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Suguru Yonezawa - One of the best experts on this subject based on the ideXlab platform.
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mucins in human neoplasms clinical pathology gene expression and diagnostic application
Pathology International, 2011Co-Authors: Suguru Yonezawa, Michiyo Higashi, Norishige Yamada, Sho Kitamoto, Seiya Yokoyama, Shinichi Kitajima, Masamichi GotoAbstract:Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. Our immunohistochemical studies demonstrated that MUC1 or MUC4 expression is related to the aggressive behavior and poor outcome of human neoplasms. MUC2 is expressed in indolent pancreatobiliary neoplasms, but these tumors sometimes show invasive growth with MUC1 expression in invasive areas. MUC5AC shows de novo high expression in many types of precancerous lesions of pancreatobiliary cancers and is an effective marker for early detection of the neoplasms. The combination of MUC1, MUC2, MUC4 and MUC5AC expression may be useful for early detection and evaluation of the potential for malignancy of pancreatobiliary neoplasms. Regarding the mechanism of mucin expression, we have recently reported that expression of the mucin genes is regulated epigenetically in cancer cell lines, using quantitative MassARRAY analysis, methylation-specific polymerase chain reaction analysis and chromatin immunoprecipitation analysis, with confirmation by the treatment with 5-aza-2′-deoxycytidine and trichostatin A. We have also developed a monoclonal antibody against the MUC1 cytoplasmic tail domain, which has many biological roles. Based on all of the above findings, we suggest that translational research into mucin gene expression mechanisms, including epigenetics, may provide new tools for early and accurate detection of human neoplasms.
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expression profiles of muc1 MUC2 and muc4 mucins in human neoplasms and their relationship with biological behavior
Proteomics, 2008Co-Authors: Suguru Yonezawa, Michiyo Higashi, Norishige Yamada, Masamichi Goto, Mitsuharu NomotoAbstract:Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis or tumor invasion. To clarify the relationship of the expression patterns of mucins in human neoplasms with their biological behavior, we examined the expression profiles of MUC1, MUC2, and MUC4 mucins in various human neoplasms using immunohistochemistry and in situ hybridization, and compared them with clinicopathologic factors including outcome of the patients. MUC1 or MUC4 expression is related with the aggressive behavior of human neoplasms and a poor outcome of the patients. In contrast, MUC2 expression tends to be related with the indolent behavior of human neoplasms and a favorable outcome of the patients, although indolent pancreatobiliary neoplasms sometimes show invasive growth with MUC1 expression in the invasive areas. The expression of MUC2 mucin in indolent pancreatobiliary neoplasms coincided with expression of MUC2 mRNA. Our recent studies to clarify the MUC2 gene regulation mechanism disclosed that DNA methylation and histone modification in the 5′ flanking region of the MUC2 promoter may play an important role. Further studies of the epigenetics also in MUC1 and MUC4 gene expression may be needed to understand the relationship between the expression of mucins in human neoplasms with their biological behavior.
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expression of mucins muc1 MUC2 muc5ac and muc6 in mucinous carcinoma of the breast comparison with invasive ductal carcinoma
Histopathology, 2003Co-Authors: Sumika Matsukita, Masamichi Goto, Eiichi Sato, Mitsuharu Nomoto, Tatsuro Irimura, Young S. Kim, Shinichi Kitajima, S Tanaka, Suguru YonezawaAbstract:Aims: Mucinous carcinoma of the breast usually shows less frequent lymph node metastasis and more favourable outcome compared with invasive ductal carcinoma. The aim of this study is to compare the expression profiles of several mucins in mucinous carcinomas and invasive ductal carcinomas to gain insight into the relationship between the less aggressive biological nature of mucinous carcinoma and the role of mucins. Methods and results: We examined the expression profiles of MUC1 (membrane-bound mucin) of different glycoforms (from non-glycosylated form to fully glycosylated form), MUC2 (intestinal type secretory mucin), MUC5AC (gastric surface type secretory mucin) and MUC6 (gastric pyloric gland type secretory mucin) in 17 mucinous carcinomas and 46 invasive ductal carcinomas using immunohistochemistry. Various glycoforms of MUC1 were expressed frequently in both mucinous carcinomas (65–100%) and invasive ductal carcinomas (92–100%), although non-glycosylated MUC1 (MUC1/CORE) and fully glycosylated MUC1 (MUC1/HMFG-1) showed significantly lower expression rates in mucinous carcinomas compared with those in invasive ductal carcinomas. The expression rates of MUC2 (94%) and MUC6 (71%) in mucinous carcinomas were significantly higher than those of MUC2 (15%) and MUC6 (15%) in invasive ductal carcinomas. There was no significant difference in the expression rate of MUC5AC in mucinous carcinomas (12%) and that in invasive ductal carcinomas (4%). Conclusions: The expression rate of MUC1/CORE and MUC1/HMFG-1, which is related to poor prognosis in the gastric and colorectal cancers, is low in mucinous carcinomas. The high expression rate of gel-forming secretory mucins (MUC2 and MUC6) in mucinous carcinoma suggests that high production of these types of mucins may act as a barrier to cancerous extension resulting in their less aggressive biological behaviour.
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expression of muc1 and MUC2 mucins in extrahepatic bile duct carcinomas its relationship with tumor progression and prognosis
Pathology International, 2002Co-Authors: Shugo Tamada, Masamichi Goto, Takeshi Shimizu, Sadao Tanaka, Koro Sakoda, Mitsuharu Nomoto, Koji Nagata, Kohzo Imai, Suguru YonezawaAbstract:Our previous immunohistochemical studies in the pancreas, intrahepatic bile duct, and ampulla of Vater demonstrated that an invasive carcinoma with a poor outcome showed a pattern of MUC1 (membrane-bound mucin) positive and MUC2 (intestinal-type secretory mucin) negative, whereas many of the non-invasive tumors with favorable outcome showed a pattern of MUC1 negative and MUC2 positive. The aim of this study is to compare the expression profiles of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas to gain insight into the relationship between the biological nature of the carcinomas and the role of mucins. We examined the expression profiles of MUC1 of different glycoforms and MUC2 in 60 extrahepatic bile duct carcinomas using immunohistochemistry. The expression of MUC1/CORE (core peptide of MUC1), MUC1/DF3 (core peptide of MUC1 with sialyl oligosaccharides) and MUC1/MY.1E12 (sialylated MUC1) showed a significant relationship with tumor progression factors such as poor differentiation, deep invasion, lymph node metastasis, lymphatic invasion or perineural invasion. In contrast, the expression of MUC1/HMFG-1 (fully glycosylated MUC1) did not show a significant relationship with the tumor progression factors. In the different glycoforms of MUC1 examined, the expression of MUC1/DF3 and MUC1/MY.1E12 was related with the poor outcome of the patients. In contrast, the expression of MUC2 was inversely related with the tumor progression factors and poor outcome. In the 52 patients with advanced tumors, only MUC1/DF3 high expression correlated with poor prognosis. In conclusion, MUC1/DF3 was the most useful prognosis indicator among the various glycoforms of MUC1 mucins.
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new classification of pancreatic intraductal papillary mucinous tumour by mucin expression its relationship with potential for malignancy
The Journal of Pathology, 2002Co-Authors: Akiko Nakamura, Masamichi Goto, Eiichi Sato, Koro Sakoda, Young S. Kim, Michiko Horinouchi, Kohji Nagata, Sonshin Takao, Kohzoh Imai, Suguru YonezawaAbstract: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. Copyright © 2002 John Wiley & Sons, Ltd.
Young S. Kim - One of the best experts on this subject based on the ideXlab platform.
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expression of mucins muc1 MUC2 muc5ac and muc6 in mucinous carcinoma of the breast comparison with invasive ductal carcinoma
Histopathology, 2003Co-Authors: Sumika Matsukita, Masamichi Goto, Eiichi Sato, Mitsuharu Nomoto, Tatsuro Irimura, Young S. Kim, Shinichi Kitajima, S Tanaka, Suguru YonezawaAbstract:Aims: Mucinous carcinoma of the breast usually shows less frequent lymph node metastasis and more favourable outcome compared with invasive ductal carcinoma. The aim of this study is to compare the expression profiles of several mucins in mucinous carcinomas and invasive ductal carcinomas to gain insight into the relationship between the less aggressive biological nature of mucinous carcinoma and the role of mucins. Methods and results: We examined the expression profiles of MUC1 (membrane-bound mucin) of different glycoforms (from non-glycosylated form to fully glycosylated form), MUC2 (intestinal type secretory mucin), MUC5AC (gastric surface type secretory mucin) and MUC6 (gastric pyloric gland type secretory mucin) in 17 mucinous carcinomas and 46 invasive ductal carcinomas using immunohistochemistry. Various glycoforms of MUC1 were expressed frequently in both mucinous carcinomas (65–100%) and invasive ductal carcinomas (92–100%), although non-glycosylated MUC1 (MUC1/CORE) and fully glycosylated MUC1 (MUC1/HMFG-1) showed significantly lower expression rates in mucinous carcinomas compared with those in invasive ductal carcinomas. The expression rates of MUC2 (94%) and MUC6 (71%) in mucinous carcinomas were significantly higher than those of MUC2 (15%) and MUC6 (15%) in invasive ductal carcinomas. There was no significant difference in the expression rate of MUC5AC in mucinous carcinomas (12%) and that in invasive ductal carcinomas (4%). Conclusions: The expression rate of MUC1/CORE and MUC1/HMFG-1, which is related to poor prognosis in the gastric and colorectal cancers, is low in mucinous carcinomas. The high expression rate of gel-forming secretory mucins (MUC2 and MUC6) in mucinous carcinoma suggests that high production of these types of mucins may act as a barrier to cancerous extension resulting in their less aggressive biological behaviour.
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new classification of pancreatic intraductal papillary mucinous tumour by mucin expression its relationship with potential for malignancy
The Journal of Pathology, 2002Co-Authors: Akiko Nakamura, Masamichi Goto, Eiichi Sato, Koro Sakoda, Young S. Kim, Michiko Horinouchi, Kohji Nagata, Sonshin Takao, Kohzoh Imai, Suguru YonezawaAbstract: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. Copyright © 2002 John Wiley & Sons, Ltd.
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Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: Its relationship with a new morphological classification of cholangiocarcinoma
Hepatology, 1999Co-Authors: Michiyo Higashi, Suguru Yonezawa, Sadao Tanaka, Tatsuro Irimura, Young S. Kim, Eiichi SatoAbstract:Our previous immunohistochemical study on intrahepatic bile duct tumors showed that invasive cholangiocarcinoma (ICC) with a poor outcome expressed MUC1 mucin but was negative for MUC2 mucin, whereas bile duct cystadenocarcinoma (BDCC) with a favorable outcome was MUC1 negative and MUC2 positive. In the present study, ICC was further subdivided into 2 subtypes: intraductal growth type and/or periductal infiltrating type (ICC-IP) and mass forming type (ICC-M). The survival of patients with BDCC or ICC-IP is significantly better than that of patients with ICC-M. We examined these subtypes (ICC-IP and ICC-M) and BDCC for their expression of MUC1 mucins of different glycoforms. ICC-M showed significantly higher MUC1 expression rates (90%, 95%, and 85% positive rates as measured with the DF3, MY.1E12, and MUC1-Glycoprotein antibodies, respectively) than BDCC and ICC-IP (14% and 33%, 58% and 58%, and 0% and 50% positive respectively, as measured by the same antibodies). In contrast, BDCC (86% positive) and ICC-IP (67% positive) showed significantly higher MUC2 expression rates than ICC-M (25% positive) as measured with the anti-MRP antibody. Thus, the immunohistochemical staining pattern of ICC-IP resembled the pattern of BDCC more than they resembled ICC-M. In general, MUC1 expression is associated with poor patient outcome, irrespective of the glycosylation status. In particular, high expression of more sialylated forms of MUC1 mucins was correlated with poor survival. In contrast, expression of non–sialylated MUC2 mucin is a favorable prognostic indicator. These results suggest that ICC-IP is a different entity from ICC-M. This reclassification may have value in determining prognosis and treatment method.
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expression of muc1 and MUC2 mucins in gastric carcinomas its relationship with the prognosis of the patients
Clinical Cancer Research, 1998Co-Authors: T Utsunomiya, Suguru Yonezawa, Tatsuro Irimura, Young S. Kim, S Tanaka, H Sakamoto, Hiroshi Kitamura, S Hokita, Takashi Aiko, Eiichi SatoAbstract:Our previous immunohistochemical studies for the expression of MUC1 mucin antigen (which was detected by monoclonal antibody DF3) and MUC2 mucin antigen (which was detected by polyclonal antibody anti-MRP) in pancreatic and intrahepatic bile duct tumors demonstrated that invasive carcinoma with poor outcome showed a pattern of MUC1+ and MUC2- expression, whereas many of the noninvasive tumors with favorable outcome showed a pattern of MUC1- and MUC2+ expression. To clarify the relationship between the expression of these mucin antigens and the biological properties of gastric cancers, the expression of MUC1 and MUC2 mucin antigens was examined immunohistochemically in 136 patients with gastric cancer invading the submucosa or the deeper layer, and the survival of the antigen-positive and antigen-negative patient groups was compared using the Kaplan-Meier method. For MUC1 mucin expression, different glycoforms of MUC1 were examined using four monoclonal antibodies (NCL-MUC-1-CORE, DF3, MY.1E12, and HMFG-1). The patients with MUC1+ mucin antigen staining in the carcinoma showed significantly worse survival than those with MUC1- mucin antigen staining. In contrast, the patients with MUC2+ mucin antigen staining in the carcinoma showed significantly better survival than those with MUC2- mucin antigen staining. In conclusion, MUC1 antigen expression was associated with a poor outcome in patients with gastric cancer, irrespective of its glycosylation status, and MUC1 is thus considered to be a useful prognostic factor for poor outcome in patients. In contrast, MUC2 antigen expression is a prognostic factor associated with a favorable outcome in patients. In addition, combined evaluation of the MUC1 and MUC2 mucin staining is clinically useful to predict outcome in patients with gastric cancer.
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expression of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from that in normal liver and extrahepatic biliary obstruction
Hepatology, 1998Co-Authors: M Sasaki, Yasuni Nakanuma, Young S. KimAbstract:Mucin plays an important role in the development of hepatoliths, which are formed within the intrahepatic large bile ducts. To date, eight apomucins, components of mucin, have been identified. The purpose of this study is to characterize the expression of MUC1, MUC2, MUC3, MUC5, and MUC6 apomucins at both the protein and messenger RNA (mRNA) levels in the intrahepatic large bile ducts and peribiliary glands in 36 livers from patients with hepatolithiasis, in 25 livers from the patients with extrahepatic biliary obstruction, and in 23 histologically-normal livers. MUC3 and MUC6 were constantly and focally expressed, respectively, in the biliary epithelial cells in the intrahepatic large bile ducts in normal livers, extrahepatic biliary obstruction, and, also, hepatolithiasis. In hepatolithiasis, MUC1, MUC2, and MUC5 apomucins were also focally expressed in 33%, 64%, and 89%, respectively, of the large intrahepatic bile ducts examined, whereas such expression was infrequent in normal livers and in extrahepatic biliary obstruction. The markedly proliferated intramural and extramural peribiliary glands in hepatolithiasis frequently expressed MUC3 and MUC6 apomucins and focally expressed MUC2 and MUC5 apomucins. All of the apomucins mRNA expression, except that of MUC1, resembled each protein expression. In conclusion, the characteristics of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from those in normal livers and extrahepatic biliary obstructrion. Increased expression of gel-forming mucins, such as MUC5 and MUC2, could be involved in the formation and development of hepatolithiasis.
Michiyo Higashi - One of the best experts on this subject based on the ideXlab platform.
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diagnosis of pancreatic neoplasms using a novel method of dna methylation analysis of mucin expression in pancreatic juice
PLOS ONE, 2014Co-Authors: Seiya Yokoyama, Michiyo Higashi, Sho Kitamoto, Yuko Goto, Taro Hara, Dai Ikebe, Taketo Yamaguchi, Yoshifumi Arisaka, Toru Niihara, Hiroto NishimataAbstract:Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. We have developed a novel ‘methylation-specific electrophoresis (MSE)’ method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of MUC1, MUC2 and MUC4 in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of MUC1, MUC2 and MUC4 were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87% and 80% for PDAC; 100% and 88% for intestinal-type IPMN; and 88% and 77% for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.
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Summary of the Data on the Expression of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in Clinicopathological Features of Appendiceal Carcinoma (n = 108).
2014Co-Authors: Hiroaki Shibahara, Michiyo Higashi, Seiya Yokoyama, Karine Rousseau, Iwao Kitazono, Masahiko Osako, Hiroshi Shirahama, Yukie Tashiro, Yasuhiro Kurumiya, Michihiko NaritaAbstract:apap, papillary adenocarcinoma; well, well differentiated adenocarcinoma; mod, moderately differentiated adenocarcinoma; por, poorly differentiated adenocarcinoma; sig, signet-ring cell carcinoma; muc, mucinous carcinoma.bm, mucosa; sm, submucosa; mp, muscularis propria; ss, subserosa, se, serosa; si, invasion to other organ.c27 cases without lymph node dissection were excluded.d3 cases with unknown details regarding curative or non-curative resection were excluded.Summary of the Data on the Expression of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in Clinicopathological Features of Appendiceal Carcinoma (n = 108).
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mucins in human neoplasms clinical pathology gene expression and diagnostic application
Pathology International, 2011Co-Authors: Suguru Yonezawa, Michiyo Higashi, Norishige Yamada, Sho Kitamoto, Seiya Yokoyama, Shinichi Kitajima, Masamichi GotoAbstract:Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. Our immunohistochemical studies demonstrated that MUC1 or MUC4 expression is related to the aggressive behavior and poor outcome of human neoplasms. MUC2 is expressed in indolent pancreatobiliary neoplasms, but these tumors sometimes show invasive growth with MUC1 expression in invasive areas. MUC5AC shows de novo high expression in many types of precancerous lesions of pancreatobiliary cancers and is an effective marker for early detection of the neoplasms. The combination of MUC1, MUC2, MUC4 and MUC5AC expression may be useful for early detection and evaluation of the potential for malignancy of pancreatobiliary neoplasms. Regarding the mechanism of mucin expression, we have recently reported that expression of the mucin genes is regulated epigenetically in cancer cell lines, using quantitative MassARRAY analysis, methylation-specific polymerase chain reaction analysis and chromatin immunoprecipitation analysis, with confirmation by the treatment with 5-aza-2′-deoxycytidine and trichostatin A. We have also developed a monoclonal antibody against the MUC1 cytoplasmic tail domain, which has many biological roles. Based on all of the above findings, we suggest that translational research into mucin gene expression mechanisms, including epigenetics, may provide new tools for early and accurate detection of human neoplasms.
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expression profiles of muc1 MUC2 and muc4 mucins in human neoplasms and their relationship with biological behavior
Proteomics, 2008Co-Authors: Suguru Yonezawa, Michiyo Higashi, Norishige Yamada, Masamichi Goto, Mitsuharu NomotoAbstract:Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis or tumor invasion. To clarify the relationship of the expression patterns of mucins in human neoplasms with their biological behavior, we examined the expression profiles of MUC1, MUC2, and MUC4 mucins in various human neoplasms using immunohistochemistry and in situ hybridization, and compared them with clinicopathologic factors including outcome of the patients. MUC1 or MUC4 expression is related with the aggressive behavior of human neoplasms and a poor outcome of the patients. In contrast, MUC2 expression tends to be related with the indolent behavior of human neoplasms and a favorable outcome of the patients, although indolent pancreatobiliary neoplasms sometimes show invasive growth with MUC1 expression in the invasive areas. The expression of MUC2 mucin in indolent pancreatobiliary neoplasms coincided with expression of MUC2 mRNA. Our recent studies to clarify the MUC2 gene regulation mechanism disclosed that DNA methylation and histone modification in the 5′ flanking region of the MUC2 promoter may play an important role. Further studies of the epigenetics also in MUC1 and MUC4 gene expression may be needed to understand the relationship between the expression of mucins in human neoplasms with their biological behavior.
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Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: Its relationship with a new morphological classification of cholangiocarcinoma
Hepatology, 1999Co-Authors: Michiyo Higashi, Suguru Yonezawa, Sadao Tanaka, Tatsuro Irimura, Young S. Kim, Eiichi SatoAbstract:Our previous immunohistochemical study on intrahepatic bile duct tumors showed that invasive cholangiocarcinoma (ICC) with a poor outcome expressed MUC1 mucin but was negative for MUC2 mucin, whereas bile duct cystadenocarcinoma (BDCC) with a favorable outcome was MUC1 negative and MUC2 positive. In the present study, ICC was further subdivided into 2 subtypes: intraductal growth type and/or periductal infiltrating type (ICC-IP) and mass forming type (ICC-M). The survival of patients with BDCC or ICC-IP is significantly better than that of patients with ICC-M. We examined these subtypes (ICC-IP and ICC-M) and BDCC for their expression of MUC1 mucins of different glycoforms. ICC-M showed significantly higher MUC1 expression rates (90%, 95%, and 85% positive rates as measured with the DF3, MY.1E12, and MUC1-Glycoprotein antibodies, respectively) than BDCC and ICC-IP (14% and 33%, 58% and 58%, and 0% and 50% positive respectively, as measured by the same antibodies). In contrast, BDCC (86% positive) and ICC-IP (67% positive) showed significantly higher MUC2 expression rates than ICC-M (25% positive) as measured with the anti-MRP antibody. Thus, the immunohistochemical staining pattern of ICC-IP resembled the pattern of BDCC more than they resembled ICC-M. In general, MUC1 expression is associated with poor patient outcome, irrespective of the glycosylation status. In particular, high expression of more sialylated forms of MUC1 mucins was correlated with poor survival. In contrast, expression of non–sialylated MUC2 mucin is a favorable prognostic indicator. These results suggest that ICC-IP is a different entity from ICC-M. This reclassification may have value in determining prognosis and treatment method.
Peiguo G Chu - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of vater adenocarcinoma application of cdx2 ck17 muc1 and MUC2
The American Journal of Surgical Pathology, 2005Co-Authors: Peiguo G Chu, Roderich E Schwarz, Sean K Lau, Yun Yen, Lawrence M WeissAbstract:Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.
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differential expression of muc1 MUC2 and muc5ac in carcinomas of various sites
American Journal of Clinical Pathology, 2004Co-Authors: Sean K Lau, Lawrence M Weiss, Peiguo G ChuAbstract:We studied immunohistochemical expression of MUC1, MUC2, and MUC5AC in 194 carcinomas of different primary sites to determine whether differential expression patterns could be used to distinguish different carcinomas. MUC1 was expressed by most (except adrenocortical and hepatocellular carcinomas). MUC2 was expressed infrequently (positive immunoreactivity primarily in tumors of gastrointestinal origin). MUC5AC was expressed by most pancreatic ductal and endocervical adenocarcinomas and a variable number of tumors of the gastrointestinal tract. A MUC1+/MUC2–/MUC5AC– immunophenotype was observed in most breast, lung, kidney, bladder, endometrial, and ovarian carcinomas; MUC1+/MUC2–/MUC5AC+ was characteristic of pancreatic ductal adenocarcinomas and cholangiocarcinomas. Adrenocortical and hepatocellular carcinomas were negative for all mucins. Carcinomas of gastrointestinal origin exhibited variable expression of each mucin examined and no consistent immunoreactivity pattern. Many carcinomas can exhibit distinct MUC1, MUC2, and MUC5AC expression patterns, which might be valuable diagnostically in specific settings (eg, distinguishing cholangiocarcinoma from hepatocellular carcinoma or renal from adrenocortical carcinoma). However, the overlapping and heterogeneous patterns of MUC1, MUC2, and MUC5AC expression observed in many tumors, particularly those of gastrointestinal origin, preclude use of these markers in the routine immunohistochemical assessment of carcinomas of an unknown primary site.
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differential expression of muc1 MUC2 and muc5ac in carcinomas of various sites an immunohistochemical study
American Journal of Clinical Pathology, 2004Co-Authors: Sean K Lau, Lawrence M Weiss, Peiguo G ChuAbstract:We studied immunohistochemical expression of MUC1, MUC2, and MUC5AC in 194 carcinomas of different primary sites to determine whether differential expression patterns could be used to distinguish different carcinomas. MUC1 was expressed by most (except
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immunohistochemical characterization of signet ring cell carcinomas of the stomach breast and colon
American Journal of Clinical Pathology, 2004Co-Authors: Peiguo G Chu, Lawrence M WeissAbstract:We studied the immunophenotype of signet-ring cell carcinoma (SRCC) of the stomach (30 cases), breast (21 cases), and colon (9 cases) with the following expression patterns: (1) breast: consistent, MUC1 (21 [100%]), cytokeratin (CK) 7 (20 [95%]), estrogen receptor (ER; 17 [81%]); infrequent, E-cadherin (6 [29%]), MUC2, MUC5AC, CK20 (1 [5%] each); negative, CDX2 and hepatocyte paraffin 1 (Hep Par 1; 0 [0%] each); (2) gastric: frequent, CDX2 (27 [90%]) and Hep Par 1 (25 [83%]); variable, E-cadherin and CK20 (17 [57%] each), MUC2 and MUC5AC (15 [50%] each), MUC1 (5 [17%]); negative, ER (0 [0%]); and (3) colon: frequent, MUC2 (9 [100%]), CDX2 and MUC5AC (8 [89%] each); infrequent or negative, MUC1 (3 [33%]), Hep Par 1 (2 [22%]), ER (0 [0%]). Immunohistochemical staining distinguished breast from gastric SRCC (ER, MUC1, Hep Par 1, CDX2) and colon SRCC (ER, CDX2, MUC2, and MUC5AC). Gastric and colon SRCCs showed a similar staining pattern for antibodies tested except for Hep Par 1 and CDX2 (gastric, 83% Hep Par 1 positivity and heterogeneous, weak, patchy CDX2 nuclear staining; colon, 22% Hep Par 1 positivity and homogeneous, strong, diffuse CDX2 nuclear staining). About half of the cases of gastric SRCC expressed MUC2 and MUC5AC, whereas virtually all cases of colon SRCC expressed them.
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developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands i stomach a relationship to gastric carcinoma
Journal of Histochemistry and Cytochemistry, 2000Co-Authors: Marie-pierre Buisine, Nicole Porchet, Jean-pierre Aubert, Mariechristine Copin, L Devisme, V Maunoury, Elisabeth Deschodt, Bernard GosselinAbstract:Studies were undertaken to provide information regarding cell-specific expression of mucin genes in stomach and their relation to developmental and neoplastic patterns of epithelial cytodifferentiation. In situ hybridization was used to study mRNA expression of eight mucin genes (MUC1-4, MUC5AC, MUC5B, MUC6, MUC7) in stomach of 13 human embryos and fetuses (8-27 weeks' gestation), comparing these with normal, metaplastic, and neoplastic adult tissues. These investigations have demonstrated that MUC1, MUC4, MUC5AC, MUC5B, and MUC6 are already expressed in the embryonic stomach at 8 weeks of gestation. MUC3 mRNA expression can be observed from 10.5 weeks of gestation. MUC2 is expressed at later stages, concomitant with mucous gland cytodifferentiation. Normal adult stomach is characterized by strong expression of MUC1, MUC5AC, and MUC6, less prominent MUC2, and sporadic MUC3 and MUC4, without MUC5B and MUC7. Intestinal metaplasia is characterized by an intestinal-type pattern with MUC2 and MUC3 mRNA expression. Gastric carcinomas exhibit altered mucin gene expression patterns with disappearance of MUC5AC and MUC6 mRNAs in some tumor glands, abnormal expression of MUC2, and reappearance of MUC5B mRNAs. In conclusion, we have observed that patterns of mucin gene expression in embryonic and fetal stomach could show similarities with some gastric carcinomas in adults. Differences in mucin gene expression in developmental, metaplastic, and neoplastic stomach compared to normal adult stomach suggest a possible regulatory role for their products in gastric epithelial cell proliferation and differentiation.
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altered expression of MUC2 muc4 and muc5 mucin genes in pancreas tissues and cancer cell lines
Gastroenterology, 1994Co-Authors: Cristina Balague, Nicole Porchet, Jean-pierre Aubert, Young S. Kim, Gemma Gambus, Cristina Carrato, Francisco X RealAbstract:Abstract Background/Aims: Neoplastic transformation of epithelial cells is commonly associated with altered synthesis and structure of mucin glycoproteins. The aim of the study was to determine if altered mucin gene expression takes place in pancreas cancer. Methods: To examine mucin gene expression in normal pancreas and pancreas cancer, antibodies detecting the MUC1, MUC2, MUC5B, and MUC5C apomucins were used in immunohistochemical techniques and complementary DNA probes specific for the MUC1-MUC5 genes were used in Northern blots. Results: MUC1 is the major apomucin expressed in normal pancreas, whereas MUC2-MUC5 are weakly expressed or undetectable. In pancreas cancer tissues and cell lines, increased expression of MUC2, MUC4, and MUC5C is shown. The cytoplasmic expression of MUC2 and MUC5C in tumor cells suggests that these apomucins are underglycosylated and abnormally compartmentalized. Conclusions: Enhanced expression of MUC2, MUC4, and MUC5C genes is a frequent event in pancreas cancer and may contribute to the alterations in the biochemical structure of pancreas cancer mucins.