| Background Gastric epithelial dysplasia (GED) is a precancerous lesion of gastric cancer and has crucial clinical meanings. It is notoriously difficult sometimes to distinguish dysplasia from regenerative or metaplastic lesions. In addition, only small portion of cases will develop gastric cancer and the majority may regress or persist during long-term follow up. Therefore, it would be useful if we could find some adjuvent markers for helping identify dysplasia and even cases with high risk for cancer. Since the prevalence of H. pylori is relatively high in Chinese population, chronic atrophic gastritis with intestinal metaplasia (IM) is frequently seen. IM can be hyperprolifered and display cytoarchitectural atypia which often cause diagnostic difficulty. Yet, few studies have evaluated the prevalence, the morphologic and biologic characteristics of intestinal metaplasia with atypical hyperproliferation (IMAH), which classified into "indefinite for dysplasia" presently because of lack of knowing of its biologic nature. These are the questions we are going to answer in this research.Material and methods Searching data base from PUMCH for gastric biopies performed during2009and from2003through2007. In the first cohort, during whole year of2009,554biopsies with chronic atrophic gastritis and/or dysplasia were identified, we categorized the cases as either1) simple IM (SIM);2) IM with hyperplasia (IMH);3) IM with atypical hyperproliferation (IMAH) and4) gastric dysplasia (GED). The relationship between histologic subtypes and various clinicopathological features (i. e. sex, age, site, H. pylori status), histochemstry, mucin immunophenotypes (i.e. gastric, gastrointestinal, intestinal and small intestinal)and biologic characteristics (i. e. p53, ki-67index and AMACR) was evaluated. In the second cohort,151patients diagnosed as dysplasia and with follow-up biopsies or resection specimen were identified.44out of151patients had interval of follow-up longer than six months.83biopsies or resection specimen from20patients were finally enrolled to evaluate clinicopathological featuers, mucin phenotypes, biologic features and prognosis.Results The first cohort from2009biopsies comprised of424cases of SIM,93IMH,16IMAH, and21GED. IMAH had a prevalence of2.8%and similar to GED3.7%. There were no significant difference regarding to age and sex. Both of IMAH and GED were similar in body/fundus distribution (12.5%) and paucity of goblet cells (68.8%). IMAH and GED seem to share some biologic similarities but with a lower frequency of AMACR expression (25%vs.62%), p53expression (6.3%vs.47.6%) and increased Ki-67index on surface/pit and isthmus in IMAH. Alternatively, SIM and IMH did not differ statistically with regard to the various characteristics evaluated. The second cohort initially selected151patients with follow-up data. The mean age was60.3ranging from33-85years old. Male and female ratio was2.02:1.76.2%of cases were found in antrum, the rest were in body/fundus (23.8%).45%(68/151) patients were first diagnosed as low-grade dyplasia. Among patients with follow-up period longer than6months,78.8%(26/33) were regressed,12.1%(4/33) persisted, and9.1%(3/33) progressed.55%(83/151) patients were first diagnosed as high-grade dysplasia,59of whom performed EMR or surgical resection, and24of whom were follow-up closely. Among patients with follow-up period longer than6months,54.4%(6/11) were regressed,36.4%(4/11) persisted, and9.1%(1/11) progressed to adenocarcinoma.20patients were evaluated for further immunostains. Mucin phenotypes among patients whose lesions were regressed were gastrointestinal (5patients), small intestinal (2patients) or gastric subtype (1patient).2patients with first diagnosed as high-grade dysplasia and regressed to low-grade displayed small intestinal (1patient) and intestial subtyps (1patient). Among6patients with persistent dysplasia,3low-grade dysplasia cases showed small intestinal (2patients) and gastrointestinal (1patient) phenotype. One of the patients converted to gastric phenotype from small intestianl phenotype after46months follow-up. The phenotypes of3persistent high-grade dysplasia were gastric, gastrointestinal and small intestinal, respectively.3out of4progressed cases were converted to gastric phenotype from small intestinal (2patients) and gastrointestinal phenotype (1patient). p53overexpression were found in20%(2/10) regressed,16.7%(1/6) persistent and50%(2/4) progressed patients. AMACR positivity were20%(2/10),33.3%(2/6) and75%(3/4), respectively among three groups. MUC6ectopic exression were30%(3/10),33.3%(2/6) and50%(2/4)Conclusion (1)Gastric IM can be divided into2broad categories, that is IM without atypia, including SIM and IMH, and IM with atypia, i.e. IMAH.(2) We first reported the prevalence of IMAH among patients with chronic atrophic gastritis was2.9%, similar with the rate for dysplasia (3.8%). In addtion, the prevalence of dysplasia in Chinses population was slightly higher than western but much lower than what was expected previously.(3) Based on the characteristics of IMAH and in keeping with others, we confirm that this subtype could represent a preneoplastic lesion that should initiate endoscopic surveillance.(4) AMACR was positive in25%IMAH and the positivity rate increased with the progression of lesions. We assume that AMACR could be an early biomarker for gastric intraepithelial tumor.(5)Conbimed detection of p53,, ki-67index and MUC6ectopia may adjuvent for GED diagnosis.(6) Regarding to four mucin phenotypes, gastrointestinal phenotype may represent a transitional condition which is unstable and could further differentiate into small intestinal phenotype which represent a more mature stage, or become gastric or intestinal types which contain higher risk for cancer. |
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