The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: Differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis
The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: Differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis
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DOI：
10.1097/01.mp.0000028647.98725.8b
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发表时间：
2002-10-01
期刊：
影响因子：
7.5
通讯作者：
Klimstra, DS
中科院分区：
文献类型：
--
作者：
Adsay, NV;Merati, K;Klimstra, DS
新出现的证据表明，在胰腺的异型增生-CIS-浸润性癌序列的二分法。胰腺上皮内肿瘤（PanIN;小的偶发性导管病变）进展为浸润性导管腺癌（5年生存率为55%）。我们通过检测MUC 1和MUC 2的表达来探讨这些病变之间的关系，据报道，MUC 1和MUC 2分别反映了胰腺癌中的“侵袭性”和“惰性”表型。用MUC 1（克隆Ma 695）和MUC 2（克隆Ccp 58）抗体对PanIN（n=43）、导管内乳头状粘液性肿瘤（n=74）、导管腺癌（n=136）和胶样癌（n=15）进行免疫组织化学标记。54%的导管内乳头状粘液性肿瘤表达MUC 2，而PanIN则无一表达。相比之下，PanIN，尤其是高级别病变，MUC 1通常呈阳性（PanIN 3的61%），而这种糖蛋白的表达在导管内乳头状粘液性肿瘤中不常见（20%）。这种二分法在浸润性癌中进一步突出，这两种浸润前途径分别与之相关：所有胶质癌均为MUC 2+（100%）和MUC 1-（0%），而导管腺癌的标记模式则相反：63%为MUC 1+，仅1%为MUC 2+。这些结果支持了胰腺发育不良-CIS序列的二分法。由于这两种途径通常导致不同类型的浸润性癌，因此这是研究癌发生的宝贵模型。这里的发现也支持了以前的印象，MUC 2（与凝胶形成相关的粘蛋白）是“惰性”途径（导管内乳头状粘液性肿瘤和胶质癌）的标志物，而MUC 1（已知在细胞-细胞和细胞-基质相互作用以及肿瘤细胞的免疫抗性中具有抑制作用的糖蛋白）是“侵袭性”途径（PanIN至导管腺癌）的标志物。
Emerging evidence suggests a dichotomy in the dysplasia-CIS-invasive carcinoma sequence in the pancreas. Pancreatic intraepithelial neoplasms (PanINs; small, incidental duct lesions) progress to invasive ductal adenocarcinomas (5-y survival of 55%). We explored the relationship of these lesions by examining the expression of MUC1 and MUC2, glycoproteins reportedly reflecting "aggressive" and "indolent" phenotypes in pancreas cancer, respectively. Immunohistochemical labeling with MUC1 (clone Ma695) and MUC2 (clone Ccp58) antibodies was performed on PanINs (n=43), intraductal papillary mucinous neoplasms (n=74), ductal adenocarcinomas (n=136), and colloid carcinomas (n=15). Fifty-four percent of the intraductal papillary mucinous neoplasms expressed MUC2, whereas none of the PanINs did. In contrast, PanINs, especially higher grade lesions, were often positive for MUC1 (61% of PanIN 3), whereas the expression of this glycoprotein was infrequent in intraductal papillary mucinous neoplasms (20%). This dichotomy was further accentuated in the invasive carcinomas with which these two preinvasive pathways are respectively associated: all colloid carcinomas were MUC2+ (100%) and MUC1- (0%), whereas the labeling pattern was the reverse for ductal adenocarcinomas: 63% were MUC1+ and only 1% were MUC2+. These results support a dichotomy in the dysplasia-CIS sequence in the pancreas. Because these two pathways often lead to different types of invasive carcinomas, this is an invaluable model for the study of carcinogenesis. The findings here also support the previous impression that MUC2 (the mucin associated with gel formation) is a marker of the "indolent" pathway (intraductal papillary mucinous neoplasm and colloid carcinoma), whereas MUC1 (the glycoprotein known to have an inhibitory role in cell-cell and cell-stroma interactions as well as in immunoresistance of tumor cells) is a marker of the "aggressive" pathway (PanIN to ductal adenocarcinoma).