Istological types in total. Among the 197 lesions, there were 15 lesions of papillary adenoBTZ043 carcinoma (pap) (Figs. 2A ), 39 of well differentiated tubular adenocarcinoma (tub1) (Figs. 2E ), 52 of moderately differentiated tubular adenocarcinoma (tub2) (Figs. 2I ), 6 of mucinous carcinomas (muc) (Figs. 2M ), 8 of solid type poorly differentiated adenocarcinoma (por1) (Figs. 2Q ), 47 of non-solid type poorly differentiated adenocarcinoma (por2) (Figs. 2U ) and 30 of signet-ring 
cell carcinoma (sig) (Figs. 2Y-b), based on the context of common histological classification of gastric cancer in JCGC [16]. According to the context in the WHO classification of tumours of the stomach [17] as well as that in JCGC [16], pap and tub1 were classified into “well-differentiated adenocarcinoma”, and por1 and por2 were classified into “poorly-differentiated adenocarcinoma”. The data of the expression rate of MUC4/ 8G7, MUC4/1G8 and MUC1/DF3 were summarized in Figure 3. The detailed number and percentage of positively stained neoplastic cells using the scoring system were summarized in Table S1. Expression profile of MUC4/8G7. Among the 197 adenocarcinoma lesions, MUC4/8G7 was expressed in 83 lesions (42 ). MUC4/8G7 showed a significantly higher rate of the positive expression ( 5 of carcinoma cells stained) in well differentiated types (pap+tub1: 70 , 38/54) than that in poorly differentiated types (por1+por2: 18 , 10/55) (P,0.0001) (Fig. 3A, HIV-RT inhibitor 1 site arrows).MUC4 and MUC1 Expression in Early Gastric CancersTable 3. Clinicopathological studies using anti-MUC4 monoclonal antibodies, 8G7 and 1G8.Organ Oral cavity Upper aerodigestive tract Salivary gland Salivary gland Salivary gland Thyroid ThyroidCarcinoma type Squamous cell carcinoma Squamous cell carcinoma Mucoepidermoid carcinoma Mucoepidermoid carcinoma Mucoepidermoid carcinoma Papillary carcinoma Papillary carcinomaUsed Antibody 8G7 1G8 1G8 1G8 Rabbit polyclonal (Gut 2000 47:349) 1G8 1GCorrelation of MUC4 expression with outcome Poor Better Better No correlation Better No expression of MUC4/1G8 Correlation with small tumor size and microcarcinoma subtype, No comment for outcome Poor Better Better No correlation No association with tumor type, stage or with the degree of differetiation, No comment for outcome Poor Poor Poor Poor Poor No correlationReference Hamada (2012) Weed (2004) Weed (2004) Handra-Luca (2005) Alos (2005) Baek (2007) Nam (2011)Ref. No [9] [28] [27] [20] [19] [25] [23]Lung Lung Lung Breast StomachSmall sized adenocarcinoma Non mall cell lung carcinoma Non mall cell lung carcinoma(NSCLC) Adenocarcinoma Adenocarcinoma8G7 1G8 (Zymed) 1G8 1G8 8GTsutsumida (2007) Kwon (2007) Jeon (2010) Rakha (2005) Senapati (2008)[13] [29] [30] [21] [18]Bile duct Bile duct Pancreas Pancreas Colon Ovary ProstateIntrahepatic cholangiocarcinoma-mass forming type Extrahepatic bile duct carcinoma Invasive ductal carcinoma Pancreatobiliary adenocarcinomas Colorectal adenocarcinoma Serous, mucinous, endometrioid and clear cell carcinoma Prostate cancer8G7 8G7 8G7 1G8 8G7 8G7 8GShibahara (2004) Tamada (2006) Saitou (2005) Westgaard (2009) Shanmugam (2010) Chauhan (2006)[10] [11] [12] [31] [26] [22] [24]Down regulation in prostate Singh (2006) cancer tissues, No comment for outcomedoi:10.1371/journal.pone.0049251.tMUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells of pap (Fig. 2B), tub1 (Fig. 2F) and tub2 (Fig. 2J), in the cases with positive expression. Expression profile of MUC4/1G8. Among the.Istological types in total. Among the 197 lesions, there were 15 lesions of papillary adenocarcinoma (pap) (Figs. 2A ), 39 of well differentiated tubular adenocarcinoma (tub1) (Figs. 2E ), 52 of moderately differentiated tubular adenocarcinoma (tub2) (Figs. 2I ), 6 of mucinous carcinomas (muc) (Figs. 2M ), 8 of solid type poorly differentiated adenocarcinoma (por1) (Figs. 2Q ), 47 of non-solid type poorly differentiated adenocarcinoma (por2) (Figs. 2U ) and 30 of signet-ring cell carcinoma (sig) (Figs. 2Y-b), based on the context of common histological classification of gastric cancer in JCGC [16]. According to the context in the WHO classification of tumours of the stomach [17] as well as that in JCGC [16], pap and tub1 were classified into “well-differentiated adenocarcinoma”, and por1 and por2 were classified into “poorly-differentiated adenocarcinoma”. The data of the expression rate of MUC4/ 8G7, MUC4/1G8 and MUC1/DF3 were summarized in Figure 3. The detailed number and percentage of positively stained neoplastic cells using the scoring system were summarized in Table S1. Expression profile of MUC4/8G7. Among the 197 adenocarcinoma lesions, MUC4/8G7 was expressed in 83 lesions (42 ). MUC4/8G7 showed a significantly higher rate of the positive expression ( 5 of carcinoma cells stained) in well differentiated types (pap+tub1: 70 , 38/54) than that in poorly differentiated types (por1+por2: 18 , 10/55) (P,0.0001) (Fig. 3A, arrows).MUC4 and MUC1 Expression in Early Gastric CancersTable 3. Clinicopathological studies using anti-MUC4 monoclonal antibodies, 8G7 and 1G8.Organ Oral cavity Upper aerodigestive tract Salivary gland Salivary gland Salivary gland Thyroid ThyroidCarcinoma type Squamous cell carcinoma Squamous cell carcinoma Mucoepidermoid carcinoma Mucoepidermoid carcinoma Mucoepidermoid carcinoma Papillary carcinoma Papillary carcinomaUsed Antibody 8G7 1G8 1G8 1G8 Rabbit polyclonal (Gut 2000 47:349) 1G8 1GCorrelation of MUC4 expression with outcome Poor Better Better No correlation Better No expression of MUC4/1G8 Correlation with small tumor size and microcarcinoma subtype, No comment for outcome Poor Better Better No correlation No association with tumor type, stage or with the degree of differetiation, No comment for outcome Poor Poor Poor Poor Poor No correlationReference Hamada (2012) Weed (2004) Weed (2004) Handra-Luca (2005) Alos (2005) Baek (2007) Nam (2011)Ref. No [9] [28] [27] [20] [19] [25] [23]Lung Lung Lung Breast StomachSmall sized adenocarcinoma Non mall cell lung carcinoma Non mall cell lung carcinoma(NSCLC) Adenocarcinoma Adenocarcinoma8G7 1G8 (Zymed) 1G8 1G8 8GTsutsumida (2007) Kwon (2007) Jeon (2010) Rakha (2005) Senapati (2008)[13] [29] [30] [21] [18]Bile duct Bile duct Pancreas Pancreas Colon Ovary ProstateIntrahepatic cholangiocarcinoma-mass forming type Extrahepatic bile duct carcinoma Invasive ductal carcinoma Pancreatobiliary adenocarcinomas Colorectal adenocarcinoma Serous, mucinous, endometrioid and clear cell carcinoma Prostate cancer8G7 8G7 8G7 1G8 8G7 8G7 8GShibahara (2004) Tamada (2006) Saitou (2005) Westgaard (2009) Shanmugam (2010) Chauhan (2006)[10] [11] [12] [31] [26] [22] [24]Down regulation in prostate Singh (2006) cancer tissues, No comment for outcomedoi:10.1371/journal.pone.0049251.tMUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells of pap (Fig. 2B), tub1 (Fig. 2F) and tub2 (Fig. 2J), in the cases with positive expression. Expression profile of MUC4/1G8. Among the.