Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs - Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas
Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs - Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas
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DOI：
10.1097/00000478-200305000-00002
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发表时间：
2003-05-01
影响因子：
5.6
通讯作者：
Klimstra, DS
中科院分区：
文献类型：
--
作者：
Adsay, NV;Merati, K;Klimstra, DS
在外分泌器官中。乳腺和胰腺胶质癌（CC，纯粘液癌）。以边界清楚的粘液湖为特征，含有少量分离的恶性细胞。具有比常规导管癌（DC）显著更好的预后。我们和其他人推测，细胞的反向极化可能是细胞外粘蛋白积累的原因。另一种可能性是这种粘蛋白在生物化学和生物学上与这些器官的常规癌分泌的粘蛋白不同。进行本研究以调查以下两个假设：1）为了测试CC中是否确实存在细胞极性的改变。管腔表面糖蛋白的免疫组织化学染色在IS胰腺和30例乳腺CC中进行了胰腺癌胚抗原和乳腺MUC1的表达，并与DC中的表达模式进行了比较结果显示这些糖蛋白主要表达在CC细胞的面向基质的表面，与DC相反，其中表达在腔表面（在分化良好的区域）或分散在整个细胞中，在分化差的区域的胞浆内。对10个乳腺和2个胰腺CC进行的超微结构检查显示，在所有情况下，在面向基质的表面都有粘液原颗粒（通常位于顶端型细胞膜之下）凝结。相比之下，在DC（5个胰腺和5个乳腺）中，在任何情况下，在面向基质的细胞质中均未鉴定到粘液素颗粒的聚集。在所有CC中均未检测到外板层或基底膜，而在DC中，明显的（10个中的3个）或不连续的（10个中的4个）外板层将肿瘤细胞与基质分离。2)为了确定MUC2在CC中的表达频率并将其与DC和正常组织中的MUC2表达频率进行比较，进行MUC2（克隆ccp58）的免疫组织化学染色。MUC2在18例胰腺癌中的18例和30例乳腺癌中的30例中表达，而在DC中的表达非常罕见（136例胰腺DC中的1例和47例乳腺癌中的3例，p
In the exocrine organs. breast and pancreas, colloid carcinoma (CC, pure mucinous carcinoma). characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells. has a significantly better prognosis than conventional ductal carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional carcinomas of these organs, This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in IS pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts, The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen,granules was identified in the cytoplasm facing the stroma in any of the cases, Furthermore. no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (I of 136 pancreatic DC and 3 of 47 mammary, p