In previous studies of the expression of MUC1 (membrane-bound type mucin) and MUC2 (intestinal type secretory mucin) in pancreatic tumours, invasive ductal carcinoma (IDC) usually showed MUC1+ and MUC2- expression, whereas intraductal papillary-mucinous tumour (IPMT) showed MUC1- and MUC2+ expression. Recently, however, many IPMTs have been collected, a considerable number of which have shown MUC1- and MUC2- expression. In the present study, the clinicopathological features were examined of 18 IPMTs with MUC2+ and 32 IPMTs with MUC2-, and their potential for malignancy was compared. Most of the IPMTs with MUC2+ were composed of dark columnar cells, whereas most of the IPMTs with MUC2- were composed of clear columnar cells. The incidence of carcinomatous change and invasive proliferation of the carcinoma in the MUC2+ tumours was significantly higher than in the MUC2- tumours. The clinical outcome for the patients with IPMT showing the MUC2+ pattern tended to be worse than for those with IPMT showing the MUC2- pattern, although the overall outcome for the two types of IPMT was significantly better than for those with IDC. Because of the differences in mucin expression pattern, morphological appearance and potential for malignancy between the two types of IPMT, we believe that they belong to different neoplastic lineages and that it may be reasonable to classify them as different entities, although the WHO classification contains a single clinicopathological entity of IPMT forming an adenoma-carcinoma sequence. In conclusion, our classification of IPMTs by MUC2 expression pattern may be of value in the better assessment of the biological behaviour of IPMTs and their potential for malignancy.
Background: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. Aims: To investigate the prognostic significance of MUC4 expression in IDC. Methods: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. Results: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (.20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (,20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (.T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. Conclusions: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.
In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary-mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.
Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P< 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2- expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P< 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be
Our previous studies of pancreatic tumors have demonstrated that invasive ductal carcinoma (IDC) usually showed expression of MUC1 (membrane bound type mucin) detected by monoclonal antibody DF3, whereas intraductal papillary-mucinous neoplasm (IPMN) showed no expression of MUC1. In the present study, we examined 50 IDCs, and 63 IPMNs which were morphologically classified into two histological subtypes, "dark cell type" (IPMN-D, 27 cases) and "clear cell type" (IPMN-C, 36 cases). Patients with either type of IPMN showed significantly better survival than those with IDC. To clarify the relationship of the expression patterns of mucins with their biological behavior, we examined the expression profiles of various glycoforms of membrane mucin (MUC1) and secretory mucin (MUC2, MUC5AC and MUC6) in the neoplasms using immunohistochemistry. IDCs showed high expression of all the glycoforms of MUC1 (66%-98%). In contrast, IPMNs-D showed no or low expression of all the glycoforms of MUC1 (0%-4%), while IPMNs-C showed low expression of poorly glycosylated MUC1 (3%-6%), but expression of sialylated MUC1 (41%) and fully glycosylated MUC1 (69%). Expression of MUC2 was negative (0%) in IDC, high (96%) in IPMN-D and low (3%) in IPMN-C. MUC5AC was highly expressed in all types. MUC6 expression was higher in IPMNs-C (92%) than in IDCs (56%) and IPMNs-D (37%). In conclusion, the present study demonstrated that IDCs showed high expression of all the glycoforms of MUC1, and also that two types of IPMNs showed different expression patterns of glycosylated MUC1 as well as MUC2 and MUC6. These different expression patterns of mucins may be related with the malignancy potential of pancreatic neoplasms.
Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.
Our study of the mucin expression pattern in IDC and IPMN shows that this pattern may be related to the biological behavior of pancreatic tumors and their malignant potential.
Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas.
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