Distribution of basement membrane antigens in clinical gastric adenocarcinomas: an immunohistochemical study.

The distribution of laminin and collagen type IV in the basement membranes of 85 gastric adenocarcinomas was studied using immunoperoxidase techniques to check for invasive carcinoma. Lymph nodes with metastases were also studied in 23 cases. Thick and discontinuous staining of the basement membranes was observed in 12 cases of well differentiated adenocarcinoma; thin and discontinuous staining in 26 (12 well and 14 moderately differentiated adenocarcinomas); fragmentary staining in 36 (15 moderately and 21 poorly differentiated adenocarcinomas); and unrecognisable basement membrane staining in the remaining 11 cases of poorly differentiated adenocarcinoma. These patterns were largely related to the histological grade, the nuclear atypism and loss of polarity of tumour cells, and the degree of inflammatory infiltration.     

Remodeling of basement membrane in association with cancer invasion

Type IV collagen the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. In normal breast tissue, benign breast tumors, and in the intraductal components of invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were stained in all BM, whereas alpha 5 (IV) and alpha 6 (IV) chains were restrictively localized in a linear pattern in the epithelial BM. However, in invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were discontinuously or negatively stained in the cancer cell nest, and the assembly of alpha 5 (IV) and alpha 6 (IV) chains into the BM was completely inhibited. The results indicate that the mammary gland forms a second network of BM composed of alpha 5 (IV)/alpha 6 (IV) chains, in addition to the classic network of alpha 1 (IV)/alpha 2 (IV) chains. Remodeling of type IV collagen alpha chains during the development of invasive breast cancer seems to be differentially regulated, and to be associated with modification of histopathological findings.     

低氧时肺癌细胞侵润和迁移特性的变化及分子基础

目的:探讨低氧对肺癌细胞侵润、迁移特性的影响及其机制。方法:将肺癌细胞株置常氧(空气、5%CO₂)、低氧(5%O₂、5%CO₂、90%N₂)、无氧(95%N₂、5%CO₂)的不同氧环境中培养48 h后,用划痕法测定各组细胞的迁移能力,用羊膜内皮细胞模型测定各组细胞的侵润能力。同时将处理的细胞接种于裸鼠背部皮下,观察其生长情况及转移特点。同时分析上皮钙粘附素、β1-整合素的表达量。结果:低氧组细胞迁移能力、侵润能力显著高于常氧组。无氧组成瘤率和肺转移率显著低于常氧组和低氧组。低氧组上皮钙粘附素表达显著低于常氧组而β1-整合素表达量显著高于常氧组,无氧组两者均显著低于常氧组。结论:适度低氧可以下调肺癌细胞上皮钙粘附素表达,增加β1-整合素表达,增强癌细胞迁移力和侵润力。但是严重低氧使癌细胞粘附分子表达下降,生长增殖能力、迁移力和侵润力下降。     

Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis

The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (>80% positive cells) was significantly associated with the grade of tumour differentiation (p<0.01), with lymph node metastasis (p<0.01) and with BM degradation (p<0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p<0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma.     

Assessment of invasion in breast lesions using antibodies to basement membrane components and myoepithelial cells.

This paper describes immunostaining of consecutive sections from 15 cases of fibrocystic change of the breast (including 2 examples of intraductal papilloma), 4 ductal carcinomas-in-situ and 17 invasive carcinomas (4 tubular, 1 papillary, 2 lobular and 10 infiltrating ductal, NOS) with antisera to components of the basement membrane (BM), type IV collagen and laminin, and with the muscle antibodies actin and muscle-specific actin. A simple digestion technique was developed to improve the clarity of BM staining with these antibodies. The BM stains facilitated identification of small invasive foci through breaks in the BM in 2 of the cases which had been reported as pure intraductal carcinoma. Tubular carcinomas were surrounded by abnormal, fragmented, and focally discontinuous BM, a feature which could be used to distinguish this well-differentiated breast carcinoma sub-type from sclerosing adenosis, in which individual acini were invariably surrounded by a continuous BM. BM staining emphasized the fibrovascular core of intraductal papillomas, whereas the BM layer was absent in intraductal, cytologically malignant, papillary projections. Similarly, myoepithelial cells, stained with antisera to muscle actins, were identified in a continuous layer surrounding benign epithelial proliferations. These immunohistochemical staining techniques may thus assist the diagnostic histopathologist in differentiating between benign epithelial proliferations of the breast and well-differentiated invasive breast carcinoma, and in identifying foci of microinvasive carcinoma.     

Glomerular basement membrane anionic charge site changes early in aminonucleoside nephrosis.

Alterations of glomerular basement membrane (GBM) anionic (charge sites, CSs) in the development of proteinuria in a model of idiopathic nephrotic syndrome in man (puromycin aminonucleoside nephrotic syndrome [PAN] in the rat) were assessed quantitatively and sequentially early after disease induction. GBM CSs (known to consist mainly of heparan sulfate-rich proteoglycans) were stained in vivo and, in a separate group of animals by an in vitro method, with the cationic marker polyethyleneimine (PEI) studied by electron microscopic examination. Four hours after administration of PAN, there was a significant decrease in GBM lamina rara externa CSs: 18 +/- 0.7 versus 22.0 +/- 2.2 per 1000 nm GBM in controls by PEI injection and 17.2 +/- 2.7 versus 21.1 +/- 1.6 per 1000 nm GBM in controls by PEI in vitro staining. This CS alteration coincided with changes in glomerular epithelial cell morphologic characteristics (increased cytoplasmic organelles and rough endoplasmic reticulum) and preceded the detection of foot process broadening (at 24 hours) and increased urinary albuminuria (suggested at 12-24 hours, statistically significant at 36-48 hours). These results suggest that GBM CS-heparan sulfate proteoglycan alterations consisting of either decreased number and/or less anionic charge occur early in PAN and support a role for glomerular epithelial cell maintenance of GBM CS for normal glomerular function.     

Strain differences and the genetic basis of experimental autoimmune anti-glomerular basement membrane glomerulonephritis

Goodpasture's, or anti-glomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis, caused by autoimmunity to a component of the GBM, the non-collagenous domain of the α3 chain of type IV collagen [α3(IV)NC1]. To investigate the mechanisms of inflammation in glomerulonephritis and to test new approaches to treatment, animal models of glomerulonephritis, termed experimental autoimmune glomerulonephritis (EAG), have been developed in susceptible strains of rats and mice. This review article describes how these models of EAG have been developed over the past three decades, discusses the evidence for the involvement of both humoral and cell-mediated immunity in the induction and pathogenesis of glomerulonephritis in these models and highlights recent, emerging data that have identified potential candidate genes that may control the genetic susceptibility in these different strains of rats and mice. The identification of these susceptibility genes has lead to a better understanding of the genetic basis of this model of anti-GBM disease, which may be relevant to the immunopathogenesis of Goodpasture's disease, and more generally to the progression from autoimmunity to target-organ damage.     

脱细胞猪角膜表面基底膜成分的检测

背景：前期实验显示脱细胞猪角膜具有良好的组织相容性,可以支持角膜细胞和皮肤上皮细胞的生长。 目的：检测脱细胞猪角膜是否保存了利于角膜上皮细胞生长的重要组织结构—基底膜。 方法：利用荧光抗体对脱细胞猪角膜表面的基底膜成分(层粘蛋白和Ⅳ型胶原)进行免疫组织化学检测,荧光显微镜下观察脱细胞猪角膜表面是否保存了基底膜成分。 结果与结论：免疫荧光染色显示脱细胞猪角膜前基质表面层粘蛋白和Ⅳ型胶原呈阳性表达,与新鲜猪角膜表面基底膜的荧光表达相同,表明脱细胞猪角膜保存了利于角膜上皮细胞生长的基底膜。     

Distribution of basement membrane antigens in cryopreserved early embryonic hearts

The early embryonic heart is composed of two cylindrical epithelial layers, an inner endothelium and an outer myocardium. The cardiac jelly (CJ), an acellular accumulation of extracellular matrix (ECM), fills the space between the two epithelia. During development of the heart, a portion of the endothelial cells of the atrioventricular (AV) region differentiate into mesenchyme cells in a temporally and spacially specific manner. Although contiguous with those in the AV region, endothelial cells lining the ventricle never form mesenchyme in situ. At present, the mechanisms controlling the biphasic differentiation of the endothelium and the subsequent migration of cardiac mesenchymal cells are poorly understood. Although the CJ lies between two epithelial and is spatially equivalent to a basement membrane (BM), it has not traditionally been considered to be organized into a BM-like structure. The potential significance of this observation to developmental biology lies in the possibility that BM or their individual components (i.e., fibronectin (FN), laminin (LM), type IV collagen, and heparin sulfate proteoglycan (HSPG] may function as the regulatory site of epithelial differentiation and morphogenesis. A cryofixation technique was developed in order to determine the in situ immunohistochemical distribution of the BM components in the CJ. Results indicated that the CJ exists as the fusion between a larger myocardially derived BM having a lamina densa and an extended reticular lamina and an attenuated, endothelial-associated BM composed only of a lamina densa. Except for FN, the individual BM components were not all present during early stages, but instead appeared in a sequential manner, suggesting that all components of an adult-type BM are not required to initiate the assembly of a structural and functional BM during development. In the AV canal and outflow tract (OT), FN appeared as a progressively expanding gradient of material with the greatest density nearer the myocardium.     

Development of liver metastasis in colorectal carcinoma. With special reference to venous invasion and basement membrane laminin.

The development of hepatic metastases in 344 patients with colorectal carcinoma was examined for correlation with the presence of both venous invasion by the primary tumor and basement membranes in the tumor tissue. The former was detected by Victoria blue and hematoxylin-eosin staining and the latter by antilaminin antibody. A significant difference in the incidence of venous invasion was noted between patients with and those without liver metastasis at surgery. Basement membrane deposition was found in half of all cases of well differentiated adenocarcinoma, which was significantly high compared with other tumor types. This was more distinct in metastatic foci in the liver and lymph nodes than in the primary lesion, but less marked in intravascular tumor tissue. Basement membrane deposition was seen more frequently in Dukes' A tumors than in B tumors, although this was not statistically significant. No relationship was found between basement membrane laminin positivity and five-year survival, nor was there any correlation between the incidence of liver metastasis and tumor histologic type. Venous invasion was considered to be intimately related to the development of liver metastasis. Deposition of laminin-positive basement membrane was dependent on the grade of tumor differentiation, whereas it had no direct relation to the development of liver metastasis.     

Immunoreactivity of surfactant-apoprotein in adenocarcinomas, large cell and small cell carcinomas of the lung

Fifty seven adenocarcinomas, 43 large cell and 30 small cell lung carcinomas were immunohistochemically examined using monospecific IgG against pulmonary surfactant apoprotein. Six peripheral adenocarcinomas and one peripheral large cell carcinoma were found to be histogenetically related to type II pneumocytes. They showed an acinar, papillary or solid growth pattern. The immunohistochemical study using anti-surfactant apoprotein IgG gave a granular reaction product in both the cytoplasm and nucleus of tumor cells whose intensity was variable. Intranuclear inclusions were generally the most densely stained structures. These results suggest that lung carcinomas derived from alveolar type II cells are found not only in bronchioloalveolar tumors, but are also found in other types of adenocarcinoma and in large cell carcinomas.     

Differential basement membrane composition in multiple epithelioid haemangioendotheliomas of liver and lung

We report a case of epithelioid haemangioendothelioma involving both lung and liver. The tumour cells were positive for factor-VIII-related antigen. Immunohistochemical analysis of various basement membrane components in tumour tissue of lung and liver showed striking differences. In the liver tumour there was selective expression of collagen IV, with minimal and focal amounts of laminin and basement membrane-associated heparan sulphate proteoglycan. In the lung tumour nodules, in contrast, all these basement membrane components were present. These patterns of basement membrane expression closely resemble those of normal liver and lung basement membrane respectively. We suggest that this provides evidence that epithelioid haemangioendothelioma arises from local endothelial cell proliferation and that it supports the assumption of a multicentric rather than metastatic origin when multiple tumour deposits are found.     

Current status of small peripheral adenocarcinomas of the lung and their importance to pathologists

There has been a large amount of work done recently on small peripheral stage I adenocarcinomas that come to resection. Radiological (including proportion of ground glass opacity) and pathological features of these lesions (predominant bronchioloalveolar component, central scar with or without invasion <0.5 cm) have been shown to be prognostically favorable with cure rate approaching 100% in some series. Most of these studies emanate from Japan. The relevance of these studies to other parts of the world, particularly North America, is discussed in light of the fact that some recent chemotherapeutic studies with gefitinib have shown increased response in individuals of Asian origin, suggesting that some genetic differences may be significant. The relevance of these findings to pathologists and the pathological study of small peripheral adenocarcinomas from elsewhere in the world are discussed.     

Ossification of the N-methyl-N'-nitro-N-nitrosoguanidine-induced small intestine adenocarcinomas in rats.

Eighty rats out of 233 developed malignant tumors in the stomach and small intestine by administration of 100 micrograms/ml N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 28 weeks. Fifteen lesions (30%) among the 50 small intestinal carcinomas showed ossification in the tumor, while none in the sarcomas (12 lesions) or gastric adenocarcinomas (59 lesions) showed ossification. Multifocal heterotopic bone formation was found within stroma in close approximation to the neoplastic glands. The islands of bone trabeculae were covered by osteoblast-like cells, and abundant fibroblasts in loose stroma gathered around the bony islands which enclosed osteocytes in lacunae. Neither osteoclast nor cartilage was identified. In 5 cases, ossification was extensive, which comprised the major portion of the stroma. In contrast, intraluminal calcification without ossified foci were occasionally seen in the gastric carcinoma. Ossification of the intestinal tumors correlated to the degree of mucin content (p < 0.05, chi square with Yates' correction), degree of neutrophilic infiltration (p < 0.05), and size of the tumor (p < 0.1). (The average size of the ossified tumor was 21.5 +/- 4.0 mm, while that of nonossified tumors was 12.5 +/- 1.9 mm). The degree of tumoral necrosis, desmoplasia or depth of invasion did not seem to be related to the ossification of the tumor. The ossification rate of this experimental model was much higher than in human cases. Various histologic alterations, such as mucin leakage, inflammatory cell infiltration, necrosis and/or fibrosis, which might be caused by continuous stimulation of the strong carcinogen, may play some role in the ossification of experimental tumors.