Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biliary cystic tumors, which are also called biliary cystadenoma and cystadenocarcinoma, are thought to be a heterogeneous disease entity, and some of them are known to show a luminal communication to the bile duct. In this study, we examined the clinicopathological features of nine cases of biliary cystic tumors with bile duct communication. They were composed of five males and four females with an average age of 67 years (52-84 years). They were multilocular (eight cases) or unilocular (one case), and all cases contained mucinous fluid. A direct luminal communication with the bile ducts was identified in five cases on preoperative or intraoperative cholangiographies. Biliary cystic tumors examined in this study were histologically adenoma (one case), adenocarcinoma in situ (six cases), and adenocarcinoma associated with microinvasive mucinous carcinoma (two cases). One case of adenocarcinoma in situ also had the adenoma component (adenocarcinoma in adenoma). Dysplastic mucinous epithelium proliferated in flat, micropapillary and papillary fashions within the intracystic spaces. Intraepithelial neoplasm was observed within non-dilated adjacent bile ducts, suggesting a direct luminal communication between the cystic tumors and the bile duct. Ovarian-like stroma was not observed in their walls in any cases. Immunohistochemically, seven cases expressed MUC1 or MUC2 in the neoplastic biliary epithelium. All cases except one were alive without any evidences of tumor recurrence after total excision (3-156 months after surgery). These clinicopathological features resembled those of intraductal papillary neoplasm of the bile duct, which had been reported as a biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. In conclusion, biliary cystic tumors with bile duct communication could be regarded as intraductal papillary neoplasm with a prominent cystic dilatation of the bile duct and mucin retention, rather than true biliary cystic neoplasms.
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PMID:Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct. 1674 22

Chronic idiopathic inflammatory bowel disease (IBD) with extensive colonic involvement predisposes to the development of colorectal adenocarcinoma. Among the types of cancer occurring in this setting is an unusually well-differentiated low-grade tubuloglandular adenocarcinoma (LGTGA) that has not been studied systematically thus far. A review of 149 IBD-associated cancer resections performed at our institution yielded 17 patients (11%) with 21 tumors classified as LGTGA based on the following histologic characteristics: very well-differentiated small to medium diameter glands with round or tubular profiles, low-grade cytologic characteristics and absence or paucity of desmoplastic reaction. Twelve patients had ulcerative colitis, 4 Crohn disease, and 1 indeterminate colitis. Their median age was 41.5 years (range, 28 to 58 y). Five patients had separate synchronous cancers of conventional types. LGTGAs ranged from 0.4 to 10 cm in size and varied in gross appearance. They included 5 flat lesions that were not identified visually but were detected either by palpation of the unfixed surgical specimen (1 case) or histologically in random sections (4 cases). The invasive glands usually bore a close histologic resemblance to overlying low-grade or indefinite dysplastic crypts. Twelve carcinomas (57%) with well-defined superficial regions of LGTGA progressed histologically to conventional adenocarcinoma in deeper regions. These tumors were significantly more advanced than 9 carcinomas that maintained low-grade histology throughout. Follow-up of 13 patients (76%) for a mean 4.0 years (range, 0.75 to 9.0 y) disclosed 10 (77%) with favorable outcomes and 3 (23%) with adverse outcomes. Two adverse outcomes were attributable to synchronous advanced-stage conventional cancers and the third to progression from LGTGA to poorly differentiated adenocarcinoma. The mucosa overlying and surrounding LGTGA showed low-grade dysplasia (LGD) in 18 cases (86%), indefinite dysplasia with focal LGD in 1 case (5%), and LGD with focal high-grade dysplasia (HGD) in 2 cases (10%). Immunohistochemical studies disclosed expression of MUC2 in 72%, MUC6 in 0%, CK7 in 69%, and CK20 in 100%. Coexpression of CK7 and CK20 was conserved in regions of conventional adenocarcinoma derived from LGTGA. Silencing of immunohistochemical expression of hMLH1 occurred in 6 of 11 tumors tested (55%), implicating defective DNA replication error repair in their pathogenesis. We conclude that LGTGA is a distinct clinicopathologic entity characterized by direct derivation from LGD mucosa of IBD, very well-differentiated morphology, frequent coexpression of CK7 and CK20, and frequent silencing of hMLH1. Histologic progression from LGTGA to conventional types of adenocarcinoma parallels clinical progression to more aggressive neoplasia. The potential of LGD to give rise directly to LGTGA, and by way of LGTGA to more aggressive cancers, reinforces recommendations in favor of aggressive management of IBD patients diagnosed with LGD.
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PMID:Intestinal low-grade tubuloglandular adenocarcinoma in inflammatory bowel disease. 1686 75

Alpha-fetoprotein (AFP)-producing gastric cancer (AFP-GC) is a highly malignant variant of adenocarcinoma with aberrant hepatocellular phenotype. A detailed understanding of the regulation of its liver phenotype is lacking. Liver-enriched nuclear factors (LENFs) are implicated in the transcriptional regulation of AFP in the fetal liver. To investigate the regulatory role of LENFs in AFP-GCs, the expression of LENFs including CCAAT/enhancer binding protein (C/EBP)-beta, C/EBP-alpha, hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta and HNF-4alpha was investigated in 3 cell lines of AFP-GC and 7 cell lines of control GC. The liver activating protein (LAP), an activating isoform of C/EBP-beta, was predominantly expressed in AFP-GCs, whereas the liver inhibitory protein (LIP), an inhibitory isoform of C/EBP-beta, predominated in the control GCs. HNF-1alpha was relatively suppressed in AFP-GCs. HNF-4alpha was expressed in one of three AFP-GC cell lines. C/EBP-alpha and HNF-1beta were expressed at the same levels in both cell types of GC. AFP-GCs expressed a set of hepatocyte-related proteins (e.g., transferrin and albumin) while they still retained the several glandular cell-related proteins (e.g., MUC2). The induction of LIP reduced transferrin expression and induced CEA expression in an AFP-GC line. Collecting these results, it was suggested that the contribution of LENFs, especially isoforms of C/EBP-beta, is possibly important in phenotypic regulation of AFP-GCs.
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PMID:Expression of liver-enriched nuclear factors and their isoforms in alpha-fetoprotein-producing gastric carcinoma cells. 1690 65

Sessile serrated adenoma (SSA) is a newly characterized type of the large bowel adenoma. It arises in hyperplastic polyp (HP) and represents a precursor lesion of colorectal carcinoma with microsatellite instability. SSAs differ from common HPs by abnormal proliferation of the crypt epithelium and by nuclear atypia. We examined 15 SSAs from 15 patients. The age range was 25-80 years (average 60 years). Six patients were females and 9 were males. For comparison, we examined 10 conventional tubular adenomas and 10 common HPs with vesicular cells. The sites of SSAs were as follows: 8 in rectum, 4 in rectosigmoid colon, 1 in transverse colon, 1 next to mucinous carcinoma of ascending colon, 1 in anastomosis after resection of the transverse colon adenocarcinoma. The diameter of the lesions ranged from 5 to 12 mm. Histologically, SSAs showed asymmetrical proliferation of the epithelium, irregular shape of the crypts with their branching and some crypt dilatations especially in the basal parts of the crypts. Cellular atypia (dysplasia) was usually low. In 5 cases the nuclei were focally stratified and localized in the lower part of the cells. High-grade dysplasia was found only in SSA adjacent to mucinous adenocarcinoma. Immunohistochemically, SSAs showed secretion of gastrointestinal mucin expressing MUC2 and MUC5A. Both MUC2 and MUC5A were also positive in mucinous carcinoma. In previous studies these expressions were considered specific for serrated type of carcinogenesis. However, our study found positivity of MUC2 and MUC5A also in conventional adenomas. Expression of p53 in SSAs was minimal. SSAs have malignant potential comparable with conventional adenomas and for this reason they must be distinguished from HPs.
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PMID:Sessile serrated adenomas of the large bowel. Clinicopathologic and immunohistochemical study including comparison with common hyperplastic polyps and adenomas. 1695 61

Loss of intestinal mucosa integrity is an important factor in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to characterize expression changes and allelic variants of genes related to intestinal epithelial barrier function in this disease. Therefore, ileal and colonic mucosal biopsies from nonaffected regions of patients with ulcerative colitis (UC) and Crohn's disease (CD), as well as non-IBD probands, were subjected to Affymetrix DNA-microarray analysis. Real-time reverse transcription polymerase chain reaction was used for verification in larger IBD sample numbers. Disturbed mRNA expression was identified for several mucin genes in both disease groups and tissues. A significant downregulation in the colon was obtained for MUC2 in CD and MUC12 in CD and UC. Expression analysis of all dysregulated mucins in a broad human tissue panel revealed dominant epithelial tissue-specific transcription. In silico analysis of the regulatory regions of these mucins indicated nuclear factor kappaB (NFkappaB) binding sites in each promoter. Furthermore, NFkappaB was overrepresented in mucin promoters and a component of a specific combination of transcription factors (composite module). In vivo stimulation experiments in the adenocarcinoma cell line LS174T showed inducible mucin expression by the cytokines tumor necrosis factor-alpha and transforming growth factor-beta, which could be blocked by NFkappaB signaling inhibitors. Allelic discrimination screening obtained statistically significant associations for the MUC2-V116M (P = 0.003) polymorphism with CD and for MUC4-A585S (P = 0.025), as well as MUC13-R502S (P = 0.0003) with UC. These data suggest that the disturbed expression of mucin genes and the connection to the NFkappaB pathway may influence the integrity of the intestine and therefore contribute to the pathophysiology of IBD.
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PMID:Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. 1705 67

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.
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PMID:Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas. 1705 19

Intraductal papillary mucinous neoplasm (IPMN) is a unique pancreatic neoplasm developing in the ductal system. Two major histologic subtypes have been reported, that is the gastric type and the intestinal type. However, their histopathologic features, especially those of the gastric type, have not been fully described. To evaluate the features of these two types and refine their differences, we analyzed 80 IPMNs including 50 cases of the gastric type and 30 cases of the intestinal type with mucin immunohistochemistry. By defining a main duct-type lesion as predominantly involving the main pancreatic duct with or without branch ducts, and a branch duct-type lesion as exclusively centered on branch ducts or consisting of a collection of small cystic lesions, gastric-type IPMNs were mostly branch duct-type lesions (98%), whereas the intestinal-type IPMNs were usually main duct type (73%). The histologic grade of the intestinal type was generally higher than that of the gastric type. The intestinal type was also characterized by frequent intraluminal nodular growth, and severe atrophy and fibrosis of the surrounding parenchyma with mucous lake formation. In contrast, pyloric glandlike structures at the base of the papillae and pancreatic intraepithelial neoplasia (PanIN)-like complexes were more frequently observed in the gastric type. A significant difference was observed between the gastric type and the intestinal type with regard to all the above features (P<0.05). Seven cases (23%) of the intestinal type were associated with an invasive adenocarcinoma (6 mucinous and 1 ductal), versus only 1 case (2%) of the gastric type (invasive ductal carcinoma). All cases of both gastric and intestinal types expressed MUC5AC; however, high immunolabeling scores for MUC2 were mostly observed in the intestinal type (P<0.05). In conclusion, gastric and intestinal types of IPMNs have distinct histopathologic features and mucin profiles, suggesting that they may follow different biologic pathways.
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PMID:Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: its histopathologic difference between 2 major types. 1712 12

Infection with Helicobacter pylori cagA-positive strains is associated with gastric adenocarcinoma. Intestinal metaplasia is a precancerous lesion of the stomach characterized by transdifferentiation of the gastric mucosa to an intestinal phenotype. The H. pylori cagA gene product, CagA, is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Tyrosine-phosphorylated CagA specifically binds to and activates SHP-2 phosphatase, thereby inducing cell-morphological transformation. We report here that CagA physically interacts with E-cadherin independently of CagA tyrosine phosphorylation. The CagA/E-cadherin interaction impairs the complex formation between E-cadherin and beta-catenin, causing cytoplasmic and nuclear accumulation of beta-catenin. CagA-deregulated beta-catenin then transactivates beta-catenin-dependent genes such as cdx1, which encodes intestinal specific CDX1 transcription factor. In addition to beta-catenin signal, CagA also transactivates p21(WAF1/Cip1), again, in a phosphorylation-independent manner. Consequently, CagA induces aberrant expression of an intestinal-differentiation marker, goblet-cell mucin MUC2, in gastric epithelial cells that have been arrested in G1 by p21(WAF1/Cip1). These results indicate that perturbation of the E-cadherin/beta-catenin complex by H. pylori CagA plays an important role in the development of intestinal metaplasia, a premalignant transdifferentiation of gastric epithelial cells from which intestinal-type gastric adenocarcinoma arises.
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PMID:Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. 1723 8

Adenocarcinomas with intestinal differentiation have been described in a wide variety of anatomical sites. To our knowledge, however, ductal adenocarcinomas with intestinal phenotype have not been described in the pancreas. We report here 11 ductal carcinomas of the pancreas that were morphologically similar to colonic adenocarcinomas. These pancreatic carcinomas of intestinal type represented 10% of 110 consecutively removed ductal carcinomas of the pancreas. All intestinal type carcinomas expressed cytokeratin 7, carcinoembryonic antigen, CDX2, and MUC2. The pattern of reactivity of cytokeratin 7 and carcinoembryonic antigen was diffuse, whereas that of mucin 2 staining and CDX2 nuclear labeling was focal and confined predominantly to goblet cells and less frequently to columnar cells. Six carcinomas contained collections of endocrine cells admixed with the columnar and goblet cells. Five carcinomas were associated with high-grade pancreatic intraepithelial neoplasia of intestinal type. Six patients were female and 5 were male. Their ages ranged from 52 to 76 years (mean age, 61 years). The clinical presentation did not differ from that of the conventional ductal carcinomas. All carcinomas originated in the head of the pancreas, and 5 had metastasized to the regional lymph nodes at the time of surgical resection. Only 1 patient survived 5 years. Three patients are disease free from 2.8 to 8.9 months after surgery. Six patients died as a direct result of the carcinomas, and 1 was lost to follow-up. More studies are needed to determine the biologic behavior of this distinctive histologic variant of ductal adenocarcinoma of the pancreas.
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PMID:Intestinal type adenocarcinoma: a previously unrecognized histologic variant of ductal carcinoma of the pancreas. 1724 Mar

Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P=0.0006 and 72.2 vs 55.3%, P=0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P=0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P=0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P=0.0402 and 51.5 vs 84.6%, P=0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P=0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.
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PMID:Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach. 1726 83


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