lactoferrin and Metaplasia

Early diagnosis and curative resection are the predominant factors associated with increased survival in patients with gastric cancer. However, most gastric cancer cases are still diagnosed at later stages. Since most pathologic specimens are archived as FFPE samples, the ability to use them to generate expression profiles can greatly improve cancer biomarker discovery. We sought to uncover new biomarkers for stomach preneoplastic metaplasias and neoplastic lesions by generating proteome profiles using FFPE samples. We combined peptide isoelectric focusing and liquid chromatography-tandem mass spectrometry analysis to generate proteomic profiles from FFPE samples of intestinal-type gastric cancer, metaplasia, and normal mucosa. The expression patterns of selected proteins were analyzed by immunostaining first in single tissue sections from normal stomach, metaplasia, and gastric cancer and later in larger tissue array cohorts. We detected 60 proteins up-regulated and 87 proteins down-regulated during the progression from normal mucosa to metaplasia to gastric cancer. Two of the up-regulated proteins, LTF and DMBT1, were validated as specific markers for spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia, respectively. In cancers, significantly lower levels of DMBT1 or LTF correlated with more advanced disease and worse prognosis. Thus, proteomic profiling using FFPE samples has led to the identification of two novel markers for stomach metaplasias and gastric cancer prognosis.

Topics: Biomarkers, Tumor; Calcium-Binding Proteins; Cell Lineage; Clusterin; Disease Progression; DNA-Binding Proteins; Gastric Mucosa; Humans; Intercellular Signaling Peptides and Proteins; Lactoferrin; Metaplasia; Models, Biological; Neoplasm Proteins; Neoplasm Staging; Paraffin Embedding; Peptides; Proteomics; Receptors, Cell Surface; Stomach; Stomach Neoplasms; Trefoil Factor-2; Tumor Suppressor Proteins; Up-Regulation

Three cases of adenomatoid odontogenic tumour (AOT) were examined by morphological and immunohistochemical methods, to define the nature of tumour cells and to determine the correlation between the occurrence of extracellular eosinophilic amorphous material and epithelial tumour cells. The epithelial tumour cell components observed in this study were divided into three cell types (cell type I: small compact cells in a solid nodule and pseudoglandular cells in a duct-like structure; cell type II: peripheral elongated cells and spindle-shaped cells in a cribriform pattern; and cell type III: metaplastic squamous cells). The mesenchymal components consisted of eosinophilic amorphous material and calcified material. Immunohistochemically, the type I cells reacted positively with antibodies to transferrin, ferritin and alpha-one-antitrypsin (alpha1-AT), whereas the type II cells constantly indicated intense expression only for transferrin and alpha1-AT. All types of epithelial tumour cells reacted negatively with lactoferrin, alpha-one-antichymotrypsin, S-100 protein, S-100alpha subunit and S-100beta subunit. Moreover, the eosinophilic amorphous material and calcified material examined were positive for the antibody against alpha1-AT. These materials expressed immunophenotypes similar to those of the epithelial tumour cells, except for metaplastic squamous cells. The present study showed that iron-binding proteins and proteinase inhibitor might be related to the pathogenesis of AOT. Furthermore, we indicated that the formation of eosinophilic amorphous material was associated with type I and type II cells.

Topics: Adolescent; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Calcium-Binding Proteins; Carrier Proteins; Child; Epithelial Cells; Female; Ferritins; Humans; Immunohistochemistry; Immunophenotyping; Iron-Binding Proteins; Lactoferrin; Male; Mandibular Neoplasms; Maxillary Neoplasms; Mesoderm; Metaplasia; Nerve Growth Factors; Odontogenic Tumors; Protease Inhibitors; Receptors, Transferrin; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Transferrin; Transferrin-Binding Proteins

Topics: Animals; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Cytodiagnosis; Gastric Mucosa; Immunoenzyme Techniques; Intestinal Mucosa; Lactoferrin; Metaplasia; Muramidase; Serous Membrane

A total of 238 randomly selected gastric biopsies were examined with polyclonal antibodies from rabbits (antihuman-lysozyme and antihuman-lactoferrin) using the Peroxidase-Antiperoxidase-method according to Sternberger. The preparations were evaluated by comparing the intensity of the staining as well as the quantity and distribution of positive cells within the mucosa. The results show that lysozyme can be demonstrated constantly in the glandular neck zone and in the mucoid glandular body within the normal non-inflamed mucosa of the antrum, whereas in the normal corpus mucosa only a small amount of lysozyme appears focally and inconsistently in the neck area of the glands. A substantial increase in the intensity of lysozyme presentation due to inflammatory changes as related to the chronic superficial gastritis of the antrum cannot be discovered. On the contrary, the presentable amount of lysozyme decreases in line with the progressing inflammation and, in case of chronic-atrophic gastritis with intestinal metaplasia is restricted to the Paneth cells. A distinct and constant presentation of lysozyme can be achieved in the glandular neck zone, in the lower gastric pits and partially in the upper glandular body of the corpus mucosa in cases of chronic inflammatory processes. Obviously lysozyme is formed in the epithelial cells and not taken up from other cells. Furthermore it can be concluded from the findings that to a large extent lysozyme formation is linked to the proliferation activity of the epithelial cells. Lactoferrin cannot be found in normal non-inflammatory mucosa neither of the antrum nor of the corpus. But it can be found among most of the biopsy specimens with inflammatory changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Campylobacter Infections; Female; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Granulocytes; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Male; Metaplasia; Middle Aged; Muramidase

Epithelial distributions of immunoglobulin A, secretory component, lysozyme, and lactoferrin were studied by paired immunofluorescence staining in ethanol-fixed biopsy specimens from gastric antral and body mucosa. Fluorescence scores were assigned semiquantitatively for the epithelium in three mucosal zones (foveolar, isthmus, and glandular). In each case, degree of inflammation was graded blindly after conventional histologic staining of serial sections. The results showed that the overall epithelial expression of local defense factors was significantly enhanced in association with gastritis, both with regard to nonspecific antimicrobial substances (lysozyme and lactoferrin) and the external transfer of immunoglobulin A (mediated by secretory component) as a potential carrier of protective antibodies. The antral isthmus and glandular zones were most active in both respects. Despite the expression of relatively large amounts of epithelial immunoglobulin A and secretory component in metaplastic glands, these elements lacked the nonspecific defense factors (except for lysozyme in Paneth cells)--even when they occurred in the antral mucosa--and may, therefore, represent particularly vulnerable areas.

Topics: Adult; Aged; Female; Fluorescent Antibody Technique; Gastric Mucosa; Gastritis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Lactoferrin; Lactoglobulins; Male; Metaplasia; Middle Aged; Muramidase; Secretory Component; Staining and Labeling