| Background and objectiveGastric carcinoma is one of the commonest malignant tumors in our country. The carcinogenesis and development are related to many factors and are the result of a multiple-steps effect. In WHO Classification (2000), the gastric signet-ring cell carcinoma is defined as the carcinoma in which more than 50% of the tumor consists of isolated or small groups of malignant cells containing intracytoplasmic mucin. The signet-ring cell carcinoma can be divided into five types based on the cell morphology: classical type(type I), histiocyte-like type (type II), eosinophilic cell type(type III), small cell type (type IV), anaplastic cell type (type V). The gastric signet-ring cell carcinoma usually occurs in people relative young and shows a characteristic of high malignancy: stronger aggressive and progressive ability. The therapeutic efficacy and prognosis are relatively poor. It is indicated in some researches that the carcinogenesis and development of the tumor are related to the expression of the mucins. The cells in the gastric signet-ring cell carcinoma contain mucins. The relationships between the expression of the mucin and the biological behaviour of the tumor need further studies and discussions.Mucin (MUC) is a kind of macromolecule glycoprotein, including many different kinds of structures. It is secreted by many kinds of epithelial cells and is the main component of the mucinous products. Normally, the MUCs universally distribute in the gastrointestinal tract, respiratory tract, the genital tract and so on. The genes of MUC2, MUC5AC and MUC6 locate in 11p15.5. Physiologically, the MUC2 protein is only expressed in intestinal mucosa, which is also called intestinal type mucin; the MUC5AC and MUC6 proteins are only expressed in gastric mucosa, which are called gastric type mucins. The recent researches indicate that the gastric carcinomas express different types of micins, such as intestinal type carcinoma (expressing intestinal type mucin only, type I), gastric type carcinoma (expressing gastric type mucin only, type G), gastric and intestinal type carcinoma (expressing both intestinal type and gastric type of mucins, type GI) and uncalssfied type carcinoma (not expressing any mucins, type U), have different biological features. The researches about the expressions of the mucins in the gastric signet-ring cell carcinoma, including the relationships between the mucin expression and the cell morphologic types and the biological behaviors, are seldom reported in domestic and oversea literatures.This study detected the expressions of MUC2, MUC5AC and MUC6 proteins in the gastric signet-ring cell carcinoma and non-neoplastic gastric mucosa by immunohistochemical staining, and detected also the MUC2 mRNA in non-neoplastic gastric mucosa and gastric signet-ring cell carcinoma by in situ hybridization. The aim is to discuss the significance of the expressions and combining expressions of MUC2, MUC5AC and MUC6.Materials and methods1. Samples: The paraffin blots of 68 cases of gastric signet-ring cell carcinoma were collected from the archival surgical specimens of the Pathological Department of the First Affiliated Hospital of Zhengzhou University between 2002 January to 2004 December. Every case contains non-neoplastic gastric mucosa as a control. The patients had no history of the chemotherapy, radiotherapy and/or immunotherapy. According to the site, the 68 samples can be divided into 30 cases of cardia, 12 cases of fundus/corpus and 26 cases of antrum/pylorus; according to the morphology of the tumor cell, the samples can be divided into 29 cases of type I,18 cases of type II, 12 cases of type III, 5cases of type IV and 4 cases of type V. 2. Methods: The expressions of MUC2, MUC5AC and MUC6 protein in 68 cases of gastric signet-ring cell carcinoma and the corresponding non-neoplastic gastric mucosa were detected by immunohistochemical staining and the MUC2 mRNA in the carcinoma and the corresponding non-neoplastic gastric mucosa were also detected by in situ hybridization.3. Statistic analysis: All the data were analyzed by SPSS 10.0 statistical software package, including Chi-square and Fisher exact test and Spearman correlation analysis. The accepted level of significance was a =0.05. All p-values presented are two-sides.Results1. The positive rate of MUC2 protein expression is 0% in non-neoplastic gastric mucosa and 29.4% in gastric signet-ring cell carcinoma, there is significant difference between the two groups (P<0.05) . The positive rate of MUC2 protein expression is 36% in the male patients and 11.1% in female patients, there is significant difference between two groups (P<0.05) . The positive rate of MUC2 protein expression is 45.5% in patients without lymph node metastasis and 21.7% patients with lymph node metastasis, there is significant difference between the two groups (P<0.05). There is significant correlation between expression of MUC2 and lymph node metastasis in gastric signet-ring cell carcinomas (P<0.05) , r s=-0.312 and r s=-0.281.About the ages of onset, the locations, the tumor sizes, venous invasion, perineural invasion, the depths of infiltration, TNM stages or the cell morphologic types, none significant difference is found between the different parameters in any of the groups (P>0.05) .2. The positive rate of MUC2 mRNA is 0% in non-neoplastic gastric mucosa and 60.3% in gastric signet-ring cell carcinoma, , there is significant difference between the two groups (P<0.05) .About the genders, ages of onset, the locations, the tumor sizes, lymph node metastasis, venous invasion, perineural invasion, the depths of infiltration, TNM stages or the cell morphologic types, none significant difference is found between the different parameters in any of the groups (P>0.05) . There is no significant correlation between the expression of MUC2 protein and MUC2 mRNA (P>0.05) .3. The positive rate of MUC5AC protein expression is 92.6% in non-neoplastic gastric mucosa and 64.7% in signet-ring cell carcinoma (64.7%), there is significant difference between two groups (P<0.05) . The positive rate of MUC5AC protein expression is 74.5% in tumors≤5cm in the longest dimension and 42.9% in tumors >5cm in the longest dimension, there is significant difference between two groups(P<0.05). The positive rate of MUC5AC protein expression is 92.3% in tumors with T2 stage infiltration depth and 58.2% in tumors with T3 stage, there is significant difference between two groups (P<0.05) . There is significant correlation between expression of MUC5AC and tumors dimension , stage infiltration depth in gastric signet-ring cell carcinomas (P<0.05) , rs=-0.306 and rs=-0.281 respectively. About the genders, ages of onset, the locations, lymph node metastasis, venous invasion, perineural invasion, TNM stages or the cell morphologic types, none significant difference is found between the different parameters in any of the groups(P>0.05) .4. The positive rate of MUC6 protein expression is 88.2% in non-neoplastic gastric mucosa and 39.7% in gastric signet-ring cell carcinoma, there is significant difference between two groups (P<0.05) . The positive rate of MUC6 protein expression is 61.1% in female patients and 32% in male patients, there is significant difference between two groups (P<0.05) . The positive rate of MUC6 protein expression is 58.3% in tumors of fundus/corpus gastricum, 50% in tumors of antrum/pylorus and 23.3% in tumors of cardia, there is significant difference between the tumors of cardia and the tumors of fundus/corpus or the tumors of antrum/pylorus(P<0.05) . About ages of onset, the tumor sizes, lymph node metastasis, venous invasion, perineural invasion, the depths of infiltration, TNM stages or the cell morphologic types, none significant difference is found between the different parameters in any of the groups (P >0.05) .5. In type I signet-ring cell carcinoma, the expression rates of MUC2, MUC5AC and MUC6 are 41.4%, 62.1% and 31% respectively, the expression of MUC5AC is significantly higher than that of MUC6 (P<0.05) .In type II signet-ring cell carcinoma, there are no significant differences between the expressions of MUC2(27.8%) , MUC5AC(66.7%) and MUC6(44.4%), but the expressions between MUC5AC and MUC2 are significant different (P<0.05) . In type III carcinoma, the expression of MUC2 (16.7%) is lower than MUC5AC (50%) and MUC6 (33.3%) , but the difference is not significant statistically. In type IV carcinoma, the expression of MUC2 (0%) is significantly lower than that of MUC5AC (100%) and MUC6(80%)(P<0.05) .There is no significant difference between expressions of MUC2(25%), MUC5AC(72%)and MUC6(50%) in type V signet-ring cell carcinom (P>0.05) .6. To the associated expressions, there are no significant differences between the so called 4 types of gastric signet-ring cell carcinomas within any of the following aspects: gender, age of onset, tumor size, location, lymph nod metastasis, venous invasion, perineural invasion, infiltration depth ,TNM stage and cell types (P>0.05) .7. There is no significant correlation between expression of MUC2 MUC5AC and MUC6 protein (P>0.05) . The distributions are significantly different between different tumor cell types (P<0.05). In cardia, there are significantly more type III signet-ring cell carcinomas(83.3%) than type II (48.3%), type IV(27.8%) and V (0%).Conclutions1. The higher expression of MUC2 protein and MUC2 mRNA, and lower expression of MUC5AC and MUC6 in gastric signet-ring cell carcinoma may be related to the carcinogenesis of gastric signet-ring cell carcinoma. There is no significant correlation between expression of MUC2 protein and MUC2 mRNA, the higher expression of MUC2 protein may be related partly to the up-regulation of protein translation or the enhancement of protein stability.2. The expression of MUC2 is lower in the lymph node metastasis cases, maybe, indicating an inverse relation between the expression and the lymph node metastasis. The expression of MUC5AC may be inversely related to the tumor size and infiltration depth. The lower expression of MUC6 in cardiac signet-ring cell carcinoma, maybe, indicates the different differentiations of the tumors in different location. 3. There is no significant correlation between expression of MUC2 MUC5AC and MUC6 protein in gastric signet-ring cell carcinomas.4. The subtypes of the gastric signet-ring cell carcinoma show some differences in the expression of the mucins and the distributions, which may indicate that some of the subtypes represent different cytological differentiations. |
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