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.
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.
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.
We characterized two Shiga toxin-producing Escherichia coli (STEC) O86:HNM isolates from a patient with hemolytic uremic syndrome (HUS) or bloody diarrhea. Both of them did not possess the eaeA gene. However, the isolate from a HUS patient carried genetic markers of enteroaggregative E. coli (EAEC) and showed aggregative adherence pattern to HEp-2 cells. The other isolate from bloody diarrhea, which was negative with EAEC markers, was diffusely adhered to HEp-2 cells. The stx2 gene in both E. coli O86:HNM strains was encoded in each infectious phage, which was partially homologous to that of strain EDL933, a STEC O157:H7. These results will help to explain the genotypic divergences of STEC.
Focal nodular hyperplasia (FNH) of the liver is considered to develop as a hyperplastic response to a preexisting vascular abnormality. From the pathogenic point of view, we studied histological alterations in the extranodular background liver tissue of FNH (FNH-bg-liver). We compared ten FNH-bg-livers with ten non-FNH cases (non-FNH-liver) and found small uniform nodule formations with ring-like siderosis in the FNH-bg-livers (4/7, 57%) but not in the non-FNH-livers. Abnormal small arteries not accompanied by portal tracts were observed in six of six FNH-bg-livers for which immunohistochemical study was available, while this was observed in only three of the ten non-FNH-livers. CD34-positive sinusoids around the portal tracts were observed in only the FNH-bg-livers (3/6, 50%). Further, two of ten FNH-bg-livers had ectopic pancreatic tissue. Ring-like siderosis, abnormal small arteries, CD34-positive sinusoids, and ectopic pancreatic tissue were characteristic in the extranodular background liver tissue in cases of FNH.
A 7-month-old infant was noted to have vaginal bleeding that was accompanied by a discharged tumor fragment. The histological diagnosis was endodermal sinus tumor. Her serum alpha-fetoprotein (AFP) was increased to 358.7 ng/mL, and magnetic resonance imaging showed a 1.8 x 1.0 cm tumor in the vagina. She received combination chemotherapy with cyclophosphamide, pirarubicin, carboplatin, and etoposide. The tumor in the images disappeared and the serum level of AFP returned to the normal range after 2 cycles. Treatment was complete without surgical or radiological therapy. More than 45 months after the completion of chemotherapy, she is alive without signs of recurrence.
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