance in metastasis remains uncertain. We evaluated a panel of RNA in-situ hybridization probes for epithelial-mesenchymal transition-related genes expressed in circulating tumor cells. We assessed the predictive value of this panel for metastasis in pancreatic ductal adenocarcinoma and, to determine if the phenotype is generalizable between cancers, in colonic adenocarcinoma. One hundred fifty-eight pancreatic ductal adenocarcinomas and 205 colonic adenocarcinomas were classified as epithelial or quasimesenchymal phenotype using dual colorimetric RNA-in-situ hybridization. SMAD4 expression on pancreatic ductal adenocarcinomas was assessed by immunohistochemistry. Pancreatic ductal adenocarcinomas with quasimesenchymal phenotype had a significantly shorter disease-specific survival (P = 0.031) and metastasis-free survival (P = 0.0001) than those with an epithelial phenotype. Pancreatic ductal adenocarcinomas with SMAD4 loss also had lower disease-specific survival (P = 0.041) and metastasis-free survival (P = 0.001) than those with intact SMAD4. However, the quasimesenchymal phenotype proved a more robust predictor of metastases-area under the curve for quasimesenchymal = 0.8; SMAD4 = 0.6. The quasimesenchymal phenotype also predicted metastasis-free survival (P = 0.004) in colonic adenocarcinoma. Epithelial-mesenchymal transition defined two phenotypes with distinct metastatic capabilities-epithelial phenotype tumors with predominantly organ-confined disease and quasimesenchymal phenotype with high risk of metastatic disease in two epithelial malignancies. Collectively, this work validates the relevance of epithelial-mesenchymal transition in human gastrointestinal tumors.
中文翻译：
准间充质表型预测胰腺导管腺癌的全身转移。
手术切除后的转移是胰腺导管腺癌死亡的主要原因。上皮间质转化被认为在转移中发挥重要作用，尽管其在转移中的临床相关性仍不确定。我们评估了一组 RNA 原位杂交探针，用于检测循环肿瘤细胞中表达的上皮间质转化相关基因。我们评估了该组对胰腺导管腺癌转移的预测价值，并确定该表型在结肠腺癌中是否可在癌症之间推广。使用双比色 RNA 原位杂交将 158 例胰腺导管腺癌和 205 例结肠腺癌分类为上皮或准间充质表型。通过免疫组织化学评估胰腺导管腺癌中 SMAD4 的表达。与具有上皮表型的胰腺导管腺癌相比，具有准间充质表型的胰腺导管腺癌的疾病特异性生存期（P = 0.031）和无转移生存期（P = 0.0001）显着缩短。 SMAD4 缺失的胰腺导管腺癌的疾病特异性生存率 (P = 0.041) 和无转移生存率 (P = 0.001) 也低于 SMAD4 完整的胰腺导管腺癌。然而，准间充质表型被证明是曲线下转移面积的更稳健的预测因子，准间充质 = 0.8； SMAD4 = 0.6。准间充质表型还预测结肠腺癌的无转移生存期（P = 0.004）。 上皮-间质转化定义了两种具有不同转移能力的表型——主要是器官局限性疾病的上皮表型肿瘤和两种上皮恶性肿瘤中具有高转移风险的准间质表型。总的来说，这项工作验证了人类胃肠道肿瘤中上皮间质转化的相关性。
更新日期：2019-01-26
中文翻译：
准间充质表型预测胰腺导管腺癌的全身转移。
手术切除后的转移是胰腺导管腺癌死亡的主要原因。上皮间质转化被认为在转移中发挥重要作用，尽管其在转移中的临床相关性仍不确定。我们评估了一组 RNA 原位杂交探针，用于检测循环肿瘤细胞中表达的上皮间质转化相关基因。我们评估了该组对胰腺导管腺癌转移的预测价值，并确定该表型在结肠腺癌中是否可在癌症之间推广。使用双比色 RNA 原位杂交将 158 例胰腺导管腺癌和 205 例结肠腺癌分类为上皮或准间充质表型。通过免疫组织化学评估胰腺导管腺癌中 SMAD4 的表达。与具有上皮表型的胰腺导管腺癌相比，具有准间充质表型的胰腺导管腺癌的疾病特异性生存期（P = 0.031）和无转移生存期（P = 0.0001）显着缩短。 SMAD4 缺失的胰腺导管腺癌的疾病特异性生存率 (P = 0.041) 和无转移生存率 (P = 0.001) 也低于 SMAD4 完整的胰腺导管腺癌。然而，准间充质表型被证明是曲线下转移面积的更稳健的预测因子，准间充质 = 0.8； SMAD4 = 0.6。准间充质表型还预测结肠腺癌的无转移生存期（P = 0.004）。 上皮-间质转化定义了两种具有不同转移能力的表型——主要是器官局限性疾病的上皮表型肿瘤和两种上皮恶性肿瘤中具有高转移风险的准间质表型。总的来说，这项工作验证了人类胃肠道肿瘤中上皮间质转化的相关性。
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