Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus?

Dysplasia in Barrett esophagus has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a tumor suppressor role for CDX-2 in the metaplasia-dysplasia-carcinoma sequence. The phenotypic stability and role of CDX-2 in the neoplastic progression of different types of dysplasias have not been evaluated. Thirty-eight endoscopic mucosal resections with dysplasia and/or intramucosal carcinoma (IMC) arising in Barrett esophagus were evaluated for the expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2. The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had IMC and dysplasia, 8 had IMC only, and 7 had dysplasia only. Among dysplastic lesions, 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with dysplasia and adjacent IMC showed an identical immunophenotype of dysplasia and IMC comprising 16 gastric, 3 intestinal, and 1 mixed immunophenotype. Three cases showed discordance of dysplasia and IMC immunophenotype. These findings suggest that most Barrett-related IMC cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of carcinogenesis. CDX-2 showed gradual downregulation of expression during progression in adenomatous dysplasia but not in foveolar or hybrid dysplasia, supporting a tumor suppressor role, at least in the intestinal pathway. CDX-2 was also found to be expressed to a greater degree in intestinal metaplasia compared with nonintestinalized columnar metaplasia. Consistent with CDX-2 as a tumor suppressor, this suggests that nonintestinalized columnar metaplasia may be an unstable intermediate state at risk for neoplastic progression.     

Postatrophic hyperplasia of the prostate gland: a detailed analysis of its morphology in needle biopsy specimens.

Postatrophic hyperplasia is a histologic pattern showing atrophic and hyperplastic glands, sometimes with a small acinar configuration. Because distinction from small acinar carcinoma may be challenging, particularly in needle biopsy specimens, we studied 56 needle biopsy specimens containing 68 foci to ascertain the morphologic spectrum of postatrophic hyperplasia. All foci showed a distinct lobular small acinar proliferation with varying proportions of atrophic and hyperplastic glands. Gland size was typically variable, predominantly of small caliber but occasionally of intermediate to larger caliber. Round, oval, elongated, slitlike and stellate glands were seen. The nuclei were generally regular without hyperchromasia, with rare small nucleoli seen in 10 (15%) foci. The cytoplasm was variable, ranging from scant in atrophic glands to moderate or abundant and clear or occasionally eosinophilic in hyperplastic glands. An irregular internal gland contour was noted in glands with features of both atrophy and hyperplasia. Basal cells were apparent by light microscopy in most foci, although their distribution within foci and between foci varied. This finding was confirmed in all 26 cases studied with the high molecular weight cytokeratin immunohistochemical stain (34betaE12). Associated pathology included adenocarcinoma (12%), high-grade prostatic intraepithelial neoplasia (3%), atrophy distinct from foci of postatrophic hyperplasia (55%), and atypical adenomatous hyperplasia (2%). Adjunctive features of cancer were not seen in any of the foci of postatrophic hyperplasia. Familiarity with the histologic features of postatrophic hyperplasia will allow its confident separation from cancer, especially in limited biopsy material.     

The extrahepatic bile duct lesions in end-stage primary sclerosing cholangitis

We examined histologically the bile duct lesions from 53 patients with end-stage primary sclerosing cholangitis (PSC) and compared them with similar lesions found in 25 surgically excised carcinomas of the extrahepatic bile ducts not associated with PSC. Of the 53 cases of PSC, 50 bile ducts were obtained at liver transplantation, two common bile ducts were segmentally resected for almost complete obstruction, and the entire extrahepatic biliary tract of another case was obtained at autopsy. Twenty bile ducts from patients who died without evidence of biliary tract disease served as controls. A modest increase in the number of intramural glands (mild hyperplasia) was noted in 13 cases (24.5%) of PSC. A marked increase in the number of intramural glands (florid hyperplasia) was found in 14 cases (26.4%) of PSC. In one case of florid hyperplasia, there was perineural and intraneural invasion of benign hyperplastic glands, which still maintained their lobular pattern. All cases of florid hyperplasia of intramural glands were accompanied by extensive fibrosis and marked nerve proliferation. Three of 24 (12.5%) invasive adenocarcinomas of the extrahepatic bile ducts showed mild hyperplasia of intramural glands without excessive nerve proliferation. Four invasive adenocarcinomas and one in situ carcinoma of the extrahepatic bile ducts showed florid hyperplasia of intramural glands (16%). The hyperplastic intramural glands were p53 negative and had low proliferative activity as measured by the low MIB-1 labeling index. In contrast, both in situ and invasive carcinoma expressed p53 protein and had a high MIB-1 labeling index. Focal high-grade dysplasia was found in one case of PSC (1.8%) and a small invasive adenocarcinoma in another (1.8%). Hyperplasia of intramural glands of the extrahepatic bile ducts is a reactive process that lacks specificity and is part of the morphologic spectrum of end-stage PSC. The incidence of dysplasia in PSC is low. Small invasive adenocarcinomas may be incidentally found in end-stage PSC, and detecting their presence before liver transplantation may be impossible.     

Dysplasia of nonmetaplastic gastric mucosa. A proposal for its classification and its possible relationship to diffuse-type gastric carcinoma

In a review of 192 gastric resections, histological changes believed to represent dysplasia of nonmetaplastic gastric epithelium were observed. This paper presents a proposal for their classification. The main feature of this dysplasia is replacement of the differentiated cells lining the glands by undifferentiated cells with varying degrees of cytological abnormalities and cellular pleomorphism, but with absence of architectural glandular derangement. The classification is justified by cytokinetic and histologic observations in experimental gastric carcinogenesis and early human gastric carcinoma. The severity of the changes is graded, first, by the extent of involvement of the gland (crypt) as measured from the proliferative zone (PZ), and, second, by the degree of cytological abnormality. It utilizes a modification of the terminology of Riddell et al. (45) for dysplasia in inflammatory bowel disease wherein the term "dysplasia" denotes intraepithelial neoplasia. The changes are classified into (a) negative for dysplasia, (b) atypical, i.e., indefinite for dysplasia, and (c) positive for dysplasia. Changes negative for dysplasia are considered regenerative and consist of enlargement and vesicular transformation of the nucleus in the cells of the PZ and adjacent part of the crypt. Atypical changes consist of equivocal lesions difficult to classify as definitely regenerative or definitely dysplastic, and are hence called indefinite for dysplasia. They consist of loss of cytoplasmic differentiation of the cells lining the glands (i.e., mucus production and parietal and chief cell differentiation) with increased nuclear-cytoplasmic ratio and moderate cytological atypicality. Based on the extent of gland involvement, the group with atypical mucosa is subdivided into two categories--atypical, probably negative for dysplasia (AtN) and atypical, probably positive for dysplasia (AtP). Mucosa exhibiting unequivocal cytological features of neoplasia with cellular and nuclear pleomorphism is classified as positive for dysplasia (D). This is subdivided into low-grade and high-grade dysplasia, the latter representing carcinoma in situ. Glandular architecture remains undisturbed in all stages and the cells remain cuboidal, without transformation into intestinal-type cells. This type of dysplasia was found in a significantly higher number of diffuse-type carcinomas than in intestinal-type carcinomas. The previously well-recognized adenomatous or metaplastic dysplasia was significantly more prevalent in intestinal-type carcinoma than in diffuse-type.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hyperplastic polyps of the stomach: associations with histologic patterns of gastritis and gastric atrophy

Hyperplastic polyps are common gastric lesions characterized by hyperplastic foveolae with variable amounts of inflamed stroma. Their pathogenesis is unknown, but they have been reported to occur in association with various forms of chronic gastritis, particularly autoimmune gastritis and Helicobacter pylori gastritis. Comprehensive histologic evaluation of the background mucosal pathology in patients with hyperplastic polyps has not been previously performed. We studied 160 patients with gastric hyperplastic polyps and characterized endoscopic and histologic features of the polyps (i.e., location, multiplicity, and presence of dysplasia and adenocarcinoma) and the background gastric mucosa (i.e., intestinal metaplasia, dysplasia, carcinoma, and presence and classification of gastritis). Hyperplastic polyps were most common in the antrum (60%) and were multiple in 20% of patients. Focal intestinal metaplasia of the polyp was present in 16% and dysplasia in 4% of patients. Only one patient (0.6%) had adenocarcinoma within the polyp. Evaluation of the surrounding gastric mucosa showed at least focal intestinal metaplasia in 37% of patients, adenoma or low-grade flat epithelial dysplasia in 2%, and synchronous or metachronous adenocarcinoma in 6%. Eighty-five percent of patients had inflammatory mucosal pathology, most commonly active chronic H. pylori gastritis (25%), reactive or chemical gastropathy (21%), and metaplastic atrophic gastritis of the autoimmune (12%) or environmental (8%) type. These results indicate a strong association between various forms of gastritis and the development of hyperplastic polyps and further emphasize the importance of biopsy of the nonpolypoid gastric mucosa during endoscopic examination.     

Esophageal polypoid dysplasia of gastric foveolar phenotype with focal intramucosal carcinoma associated with Barrett's esophagus

We describe a rare case of esophageal polypoid dysplasia with gastric phenotype and focal intramucosal carcinoma associated with Barrett's esophagus. A 69-year-old man with a long history of gastroesophageal reflux disease was initially seen at an outside institution for evaluation of significant dysphagia. Screening upper gastrointestinal endoscopic evaluation revealed a large intraluminal polypoid lesion occluding the distal portion of the esophagus. Surgery was performed with resection of the distal esophagus and proximal stomach. The histopathologic examination of this lesion revealed an exuberant polypoid gastric epithelium with areas of low-grade dysplasia, high-grade dysplasia, and focal intramucosal carcinoma. A few residual foci of specialized intestinal metaplasia consistent with Barrett's esophagus without dysplasia were identified at the proximal and distal ends of the lesion. Immunohistochemically, this lesion revealed a pattern of expression of apomucins (MUC5AC diffusely positive, MUC1 and MUC6 focally positive, and MUC2 negative) consistent with a gastric foveolar phenotype. In addition, in the dysplastic areas, there was high Ki-67 labeling index and no overexpression of p53 protein. In our opinion, this case represents a precursor lesion of an extremely well-differentiated adenocarcinoma of gastric foveolar phenotype that has been previously documented in the stomach and in the duodenum and that now for the first time we report in the esophagus in association with Barrett's intestinal metaplasia.     

Histologic appearances of endoscopic gastric mucosal biopsies 10--20 years after partial gastrectomy.

Fifty-six symptomatic patients, who had had a partial gastrectomy 10--24 years previously for benign disease, were examined by endoscopy and multiple mucosal biopsies. No patient had a completely normal gastric mucosa. Varying degrees of gastritis, intestinal metaplasia, foveolar hyperplasia and dysplasia were seen. Seventeen patients (30%) had extensive areas of dysplasia associated with acute or chronic inflammation. Severe dysplasis, however, was detected in only one case. In five patients a "diffuse type" carcinoma of the gastric stump was found. While it is generally accepted that significant dysplasia (moderate or severe dysplasis) is premalignant, the degree of risk is unknown. This makes management of individual patients difficult.     

Gastric pit dysplasia in adjacent gastric mucosa in 414 gastric cancers: prevalence and characteristics

Despite wide acceptance of the chronic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence, especially for intestinal-type gastric adenocarcinoma, the precise nature of the subtle precursor lesions of gastric cancer remains to be delineated. For example, pit dysplasia with surface foveolar maturation is not well defined, nor is its prevalence and biological characteristics well characterized. We have evaluated the surrounding gastric mucosa of 414 gastric cancers for the presence of gastric pit dysplasia. We investigated its relationship with various clinicopathological and immunophenotypic features of gastric adenocarcinoma, as well as the severity and extent of any surrounding gastritis and intestinal metaplasia. p53 expression and Ki-67 proliferation index were also evaluated. We have found that 21.0% (n=87) of gastric cancer cases showed pit dysplasia in adjacent gastric mucosa. Gastric cancers with pit dysplasia were significantly associated with older age, male sex, body/fundic location, and intestinal histologic type (P<0.05). Interestingly, gastric mucin-containing intestinal metaplasia (incomplete intestinal metaplasia) was highly associated with adenocarcinoma with pit dysplasia (P=0.000). In addition, MUC6 expression in gastric adenocarcinoma was associated with pit dysplasia (P=0.036). p53 overexpression and increased Ki-67 proliferation index were more evident in gastric pit dysplasia compared with adjacent gastric mucosa. We suggest that gastric pit dysplasia is an important candidate precursor of gastric adenocarcinoma and may represent another morphologic step in the pathogenesis of gastric adenocarcinoma, especially of intestinal type. More detailed prospective studies are needed to determine the precise significance of these findings.     

Gastric Pouch Adenocarcinoma and Tubular Adenoma of the Pylorus: A Field Effect of Dysplasia following Bariatric Surgery

There are reports of gastric carcinoma following bariatric surgery, but it is unclear if these procedures predispose to malignancy.We present a case of a 60-year-old man who, 15 years after vertical banded gastroplasty (VBG), had a massive upper GI bleed. Endoscopy revealed a large tumor of the gastric pouch. Histology confirmed an intestinal type of gastric adenocarcinoma arising in a background of H. pylori-negative gastritis with atrophy, foveolar hyperplasia and intestinal metaplasia. An incidental tubular adenoma at the pylorus was also identified. The pathogenesis of gastric pouch carcinoma is discussed. The present example of neoplastic change in both the pouch and pylorus may indicate that a field effect for dysplasia develops subsequent to VBG.     

Histogenesis of gallbladder cancer with special reference to metaplastic changes and distribution of various mucins and CEA

In order to study the histogenesis of gallbladder cancer, metaplastic changes and dysplasia in the mucosal epithelium were investigated in 30 cases of gallbladder cancer and 300 cases of chronic cholecystitis. Intestinal metaplasia was observed more frequently in the cases of cancer, both in cancerous and non-cancerous tissues, than those of chronic cholecystitis. In addition, CPS III type of mucin, which is preferably demonstrated in the pyloric glands, was observed in the tumor cells of 50% of cancers. Thus, gastric metaplasia as well as intestinal metaplasia seems to be important as a predisposing lesion to gallbladder cancer. By means of reconstruction method carried out on the specimens of cancer, multifocal gradual transition among metaplasia, dysplasia and cancer was observed and dysplasia is an important step in cancer development. As for mucin secretion, the rate of sialomucin-containing cells was notably high in the lesions of dysplasia and cancer, increasing in intensity in this order, accompanied with positive CEA. The results of the present study support the hypothesis that cancer arises from such pre-existing mucosal lesions as metaplasia and dysplasia.     

The morphologic changes induced by hormone and radiation therapy on prostate carcinoma

The morphologic changes induced by hormone and radiation therapy were evaluated in prostate biopsy and prostatectomy specimens from patients with residual prostate carcinoma. The two therapeutic methods induce changes both in the nonmalignant and malignant residual prostatic tissue. Following hormone therapy, the nonmalignant prostatic tissue showed atrophy of prostatic acini associated with fibrosis, basal cell hyperplasia, degenerative changes of the secretory epithelial cells, and a marked decrease of high-grade intraepithelial neoplasia (HGPIN). In the fragments of residual carcinoma, squamous cell metaplasia, necrosis, and necrobiosis in the foci, vacuolization of the cell cytoplasm, smaller, rare nucleoli, intraluminal crystalloids, higher Gleason score associated with a lower capsular penetration, areas of necrosis and mitoses were found. Following radiation therapy, the nontumoral prostatic tissue showed an increased number of atrophic acini, squamous cell metaplasia, and presence of atypical glands. The morphologic changes induced by radiation therapy in the residual prostatic carcinoma were characterized by an abnormal architectural structure of the glands and presence of cell atypias correlated with the biochemical lowering of serum PSA.     

Epithelial proliferations in prostatic stromal tumors of uncertain malignant potential (STUMP)

Stromal tumors of uncertain malignant potential (STUMPs) are rare tumors characterized by an atypical, unique stromal proliferation of the prostate. Various stromal proliferations of STUMPs have been described; however, epithelial proliferations occurring within the STUMP have not been systematically described to date. We reviewed 89 cases of STUMP from our consultation service from 1990 to 2010. Nineteen cases without a glandular component were excluded. We next evaluated the glandular component of the remaining 70 cases of STUMP for glandular crowding and complexity, prostatic intraepithelial neoplasia (PIN), squamous metaplasia, urothelial metaplasia, basal cell hyperplasia, adenosis, and clear cell cribriform hyperplasia. In 58 cases (83%), the glandular component differed from glands on the same biopsy specimen uninvolved by STUMP. The most common abnormalities were glandular crowding in 35 of 70 (50%) and a very prominent basal cell layer in some glands in 32 of 70 (46%) cases. The next most frequent glandular variation from normal was prominent papillary infolding in 13 of 70 (19%) cases. Less-frequent epithelial changes within the STUMP were as follows: 10 of 70 (14%) showed cystically dilated glands; 7 of 10 (10%) had basal cell hyperplasia; 6 of 70 (9%) had urothelial metaplasia; 6 of 70 (9%) showed squamous metaplasia; 3 of 70 (4%) had cribriform hyperplasia; 3 of 70 (4%) had adenosis; and 1 case each showed high-grade PIN, low-grade PIN, and partial atrophy. The glandular component of STUMP was histologically normal in 12 (17%) cases. There was a tendency toward urothelial and squamous metaplasia in STUMPs with a phyllodes pattern, and a prominent basal cell layer in STUMPs with degenerative and cellular stroma. This is the first study to systematically describe the epithelial proliferations occurring in STUMP. This study suggests that, within STUMPs, there is epithelial-mesenchymal crosstalk, as has been described in benign prostate and in prostatic carcinogenesis. In unusual cases of STUMP, the epithelial proliferation may predominate to the extent that it can mask the diagnosis of STUMP.     

Simple and complex hyperplastic papillary proliferations of the endometrium: a clinicopathologic study of nine cases of apparently localized papillary lesions with fibrovascular stromal cores and epithelial metaplasia.

The clinicopathologic features of nine cases of papillary proliferation of the endometrium devoid of malignant nuclear features were studied. The patients ranged in age from 33 to 71 years (median 57 years). All were postmenopausal, except the youngest. The most common symptom was postmenopausal bleeding. Two patients were receiving hormonal replacement therapy and two were taking megestrol acetate. Two lesions were incidental findings in a hysterectomy specimen. Seven were diagnosed in endometrial biopsy or curettage specimens. In six cases (67%) the lesion involved an endometrial polyp. In all cases the papillae had fibrovascular stromal cores and variable degrees of branching. Two architectural patterns were found. A simple papillary pattern with involvement of only a few glands and little epithelial proliferation occurred in five cases, including three that were entirely intracystic. A complex papillary pattern with more extensive involvement of endometrial glands, a greater degree of branching of the papillae, and cellular tufting occurred in four cases. One or more metaplastic epithelial changes occurred in all cases, including endocervical-type mucinous metaplasia in nine cases (90%), eosinophilic cell change in eight (89%), ciliated cell change in seven (70%), focal squamous metaplasia in two cases (22%), and hobnail cell change in two (22%). Mitotic figures were found in three cases. In four lesions (44%), all with a complex papillary pattern, the proliferating cells had mild nuclear atypia. Three of these patients underwent hysterectomy within 5 months. Simple nonpapillary hyperplasia and two endometrial polyps were found in one patient, complex nonpapillary hyperplasia in one, and atrophic endometrium in the other. Two patients had additional endometrial samplings within 4 months that contained small residual simple papillary lesions. One of these had another biopsy at 16 months that showed only atrophy. One patient had no subsequent diagnostic or therapeutic procedures. One patient was a recent case. Of the three patients with intact uteri and appreciable follow-up, all were alive and well at 14, 96, and 102 months, respectively. We conclude that these papillary proliferations are a form of hyperplasia that is closely associated with endometrial epithelial metaplasia. Polypectomy and/or curettage may be effective in removing them because they often are localized lesions. Although all of our patients had an uneventful outcome, the number of cases is small. Our findings question the validity of diagnosing endometrial lesions as well-differentiated carcinoma solely because of a complex papillary architectural pattern.     

Use of keratin 903 as an adjunct in the diagnosis of prostate carcinoma

The identification of basal cells is often helpful in excluding a diagnosis of prostate carcinoma. However, it can be difficult to distinguish basal cells from underlying fibroblasts or an artifactual two-cell layer in neoplastic glands. To determine the usefulness of anti-keratin antibody 903 for identifying basal cells in glandular patterns sometimes confused with carcinoma, we examined frozen sections from radical prostatectomy specimens and formalin-fixed needle biopsy, radical prostatectomy, and transurethral resection specimens. Atrophic glands, basal cell hyperplasia, intraductal severe dysplasia and various grades of carcinoma were examined. Also evaluated were cases of atypical adenosis, defined as clusters of small glands that mimic low-grade carcinoma yet focally appear to have a basal cell layer and merge with more recognizable benign glands. Almost all normal glands showed some staining, although it was often discontinuous with formalin fixation. Intraductal dysplasia stained in a manner similar to normal glands. Ninety-two percent of atrophic glands and 88% of glands in basal cell hyperplasia stained. Sixty-one percent of the glands in atypical adenosis stained intensely but discontinuously. All grades of adenocarcinoma lacked any immunoreactivity. These results indicate that keratin 903 is useful in the diagnosis of prostatic carcinoma because positive staining identifies a questionable focus as benign whereas negative staining helps to substantiate the diagnosis of carcinoma.     

The expression of the blood related antigens in intestinal metaplasia of the stomach in gastric cancer

The monoclonal antibodies detecting blood group related antigens of the Lewis systems have been used to define the immunoanatomic distribution of these antigens within the normal gastric mucosa and in gastric cancer tissues. In this study we analysed the presence of these antigens in histologically intestinal metaplasia of the stomach by the immunoperoxidase method. In normal gastric mucosa, Lewisb was distinctly expressed in normal foveolar epithelia and Lewisa was present in foveolar epithelia in half of the cases. Lewisx and Lewisy were detected in deep gastric glands. In intestinal metaplasia, more pronounced expression of Lewisa and decreased expression of Lewisb were observed. Lewisx and Lewisy were absent in most specimens of intestinal metaplasia. These pattern of expression of Lewis antigens in intestinal metaplasia were very similar to those observed in well and moderately differentiated adenocarcinomas of the stomach. These results indicate that well and moderately differentiated adenocarcinomas of the stomach have very similar character with the intestinal metaplasia in terms of the Lewis blood group antigen expression.     

Differential expression of galectin-3 in papillary projections of malignant and non-malignant hyperplastic thyroid lesions

Galectin-3 is a a beta-galactoside binding protein recently proposed to be a promising presurgical molecular marker for distinguishing benign from malignant thyroid neoplasms. We analyzed galectin-3 expression immunohistochemically in papillary areas of hyperplastic lesions of benign thyroid tissue in comparison with malignant papillary projections of papillary thyroid carcinoma (PTC). A monoclonal antibody to galectin-3 and ABC immunohistochemical technique were used to evaluate galectin-3 expression in 26 cases of benign papillary hyperplasia (8 cases of hyperplastic adenoma, 8 cases of hyperplastic colloid goiter, 10 cases of Graves disease) in comparison with 25 cases of PTC. Immunohistochemical results showed no reactivity for galectin-3 in papillary areas of benign hyperplastic lesions. Strong cytoplasmic galectin-3 immunoreactivity was found in all 25 cases of PTC. These results show that galectin-3 expression is a feature of malignant papillary projections but not of benign papillary hyperplasia. Thus, the immunohistochemical evaluation of galectin-3 might contribute to differential diagnosis between malignant and benign thyroid lesions with papillary projections.     

Adenomatous and foveolar gastric dysplasia: distinct patterns of mucin expression and background intestinal metaplasia

Gastric epithelial dysplasia (GED) can be morphologically categorized into adenomatous (or intestinal) and foveolar (or gastric) types. Although limited genetic differences have been demonstrated between these subtypes, the expression of various mucins has not been systematically evaluated in this context. Endoscopic mucosal resections from 69 cases of GEDs were evaluated for the expression of MUC2, MUC5AC, MUC6, and CD10. The results were correlated with morphologic categorization and clinicopathologic parameters. GED was classified as adenomatous, foveolar, or hybrid (showing features of both types), on the basis of histologic evaluation. The neighboring intestinal metaplasia (IM) was also evaluated. An adenomatous morphology was seen in 45%, hybrid type in 33.3%, and a "pure" foveolar type was seen in 21.7% of the cases. Foveolar GED was often depressed/flat on endoscopy and showed a statistically significant association with high-grade morphology (P = 0.046). Immunohistochemistry confirmed the histologic stratification. The foveolar and hybrid types were more often positive for MUC5AC (P = 0.0001 for both) and negative for CD10 (P = 0.019 and 0.016, respectively) as compared with adenomatous GED. High-grade morphology was associated with MUC5AC expression regardless of the morphologic phenotype (P = 0.026). Foveolar (73.3%) and hybrid (86.9%) GEDs were associated more often with IM showing a retained expression of gastric type mucin than adenomatous GED (29%) (P < 0.01 for both). In contrast, adenomatous type (58.1%) of GED was significantly associated with IM showing a complete intestinal phenotype (CD10+) compared with the foveolar (13.3%) and hybrid types (17.4%) of GED (P = 0.005 for both comparisons). In conclusion, our study indicates that foveolar and adenomatous types of GED have distinct clinicopathologic features, mucin profiles, and association with different types of IM.     

转录因子FOXO4与胃癌及Hp感染关系的临床研究

目的:探讨FOXO4在胃癌发生过程中的表达、临床意义及其与幽门螺杆菌(Hp)感染的关系。方法:应用免疫组织化学SP法分别检测16例正常胃黏膜、26例慢性萎缩性胃炎伴肠上皮化生、36例异型增生胃黏膜及60例胃腺癌组织中FOXO4的表达,并检测患者Hp感染状况。结果:FOXO4在正常胃黏膜、慢性萎缩性胃炎伴肠上皮化生、异型增生胃黏膜及胃腺癌组织中的阳性率分别为100%、84.6%、69.4%和40.0%,胃腺癌组阳性率显著低于正常对照组(P<0.01)。FOXO4的阳性率在高、中分化和低分化型胃腺癌组织中呈现递减趋势,且其表达和淋巴结转移密切相关(P<0.05)。慢性萎缩性胃炎伴肠上皮化生及胃腺癌组织中FOXO4表达与Hp感染之间均无明显相关性(P均>0.05)。癌前病变组织中FOXO4表达与Hp感染率之间呈明显正相关(P<0.01)。结论:在胃黏膜癌变过程中,FOXO4的表达和作用逐渐下调;在癌前病变组织中FOXO4表达和Hp感染密切相关。     

在分子生物学水平上对膀胱癌的发生与治疗进行深入的研究

在分子生物学水平上对膀胱癌的发生与治疗进行深入的研究马腾骧Ａｍｏｌｅｃｕｌａｒｐａｔｈｏｌｏｇｉｃａｌｓｔｕｄｙｏｆｔｈｅｃａｒｃｉｎｏｇｅｎｅｓｉｓｏｆｔｒａｎｓｉｔｉｏｎａｌｅｐｉｔｈｅｌｉｕｍｂｌａｄｄｅｒｃａｎｃｅｒ￥ＣｈａｎｇＪｉ－ｗｕ；Ｍ...     

Pyloric gland adenoma: an entity distinct from gastric foveolar type adenoma

Pyloric gland adenoma (PGA) is a rare neoplasm demonstrating gastric epithelial differentiation. In this series, we studied 41 PGAs from 36 patients. We compared them to 28 gastric foveolar type gastric adenomas (GTAs) from 25 patients. PGAs occurred in an older population with a mean age of 73 compared with 48 in GTAs (P<0.001). There was a significant female predominance, particularly for gastric PGAs. Morphologically, PGAs were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing round nuclei and pale to eosinophilic cytoplasm with a ground glass appearance. The cells lacked an apical mucin cap, a feature distinct from GTAs. An immunohistochemical panel of mucin core peptides (MUCs) and CDX2 was performed on a subset of the lesions. All PGAs expressed MUC6 with coexpression of MUC5AC, whereas GTAs expressed predominantly MUC5AC without MUC6. Both lesions lacked CDX2 and MUC2 except in areas of intestinal metaplasia (IM) found in some PGAs. Histologic features consistent with conventional dysplasia were found in 26 (63.4%) PGAs. Using a 2-tier grading system, 5 (12.2%) cases demonstrated low-grade dysplasia whereas 21 (51.2%) cases showed high-grade dysplasia including 5 (12.2%) cases with an associated intramucosal or more deeply invasive adenocarcinoma. This was significantly different from GTAs; all cases showed only low-grade dysplasia (P<0.001). In addition, 60% of gastric PGAs were associated with IM in the surrounding mucosa and 40% of lesions arose in a background of autoimmune gastritis, whereas these 2 conditions were only associated with 1 case (3%) of GTA. In summary, PGA is a distinct entity. Despite its bland histologic appearance, it is much more likely to be accompanied by background IM and autoimmune gastritis and can evolve into invasive adenocarcinoma displaying pyloric gland differentiation.