胃癌组织HLA－I类和DR分子免疫组化研究

本文应用免疫组化法对６４例胃癌、癌旁组织和６例胃溃疡大致正常胃粘膜冰冻和石蜡切片进行了染色．结果表明，正常胃粘膜和癌旁胃粘膜上皮细胞ＨＬＡ－Ｉ类分子表达阳性，其着色较均一，ＨＬＡ－ＤＲ染色均阴性．胃癌细胞Ｉ类分子表达缺失（２７／６４例），与癌旁上皮比较差异显著（Ｐ＜０．０１）。粘液细胞癌和低分化癌Ｉ类分子缺失率显著高于高分化癌（Ｐ＜０．０２５）．此外，发生肿瘤转移的病例Ｉ类分子缺失率（１２／１５例）显著高于无转移组（１／５例，Ｐ＜０．０２５）．ＤＲ分子在癌组织表达阳性，其阳性率高达５３．１％（３４／６４例）．低分化癌ＤＲ分子阳性率亦显著高于高分化癌和中分化癌，未分化癌ＤＲ分子阳性率亦显著高于高分化癌（Ｐ＜０．０１～０．０５）．提示（１）ＨＬＡ－Ｉ类分子表达缺失可能与癌细胞逃避宿主免疫监视发生润浸生长和转移有关；（２）分化程度不同的癌组织ＨＬＡ－Ｉ类分子表达差异显著，提示癌细胞分化可能影响Ｉ、Ⅱ类分子表达和肿癌抗原呈递；（３）ＨＬＡ－Ｉ类和ＤＲ分子表达异常可能是上皮恶性转变的标志之一．     

Immunohistologic study of the localization of organ-specific antigens of the stomach and intestine and carcinoembryonic antigen in normal and pathologically altered stomach tissues

Localization of organospecific gastric and intestinal antigens, as well as of carcinoembryonic antigen (CEA) was studied by an indirect immune peroxidase method on the sections of fetal stomach, normal definitive stomach, gastric mucosa with features of superficial and deep gastritis, enterolysis and dysplasia, as well as in gastric tumours. Normally, pepsinogen was found to localize in zymogen cells and to disappear in enterolysis and dysplasia of gastric mucosa. Intestinal antigen is absent from the normal mucosa, but is found in all the cases with enterolysis and dysplasia. CEA is most specific for dysplasia of gastric epithelium. In cancers of intestinal type pepsinogen was found in 54%, intestinal (colonic) antigen in 37.5%, CEA in 62.5%. In diffuse type cancers pepsinogen was absent, intestinal antigen was found in 76.9%, CEA in 92% of tumours.     

Cancerous and non-neoplastic stem cells in the stomach similarly express CD44 and CD133

CD44 and CD133 have been considered as cancer stem cell (CSC) markers. Stem cell markers are rarely described in healthy stomach tissues. However, the clinicopathological and prognostic value of CD44 and CD133 in gastric cancer remains controversial. This study investigated the expression of CD44 and CD133 in gastric cancer and non-neoplastic gastric mucosa. We used samples of primary gastric adenocarcinomas (n = 69), metastatic lymph nodes (n = 30), intestinal metaplasia (n = 17), and histologically normal gastric tissues of surgical margins (n = 54). The expression of CD44 and CD133 were studied in samples by immunohistochemistry. Fisher’s exact test and a logistic regression model were used in this study. CD44 expression was observed in 12% of samples with intestinal metaplasia, 20% with lymph node metastases, 22% with normal mucosa, to 30% of samples with primary tumors. Most of these positive tumors showed immunostaining in less than 4% of cancerous cells, mainly in the diffuse type. CD133 expression was observed in 7% (intestinal metaplasia) to 46% (normal mucosa). In the positive cases of cancer (24%), in most of them, less than 3% of cells were marked. CD44 and CD133 expression in the histologically normal gastric mucosa was restricted to the deeper regions of the gastric crypts at the level where stem cells and progenitor cells are usually found. CD44 and CD133 expression occurs in few gastric cancer cells, mainly in diffuse carcinomas, and are expressed in histologically normal gastric mucosae. None of the markers are specific for cancer and are also present in intestinal metaplasia and the normal mucosa.     

T (Thomsen–Friedenreich) antigen and other simple mucin-type carbohydrate antigens in precursor lesions of gastric carcinoma

In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple-mucin type carbohydrate antigens (Tn. sialyl-Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl-Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl-Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen.     

消化道恶性肿瘤的临床分析

目的 探讨消化道恶性肿瘤患者的发病情况,为制定、评估和调整防控策略提供参考依据。方法 检索某院2017年1月1日~2018年12月31日住院病案首页数据中ICD-10编码C15.0~C26.9的消化道恶性肿瘤住院患者,共3250人次,同时将该院体检中心3300名健康体检人群的血型资料作为对照。将消化道恶性肿瘤患者分为肝胆癌、肠道癌、胃癌、食管癌、胰腺癌5组,分析各组发病人数、性别、发病年龄、血型等分布特点。结果 该院消化道恶性肿瘤主要以肝胆癌为主,占全部消化道恶性肿瘤一半以上,为66.37%,其次是肠道癌（19.05%）;发病风险男性高于女性,高峰集中在51~70岁;不同血型患消化道肿瘤的比例不同,A型、O型人群患胃癌和食管癌的比例高。结论 该地区消化道恶性肿瘤以肝胆癌和肠道癌最常见,且恶性肿瘤的发生除了跟饮食习惯有关外,可能与血型也有一定的关系,针对高危人群人群应加强防控。     

Histologic types and possible initial stages in early gastric carcinoma.

Among 2003 gastric specimens from 301 patients, diagnosis for carcinoma was made in 45 cases. Examination of resection preparations revealed 36 cases of deep invasive stomach carcinoma and 9 cases of early gastric cancer confined to mucosa and/or submucosa. Carcinomatous proliferations limited to mucosa or submucosa are classified in three histologic types: intestinal (adeno), mucocellular (signet ring cell), and anaplastic (solid) type of early gastric cancer. Mixed types have been found combining the first and the second, or the second and the third type. One case presented a mixture of all three types. Possible precursor or initial stages of all three types were found in further 31 biopsies. Some of them were glandular lesions in superficial parts of the mucosa; this kind has been described previously as possible preneoplastic stage of the intestinal type of early gastric cancer. "Signet ring cell drippings" from lower parts of tubule necks were recorded as an initial form of the signet ring cell type. The process is interpreted as detaching of isolated signet ring cells from a gland neck zone in progressing atypical transformation. An early neoplastic stage of the anaplastic (solid) type of early gastric cancer is identified in the "gland neck dysplasia" located exclusively in the antrum between surface mucosa and antrum glands. This lesion appears rich in cells and stretched like a broad ribbon. Early gastric cancer of this third type will arise in the very same location. Conclusions from formal histogenesis suggest that the signet ring cell type and the anaplastic (solid) type of early gastric cancer might start in the lower part of tubule necks. In consequence, the neck region of gastric glands could be the critical field of malignant transformation in the gastric mucosa. Long-term follow-up studies will be needed to verify these observations and their interpretation.     

Epithelial metaplasia in gastric or intestinal type and malignant transformation in mucinous ovarian tumors]

By using HE, histochemistry and immunohistochemistry stainings, 64 cases of mucinous tumors of ovaries including 24 benign, 29 borderline and 11 malignant cases were studied. The epithelial lining was divided into 4 types, namely: cervical, intermediate, gastric and intestinal types. According to the morphological and histochemical characteristics the intermediate type epithelium might be a transitional form between the cervical type and the gastric or intestinal metaplastic type. Argyrophil cells appeared only in the gastric or intestinal type epithelium, and malignant transformation was also to be detected in these 2 types. The constituents and amounts of mucin showed obvious difference among these four types of epithelium. The amount of neutral mucin was prominently decreased during the process of malignant transformation of the intestinal type epithelium and the expression of sulphomucin was also slightly predominant than the sialo-mucin's, but these changes were not noticed during the malignant change of gastric type epithelium.     

An immunohistochemical study of the localization of embryonic prealbumin in the gastric mucosa in chronic gastritis and hyperplastic polyps

The location of embryonic prealbumin (EPA) was investigated by indirect immune peroxidase test in gastric mucosa: 16 cases of chronic gastritis without malignant tumour and in 48 cases of gastric carcinoma. EPA in the mucosa was found in 35% cases of carcinoma outside the tumour and 31.3% cases of mucosa without tumour. The highest expression of EPA was found in stromal component of hyperplastic polyp without malignancy. Comparison of EPA and carcinoembryonic antigen in tissue did not reveal the presence of correlation between these oncofetal markers. Most likely this antigen is of a reactive nature and it can not be used for the evaluation of the probability of gastric mucosa malignant transformation.     

Expression of blood group-related antigens, ABH, Lewis(a), Lewis(b), Lewis(x), Lewis(y), CA19-9, and CSLEX1 in early cancer, intestinal metaplasia, and uninvolved mucosa of the stomach.

The expression of blood group-related antigens, A, B, H type 2, Lewis type 1 (Lewis(a) [Le(a)] and Lewis(b) [Le(b)]), Lewis type 2 (Lewis(x) [Le(x)] and Lewis(y) [Le(y)]), sialylated Le(a) (CA19-9), and sialylated Le(x) (CSLEX1), was analyzed sequentially with immunohistochemical methods in early gastric cancer, intestinal metaplasia, and uninvolved gastric mucosa obtained from 35 surgical specimens of patients who underwent gastrectomy. The high incidence of the inappropriate expression of Lewis type 1 antigens and the deletion of H and Lewis type 2 antigens was observed similarly in patients with cancer and intestinal metaplasia. The acquisition of CA19-9 and CSLEX1 and the deletion of B antigen frequently were found in intestinal-type cancer and all types of intestinal metaplasia. The simultaneous deletion of A antigen was detected only in the combination of intestinal-type cancer and incomplete-type intestinal metaplasia. Thus the present study shows that similar changes of tissue antigenicities exist in early gastric cancer and intestinal metaplasia.     

胃癌单抗检测活检粘膜组织833例结果分析

应用胃癌单抗ID1-2对833例内窥镜活检组织进行了免疫学荧光检查,胃癌阳性检出率为81.6％:胃溃疡为32.7％;肠化生性蒌缩性胃炎为40.0％;食管和结肠腺癌分别为60.0％和62.5％,与单纯性萎缩性胃炎和浅表性胃炎的阳性检出率相比有非常显著的差异(P<0.01)。表明ID1-2单抗可用于检测活检粘膜组织中的癌细胞以及具有癌细胞相关抗原的癌前病变组织,如果与内窥镜及常规病理学检查联合应用,将可进一步提高早癌的阳性检出率。     

卵巢粘液性肿瘤组织发生的初步探讨

目的：初步探讨卵巢粘液性肿瘤（ＯＭＴ）的组织发生。方法：用组织化学染色方法观察９１例ＯＭＴ上皮的粘液分泌。按粘液性质将上皮分为３型：胃型、肠型和中间型。并将肿瘤分为简单型及混合型。结果：良性５６例中,４５例为混合型,其中２２例由３种上皮成份组成,２３例含２种上皮,另有１１例为简单型。中间型、胃型及肠型３种上皮在良性肿瘤中的出现频率分别是４０／５６、３５／５６、２９／５６。２１例交界性、１４例恶性Ｏ     

胃癌及其胃粘膜病变的粘液组织化学和免疫组织化学的研究

对114例不同组织类型的胃癌及其胃粘膜组织，进行了粘液组织化学和癌胚抗原免疫组织化学研究。结果表明：肠上皮化生（肠化）检出率在萎缩性胃炎对照组高于癌组，癌组的肠化检了率非癌组织高于癌旁组织。肠化细胞是成熟性增生，它和不典型增生及癌均未发现有过渡形式。不典型增生偶见细胞癌变，有时也不易和高分化腺癌鉴别。认为肠化是对有害因子刺激的适应性变化，而不典型增生多系癌前病变。癌胚抗原在不同类型的胃癌组织中分布和量的不同除标志着分泌和释放不同外，可能也有助于判断癌的预后。     

Association of Helicobacter pylori-dependent gastritis with gastric carcinomas in young Japanese patients: histopathological comparison of diffuse and intestinal type cancer cases

AIMS: The causal relationship of H. pylori gastric colonization with gastric cancer development has not as yet been fully elucidated. The prevalence of H. pylori infection increases with age in the asymptomatic population in Japan, and reaches a high plateau in those older than 40 years. The objective of this study was to assess the link between H. pylori and gastric carcinomas in patients younger than 40 years. METHODS AND RESULTS: Detection of H. pylori and assessment of background mucosa based on the Sydney system was performed histopathologically for 40 Japanese gastric cancer cases younger than 40 years and compared with 40 age- and sex-matched controls. H. pylori infection in gastric mucosa was detected significantly more frequently (P < 0.001) in patients with cancer (29/40; 72.5%) than in controls (11/40; 27.5%). Additionally, by histopathological comparison between intestinal (18 cases) and diffuse (70 cases) types of young gastric cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist with acute and chronic inflammation in the background mucosa of both intestinal and diffuse types, being significantly more prevalent than in young controls. CONCLUSIONS: As well as the high prevalence of H. pylori in young subjects with gastric cancer, it is clear that persistent infection induces mucosal damage, resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis could play an essential role in the early development of neoplasia in the stomach.     

Altered expression of Lewis antigen on tissue and erythrocytes in gastric cancer patients

To elucidate the clinical significance of phenotypic alterations of Lewis antigen in gastric cancer patients, we investigated Lewis antigens by analyzing the genotypes of the Le and Se genes and by comparing the results obtained with the phenotypic expression of Lewis antigen in gastric cancer tissue and blood cells. One hundred and twenty gastric cancer patients were examined and compared with respect to Lewis blood phenotype and genotype. The expression of Le(a), Le(b), sialylated Le(a), and sialylated Le(x) antigens was immunohistochemically examined in uninvolved gastric mucosa, intestinal metaplasia, and cancerous tissue. We also analyzed the significance of Lewis antigen expression by analyzing patient survival. The frequencies of the Lewis phenotypes of RBCs corresponding to Le(a+b-), Le(a-b+), and Le(a-b-) were 16%, 58%, and 26%, respectively. The Le and le allele gene frequencies calculated from genotyping in gastric cancer patients were 0.623 and 0.377, respectively. The frequency for Le(a-b-) of the RBC phenotype had a tendency to be higher in cancer patients than in normal healthy Koreans. However, no difference in the Lewis gene frequency was found between these gastric cancer patients and healthy persons. The phenotype of Le(a-b+) was most prevalent in uninvolved gastric mucosal tissue, whereas the most prevalent form in tumor tissue was Le(a-b-). Sialyl-Le(a) and sialyl-Le(x) antigens were hardly detectable in uninvolved gastric mucosa, whereas the two antigens were expressed highly in intestinal metaplastic mucosa and tumor cells. In conclusion, the loss of Lewis antigen expression in tissue and on RBCs in gastric cancer patients is not a result of genetic influences, but rather a result of sialylation in tissue. We also confirm that poor prognosis is associated with dimeric sialyl-Le(x) and vascular spread.     

Cytokeratin expression patterns of gastric carcinomas according to Lauren and Goseki classification.

The Goseki system is a new gastric carcinoma classification system that classifies gastric carcinomas as grade I (intestinal type), grade II (mucinous type), grade III (mucin-poor, diffuse infiltrating type), and grade IV (signet ring cell type). The main advantage of the Goseki classification may be to separate these distinct entities into different groups. CK7 is not observed in normal gastric mucosa but can be detected in chronically inflamed gastric mucosa and coexists with incomplete intestinal metaplasia. CK20 can be observed in the superficial foveolar epithelium and mature goblet cells. The aim of this study was to examine the cytokeratin expression profiles in gastric carcinomas that are classified according to both the Goseki and Lauren systems. CK7, CK8, CK19, and CK20 were applied to the paraffin sections of 66 gastric carcinoma cases. The cytokeratin expression patterns were grouped as CK20+/CK7+, CK20+/CK7-, CK20-/CK7+, or CK20-/CK7-. The results were examined statistically. CK20 immunoreactivity was observed in 18%, 24%, and 31% of grade I, III, and IV cases, respectively. The CK20+/CK7- pattern was observed in 20% of the grade IV and 66.7% of the grade II carcinomas and was not observed in grade I or grade III tumors (P<0.0001). Goseki grade III and IV carcinomas originate from superficial gastric mucosa, but grade III carcinomas are poorly differentiated. Goseki grade II carcinomas have a specific immunophenotype other than intestinal-type gastric tumors. The Goseki classification seems to be superior in identifying poorly and well-differentiated forms of diffuse infiltrating carcinomas and mucinous carcinomas.     

卵巢粘液性囊腺瘤恶变和肠上皮化生的关系

Ninety cases of ovarian mucinous tumors were studied histologically and histochemically. Intestinal metaplasia was found in 48.2% (14/29) of benign. 73.6% (14/19) of borderline and 92.9% (39/42) of malignant mucinous cystadenomas. The differences between these three groups are statistically significant (P less than 0.01). Among 67 cases of intestinal metaplastic mucinous tumors, 43 contained argyrophil cells, and 36 contained argentaffin cells. The coexistence of intestinal metaplasic and uterocervical canal type epithelia was observed in 2/3 of borderline and 1/3 of malignant intestinal mucinous cystadenomas. In addition, there were 5 cases of borderline and 3 cases of malignant uterocervical canal type mucinous cystadenomas among the 90 cases. It is evident that the malignant transformation of ovarian mucinous cystadenoma was closely related to intestinal metaplasia. Anyhow, it seems not necessary for malignant transformation of all ovarian mucinous cystadenomas to pass through a stage of intestinal metaplasia: some of the malignant mucinous cystadenomas were considered probably originating from the uterocervical canal type epithelium.     

单克隆抗体MG7在胃癌癌前病变组织中的免疫组织化学研究

作者应用胃癌单克隆抗体MG7对289例胃粘膜活检标本进行PAP免疫组织化学观察,发现伴有肠化生的萎缩性胃炎组(20.0％)与伴有肠化生的癌旁粘膜组(62.1％)间、弥漫型胃癌癌旁粘膜肠化生组(41.7％)与肠型胃癌癌旁粘膜肠化生组(76.5％)间、轻型不典型增生组(23.9％)与中重度不典型增生组(54.0％)间,MG7-Ag表达阳性率均有显著性差异(均为P<0.01)。在胃癌组织中MG7-Ag表达阳性率为87.8％,而8例正常胃粘膜均阴性。结果表明,胃癌单克隆抗体MG7对胃癌的诊断具有较高的特异性;肠化生与胃癌(尤其是肠型胃癌)的发生有密切关系;对MG7-Ag表达阳性的肠化生和异型增生患者加强随访,将有利于胃癌的早期发现。     

Gastric and Intestinal Phenotypic Expression of Human Stomach Cancers as Revealed by Pepsinogen lmmunohistochemistry and Mucin Histochemistry

Gastric and intestinal phenotypic expression in 223 surgically obtained primary gastric cancers and their histogenetic relationship to intestinal metaplasia in the surrounding gastric mucosa were studied by mucin histochemistry and pepsinogen (Pg) immunohistochemistry. Histochemical differentiation of mucins (paradoxical concanavalin A, the galactose oxidase-Schiff sequence and sialidase galactose oxidase Schiff) and immunohisto chemical staining of Pgs I and II, allowed differentiation of gastric cancer cells from different histological categories into gastric elements including mucous neck cells, pyloric gland cells and surface mucous cells or intestinal elements including goblet cell and intestinal absorptive cell types. Of 122 papillary and tubular adenocarcinomas, 33 (27.1%) consisted mainly of gastric type cells and 42 (34.4%) predominantly of intestinal type cells. The remainder (38.5%) consisted of mixtures of gastric- and intestinal-type cells. Of 101 poorly differentiated adenocarcinomas, signet ring cell carcinomas and mucinous adenocarcinomas, 59 (58.4%) consisted mainly of gastric-type cells and 20 (19.8%) mainly of intestinal-type cells. Seven out of 35 papillary and tubular adenocarcinomas consisting mainly of gastric type cancer cells were surrounded by mucosa with intestinal metaplasia. Conversely, 10 out of 40 papillary and tubular adenocarcinomas consisting mainly of intestinal-type cancer cells were observed in non metaplastic gastric mucosa. Thus no relationship as regards intestinal phenotypic expression was found between gastric cancers and surrounding gastric mucosa.     

Early gastric cancer. Clinico-pathological analysis of 125 cases of early gastric cancer (EGC)

The frequency and the pathological findings of 125 early gastric cancers (ECGs), and particularly of small and minute lesions, were evaluated in a retrospective study of 839 surgical specimens of gastric carcinoma. Sixty two ECGs were believed to have risen from gastric epithelium, 27 from areas of intestinal metaplasia, and 3 from cardio-pyloric mucosa. The remaining lesions showed mixed histological patterns. The most frequent macroscopic type was IIc (24.8%) followed by IIb (16.8%), I (16.8%), and III (14.4%). In 63 cases (50.4%) the cancer was limited to the mucosa. In all specimens, and particularly in small and minute lesions, the surrounding mucosa was accurately analyzed to detect any lesions, from which the cancer could have developed. Intestinal ECGs, especially if protruded, seem to arise from areas of intestinal metaplasia or of chronic atrophic gastritis. Rarely ECGs seem to stem from polypoid lesions both hyperplastic and adenomatous. On the contrary, most important seems to be the role of ulcerative lesions, since in 14 cases of our series, carcinomatous foci were observed within the regenerative epithelium covering the crater. No correlation was found between histologic type, size, staging, and frequency of node metastasis; this suggests the existence of ECGs with different biologic behaviour.     

Clinico-pathological Analysis of 125 Cases of Early Gastric Cancer (EGC)

The frequency and the pathological findings of 125 early gastric cancers (ECGs), and particularly of small and minute lesions, were evaluated in a retrospective study of 839 surgical specimens of gastric carcinoma. Sixty two ECGs were believed to have risen from gastric epithelium, 27 from areas of intestinal metaplasia, and 3 from cardio-pyloric mucosa. The remaining lesions showed mixed histological patterns. The most frequent macroscopic type was IIc (24.8%) followed by IIb (16.8%), I (16.8%), and III (14.4%). In 63 cases (50.4%) the cancer was limited to the mucosa. In all specimens, and particularly in small and minute lesions, the surrounding mucosa was accurately analyzed to detect any lesion from which the cancer could have developed. Intestinal ECGs, especially if protruded, seem to arise from areas of intestinal metaplasia or of chronic atrophic gastritis. Rarely ECGs seem to stem from polypoid lesions both hyperplastic and adenomatous. On the contrary, most important seems to be the role of ulcerative lesions, since in 14 cases of our series, carcinomatous foci were observed within the regenerative epithelium covering the crater. No correlation was found between histologic type, size, staging, and frequency of node metastasis; this suggests the existence of ECGs with different biologic behaviour.