Yonezawa S, Sueyoshi K, Nomoto M, Kitamura H, Nagata K, Arimura Y, Tanaka S, Hollingsworth M A, Siddiki B, Kim Y S, Sato E
Second Department of Pathology, Kagoshima University School of Medicine, Kagoshima City, Japan.
Hum Pathol. 1997 Mar;28(3):344-52. doi: 10.1016/s0046-8177(97)90134-9.
We have previously reported that MUC2 apomucin was highly expressed in noninvasive tumors of the pancreas (intraductal papillary tumor [IdPT]) and liver (bile duct cystadenocarcinoma [BdCC]), which show more favorable outcomes than invasive carcinomas. In contrast, MUC2 was rarely expressed in invasive carcinomas of the pancreas (invasive ductal carcinoma [IDC]) and the liver (invasive cholangiocarcinoma [ICC]). In the present study, we examined localization of MUC2 messenger RNA (MUC2 mRNA) by using a complementary DNA (cDNA) probe for the MUC2 tandem repeat for in situ hybridization (pHAM1). Localization of MUC2 apomucin was determined by using an antibody directed against MUC2 apomucin (anti-MRP) for immunohistochemistry study. Eleven IdPTs and 10 IDCs of the pancreas, and 8 BdCC and 8 ICCs of the liver were examined. Nine (82%) of 11 IdPTs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the IDCs showed expression of MUC2 mRNA. Six (75%) of the 8 BdCCs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the 8 ICCs showed expression of MUC2 mRNA. The localization of MUC2 mRNA and that of MUC2 apomucin usually coincided, although a few cases (1 IDC, 1 BdCC, and 1 ICC) showed focal expression of MUC2 apomucin despite the absence of detectable MUC2 mRNA. These results indicate that the expression of MUC2 apomucin in IdPTs and BdCCs correlates with expression of MUC2 mRNA. In both patient groups with pancreatic tumors and hepatic tumors, patients with positive MUC2 mRNA expression in the tumors showed significantly better survival than those with negative MUC2 mRNA expression in the tumors. The production of MUC2, an abundant extracellular mucin, by most IdPTs and BdCCs may be correlated with tumors that display lower levels of invasion and metastasis.
我们之前曾报道，MUC2脱辅基粘蛋白在胰腺的非侵袭性肿瘤（导管内乳头状肿瘤[IdPT]）和肝脏的非侵袭性肿瘤（胆管囊腺癌[BdCC]）中高表达，这些肿瘤的预后比侵袭性癌更好。相比之下，MUC2在胰腺的侵袭性癌（浸润性导管癌[IDC]）和肝脏的侵袭性癌（浸润性胆管癌[ICC]）中很少表达。在本研究中，我们通过使用针对MUC2串联重复序列的互补DNA（cDNA）探针（pHAM1）进行原位杂交，检测了MUC2信使核糖核酸（MUC2 mRNA）的定位。通过使用针对MUC2脱辅基粘蛋白的抗体（抗MRP）进行免疫组织化学研究，确定了MUC2脱辅基粘蛋白的定位。对11例胰腺IdPT和10例胰腺IDC，以及8例肝脏BdCC和8例肝脏ICC进行了检查。11例IdPT中有9例（82%）在肿瘤细胞中显示MUC2 mRNA阳性表达，而10例IDC中无一例（0%）显示MUC2 mRNA表达。8例BdCC中有6例（75%）在肿瘤细胞中显示MUC2 mRNA阳性表达，而8例ICC中无一例（0%）显示MUC2 mRNA表达。MUC2 mRNA的定位与MUC2脱辅基粘蛋白的定位通常一致，尽管有少数病例（1例IDC、1例BdCC和1例ICC）在未检测到MUC2 mRNA的情况下仍显示MUC2脱辅基粘蛋白的局灶性表达。这些结果表明，IdPT和BdCC中MUC2脱辅基粘蛋白的表达与MUC2 mRNA的表达相关。在胰腺肿瘤和肝脏肿瘤患者组中，肿瘤中MUC2 mRNA表达阳性的患者的生存率明显高于肿瘤中MUC2 mRNA表达阴性的患者。大多数IdPT和BdCC产生的大量细胞外粘蛋白MUC2可能与侵袭和转移水平较低的肿瘤相关。
