| Background: Serrated lesions were a series of correlation lesions being gradually recognized in recent 20 years. These lesions were characterized by glands with serrated glandular structure in histology manifestation. Now the studies of serrated lesions were mainly in colon and rectum at home and abroad. Known colorectal serrated lesions with significant heterogeneity and specific molecular changes showed a continuous pedigree. It has been postulated that about 10-15% of sporadic CRCs would have their origin in serrated lesions. Furthermore, serrated glandular structure (SGS) also could be seen in some gastric mucosal lesions in recent years were reported in succession. But it is still lack of systematic and comprehensive observations and studies on the SGS in gastric mucosal lesions. In view of it,this study was divided into two parts.Part I The detection and morphological characteristics of serrated glandular structure in different gastric mucosal lesions.Objective:To observe the SGS in different gastric mucosal lesions and summarize their histopathological features.Methods: During the period between October 1996 and March 2009, a total 820 cases of biopsy specimens which were diagnosed as local protuberant lesions by endoscopic examination at the Second Hospital of Hebei Medical University were collected, and except malignant tumors, stromal tumors and dysplasia by pathological diagnosis. At the same time, 147 cases of gastric adenocarcinoma surgical specimens were selected during the period between March 2007 and March 2009. HE staining sections of all specimens were observed. All cases diagnosed by criterias according to the Chinese Medical Association "Clinical Practice Guidelines ? Pathology volumes".Gastric adenocarcinoma samples were divided into well-differentiated group (including high, medium differentiated adenocarcinoma, papillary adenocarcinoma) and low-differentiated group (including low differentiated adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma). The cancerous tissues and the non-cancerous tissues were observed in mucosa adjacent to the gastric adenocarcinomous within 0.5 cm (after referred to as pericancerous mucosa). The experimental data were analyzed with Chi-square test with statistics software of SPSS13.0 edition, P<0.05 had statistically significance.Results:Of the 820 biopsy specimens, 289 were gastric polyps, 13 gastric adenomas, and the remaining 518 were inflammation.Among 289 cases of gastric polyps, including hyperplastic polyps 167 cases, 98 cases of fundic gland polyps, 5 cases of inflammatory fibroid polyps, 19 cases of mixed polyps which were coexistence of hyperplastic polyp and fundic gland polyp or inflammatory fibroid polyp.Histological observation found that one case of the 13 gastric adenomas with gastic adenocarcinoma component in other sub-site, 4 cases of gastric adenomas with hyperplastic polyp component in other sub-site of the stomach.In gastric adenocarcinoma surgical specimens, well differentiated carcinomas and poorly differentiated carcinomas were 42 cases and 107 cases, respectively.Among them, one of 107 poorly differentiated invasive carcinoma with a gastric adenoma adjacent to carcinoma tissues.1. The detection of SGS in different gastric mucosal lesionsAmong 967 cases of benign and malignant gastric mucosal lesions, 268 cases could be observed the SGS which always presented a focal distribution. Among them, polyps were 118 cases, inflammation were 92 cases, gastric adenocarcinoma were 58 cases.In biopsy specimens, 13 cases of gastric adenoma could not be detected the SGS. Otherwise, the SGS could be observed in the gastric adenoma which had a coexisting gastric adenocarcinoma was previous descripted.In biopsy specimens, the detection rates of SGS were 17.76% of 518 inflammation and 40.83% of 289 gastric polyps, respectively.The SGS could be observed in 106 cases of hyperplastic polyps (63.47%, 106/167). Fundic gland polyps and inflammatory fibroid polyps could not be detected the SGS. The detection rates of SGS in different gastric polyps were significant difference (P<0.05). 3 cases of hyperplastic polyps with SGS concurred with gastric carcinoma in other parts of stomach.The detection of SGS in gastric polyps was related to hyperplastic polyp. Among gastric polyps with SGS, hyperplastic polyps accounted for 89.83% (106/118), 10.17%(12/118)were mixed polyps,and both distributed in the region of hyperplastic polyp. The detection rates of hyperplastic polyps and mixed polyps had no significant difference (P>0.05). In addition, four of the 13 adenomas with hyperplastic polyps, three of them could be detected the SGS.The detection rate of SGS in the pericancerous mucosa was 39.46% (58/147), and gastric adenocarcinomas with SGS were mostly poorly differentiated adenocarcinoma (70.69%, 41/58), 17 cases (28.31%, 17/58) were well-differentiated adenocarcinoma. Statistics showed that the detection rates of SGS in the pericancerous and polyps had no significant difference (P>0.05), the detection rates of SGS in both lesions were significantly higher than that of inflammation (P <0.05).In addition, there were 19 cases of gastric carcinomas could detected cancerous SGS in muscularis mucosa or muscularis. This study observed that the SGS could be detected in some gastric mucosal lesions such as gastric mucosal inflammation, hyperplastic polyps, adenoma, pericancerous mucosa, gastric adenocarcinomas and so on.2. The distribution of SGS in different gastric mucosal lesionsIn this study, involving the occurred sub-site of gastric mucosal inflammation, 55.98% (290/518)of inflammation was occurred in the antrum, followed by fundus/body (31.85%, 165/518), the least in the cardia (12.16%, 63/518).In inflammation, the detection rate of SGS in cardia was highest, reached 25.4% (16/63), followed by antrum (20.34%, 59/290), the detection rate of SGS in the fundus/body was significantly decreased (10.3%, 17/165) (P<0.05).In different gastric polyps, hyperplastic polyps with higher detection rate of SGS. The detection rates of SGS in different sites of stomach were 63.08% (41/65), 68.18% (45/66) and 55.56% (20/36) in the antrum, the fundus/body and the cardia, respectively. The distribution of SGS in hyperplastic polyps had no significant difference (P>0.05).In this study, gastric adenocarcinomas were mainly occurred in the cardia (59.86%, 88/147), followed by the antrum (38.78%, 57/147), gastric body cancer only 2 cases. The previously described case of gastric adenocarcinoma with a gastric adenoma was located in the antrum.There was no significant difference in the detection rates of SGS in the pericancerous mucosa of cardiac and antral adenocarcinomas (36.36% vs 42.1%, P> 0.05). 2 cases of adenocarcinoma in gastric body could be observed the SGS. Further analysis showed that cases of gastric carcinoma with SGS in pericancerous mucosa were more common in poorly differentiated group. There was no significant difference in the differentiation of cardiac and antral adenocarcinoma (71.88% vs 70.83%, P> 0.05).3. The histopathological characteristics and the detection of SGS in different gastric mucosal lesionsThe SGS was composed of hyperplastic epithelial cells in gastric mucosa by observation. Some hyperplastic glandular epithelial cells with serration were observed in the gastric pits and the extended spot of pits. Inherent glands around the SGS were existed, but decreased in number, the glandular structure and cell morphology were unchanged. The SGS could be observed in the center of hyperplastic polyps.The serrated glandular epithelial cells had more or less changes in the cytoplasm or nucleus compared with the normal gastric surface epithelial cells. According to the morphological changes of epithelial cells, the SGS could be divided into three types. Type I, the serrated glandular epithelium cells with crowded arrangement and protruding to the cavity, could formed the small seamless papillae, had no obvious abnormalities of nuclear morphology, nucleus at the base, and cells riched in cytoplasm. Type III, these serrated glands are lined by epithelium cells with varying grades of dysplasia, cells polar disorder, eosinophilic increased in cytoplasm was occasionally observed , and partial pseudostratified nuclei at higher magnification. Except for I-type and III-type, the remaining SGS were type II. The epithelial cells of II-type SGS were closely arranged, the nuclei were enlarged and elongated, caryoplasm ratio was obviously increased, focal nuclear atypia, partial pseudostratified, nucleoli could be seen.All types of SGS with intestinal metaplasia could be observed.The I-type SGS in hyperplastic polyps were particularly riched in cytoplasm.The existed patterns of SGS in different gastric mucosal lesions have varied. In benign lesions, the main existed forms of SGS were mixed such as I type, or I & II type. The detection rate of III-type was significantly increased in the pericancerous mucosa. Otherwise, the III-type SGS could be observed in the previously described case of gastric adenoma which occurred in pericancerous mucosa.To facilitate the statistics, the two or three types of SGS appeared at the same time,the high-level classification shall prevailed. I-type SGS was more common in gastric mucosal inflammation, at most 50%, followed by II-type (44.57%), only 5.43% was III-type, three cases occurred in the antrum, two cases in the gastric fundus/body.The proportion of II-type SGS in hyperplastic polyps was higher (54.72%), I-type was 44.34%, only one case (5.43%) of hyperplastic polyps with III-type, occurred in the gastric body.. The proportion of type III was increased significantly (37.93%) in pericancerous mucosa. The proportion of I and II Type were 27.59% and 34.48%, respectively. The detection rates were significant difference between different gastric mucosal lesions and between three types of SGS (P<0.05).Statistical analysis showed that the detection of different types SGS in inflammation and hyperplastic polyps had no significant difference (P>0.05), there were significant different in the detection of different types SGS between benign and malignant mucosal lesions (P<0.05).Part II The immunohistochemical observation of different types of serrated glandular structure in gastric mucosal lesionsObjective: To investigate the proliferation and apoptosis characteristics of serrated glandular epithelial and the infection of H. pylori in different gastric mucosal lesions with SGS.Methods: On the basis of observation in the first part, 129 cases of the gastric mucosa lesions with SGS were selected (including 23 cases of inflammation, 57 cases of hyperplastic polyps, 49 cases of gastric adenocarcinoma).Those cases with III-type SGS in benign gastric lesions were too little to selected in this part. And cases with intestinal metaplasia in different gastric mucosal lesions were also eliminated.The same as the first part, the two or three types of SGS appeared at the same time,the high-level classification shall prevailed. There were 20 archived paraffin-embedded specimens result from trauma or resection of the stomach due to duodenal ulcer used as controls. S-P immunohistochemical methods were used to observe the expression of Ki-67, Bcl-2, p53 in SGS and the infection of H. Pylori in different gastric mucosal lesions with SGS. The experimental datas were analyzed with one-way ANOVA, non-parametric rank sum test and Chi-square test with statistics software of SPSS13.0 edition, P<0.05 had statistically significance.Results:1. The expression of Ki-67 in SGS of different gastric mucosal lesionsThe positive immunoreaction of Ki-67 was located in the nucleus. Positive cells were confined to the bottom of gastric pits and the neck of gastric glands in normal gastric mucosa, the labeling index of Ki-67 was 18.05±8.93. The labeling index of Ki-67 I, II type SGS in inflammation were 5.08±5.02 and 45.6±36.36, respectively. The labeling index of Ki-67I, II type in hyperplastic polyps were 7.45±14.78 and 51.33±25.31, respectively. In pericancerous mucosa, the labeling index of Ki-67 in I, II and III type SGS were 5.81±11.18, 30.28±17.76 and 59.93±25.46, respectively.Statistics results showed that the labeling index of Ki-67 in I-type SGS in different gastric mucosal lesions was significantly lower than that of normal control group (P<0.05), The labeling index of Ki-67 in II-type SGS was significantly higher as compared with that of I-type SGS (P<0.05); The labeling index of Ki-67 in I, II and III type SGS of the pericancerous mucosa increased by degrees, there were significant difference between three types(P<0.05). The labeling index of Ki-67 in I or II type SGS had no significant difference between different gastric mucosal lesions (P>0.05).2. The expression of Bcl-2 in SGS of different gastric mucosal lesionsThe positive reaction of Bcl-2 was located in cytoplasm. The negative expression of Bcl-2 in surface epithelium of 20 cases normal contors. lymphoid follicles mantle cells and mature small lymphocytes. 1 case of the 20 was expressed in Inherent glandular epithelium.In different gastric mucosal lesions, Bcl-2 mainly showed weakly positive, minority showed moderate expression on expression in SGS, there was no strong positive.In inflammation, the positive expression of Bcl-2 in I and II type SGS were 7cases (7/13), 4 cases (4/10), respectively, there was no significant difference between two types (P>0.05). In hyperplastic polyps, the positive expression of Bcl-2 in I and II type SGS were 5 cases (5/11), 26 cases (26/46), respectively, there was also no significant difference between two types (P>0.05).Further analysis showed that the positive expression Bcl-2 in I and II type SGS of benign lesions had no significant difference (P>0.05).In pericancerous mucosa, there was no positive expression of Bcl-2 in I type SGS, the positive expression in II and III -type SGS were 3 cases (3/18), and 1 case (1/14), respectively. The positive expression of Bcl-2 in different types of SGS had no significant difference (P>0.05). The positive expression of Bcl-2 in SGS of pericancerous mucosa had significantly lower than those of inflammation and hyperplastic polyps (P<0.05). 3. The expression of p53 in SGS of different gastric mucosal lesionsPositive immunoreaction of p53 was located in the nucleus. The positive expression of p53 in I-type SGS in three kinds gastric mucosal lesions and normal control group were not seen.There were 2 cases of inflammation, 10 cases of hyperplastic polyps, and 5 cases of pericancerous mucosa with II-type SGS showed p53 positive expression (2/10, 10/46, 5/18).The positive expression of p53 in II -type SGS of different mucosal lesions had no significant difference (P>0.05).The positive expression of p53 in III-Type SGS (11/15) was significantly increased as compared with that of II-type SGS in pericancerous mucosa (P<0.05).The positive expression of p53 in three types SGS had significant difference (P<0.05).4. The infection rates of H.pylori in different gastric mucosal lesions with SGSThe infection rates of H.pylori in inflammation with I and II type SGS were 38.46% and 20%, respectively, two groups showed no significant difference (P>0.05). The infection rates of H.pylori in hyperplastic polyps with I, II type SGS were 18.18% and 30.43%, respectively, the two groups had no significant difference (P>0.05). The infection rates of H.pylori in pericancerous mucosa with I, II ,III type SGS were 12.5%, 33.33% and 6.67%,respectively, no significant differences among the three groups (P>0.05). Statistical results showed that the three kinds of gastric mucosal lesions with SGS were associated with a certain infection rate of H.pylori. The infection rates of H.Pylori had no significant differences between different mucosal lesions with SGS (P>0.05).Conclusion:1 The SGS could be detected in some gastric mucosal lesions such as inflammation, hyperplastic polyps, adenomas, pericancerous mucosa and gastric adenocarcinomas.2 The detection rate of SGS in gastric mucosal inflammation was 17.76%; of which were more detected in the cardia, followed by antrum; The detection rate of SGS in gastric fundus/body were significantly lower than those in cardia and antrum.3 The detection rate of SGS in gastric polyps was 40.83%, and the SGS was related to hyperplastic polyps. The detection rates of SGS in hyperplastic polyps of different parts had no significant difference. It is prompted that the SGS might be the histological feature of hyperplastic polyps.4 The detection rate of SGS in pericancerous mucosa was 39.46%, there were no significant difference in different parts. The majority of gastric adenocarcinomas belong to poorly differentiated group. It is suggested that the SGS might be related to poorly differentiated gastric adenocarcinoma.5 Observed in this study, according to the morphological changes of epithelial cells, the SGS could be divided into three types. The existence patterns of SGS in different gastric mucosal lesions has varied. The common forms of SGS in benign lesions were I or I / II-type.6 The III-type SGS were increased significantly in pericancerous mucosa as compared to other benign lesions.The labeling index of Ki-67and the positive expression of p53 in III-type SGS were significantly ascended, the positive expression of Bcl-2 was significantly reduced, All of above suggested that the occurrence of some gastric adenocarcinomas had correlation with the III-type SGS.7 Different gastric mucosal lesions with SGS had a certain percentage of H.pylori infections, the infection rate of H.pylori had no significant difference between different lesions, it is suggested that H.pylori might be a pathogenic factor for the formation of SGS.
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