lewis-x-antigen and Precancerous-Conditions

Surgical specimens of 7 cases of bronchioalveolar carcinoma complicated with pulmonary fibrosis and 4 cases of simple pulmonary fibrosis were examined histopathologically and immunohistochemically. The morphology and histogenesis of adenomatous hyperplasia (AH) of alveolar epithelium and its relation to bronchioalveolar carcinoma were investigated. The AH was classified as types I and II according to their microscopic morphologic characteristics. In this group, 6 cases of type I-AH and 5 cases of type II-AH were observed. The results of anti-SA, anti-SSEA-1 and anti-CEA monoclonal antibody examinations indicate that AH is a nonspecific hyperplastic lesion of alveolar epithelium occurred during chronic pulmonary inflammatory diseases. Both type I and II AH originated from type B alveolar epithelial cells. The latter developed on the basis of the former, but with a more immature tendency and hyperplastic potential, being a pre-malignant alteration. It could be considered that certain cases of bronchioalveolar carcinoma are originated from type B alveolar epithelial cells, some of which underwent malignant change from type II alveolar hyperplasia.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Aged; Apoproteins; Carcinoembryonic Antigen; Epithelium; Female; Humans; Hyperplasia; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Precancerous Conditions; Pulmonary Alveoli; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants

The present study aimed to determine significance of E-cadherin, a cell adhesion molecule, and sialyl Lewis-X (sLeX), a cell surface antigen, in oral carcinogenesis. Expressions of E-cadherin and sLeX were detected using western blot analysis from oral malignant (n=25), and oral precancerous tissues (OPC, n=20) and their adjacent normal tissues. An altered expression of E-cadherin (E-cad) and sLeX was observed in malignant and precancerous tissues. E-cad western blot revealed presence of two bands, a 120 kDa (native, E-cad120) and a 97 kDa (known as truncated E-cad97). The accumulation of truncated E-cad97 and sLeX in malignant and OPC tissues compared to their adjacent normal tissues was observed. Receiver's Operating Characteristics (ROC) curve analysis showed good discriminatory efficacy of E-cad97, E-cad97:120 ratio and sLeX between the malignant and adjacent. normal tissues. Further, a positive correlation of E-cad97 and sLeX overexpression with advanced stage of the disease and lymphnode metastasis was observed. The data suggest that E-cadherin truncation and sLeX overexpression are early events which may facilitate the tumor cells to metastasize. Also, overexpression E-cad97 and sLeX in OPC tissues may be useful to predict metastatic potentials of tumors at an early stage of oral carcinogenesis. Key words: Oral cancer, oral precancerous conditions, E-cadherin, sialyl Lewis-X, metastasis.

Topics: Adult; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Blotting, Western; Cadherins; Carcinoma, Squamous Cell; Humans; Lewis X Antigen; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Protein Processing, Post-Translational; ROC Curve; Sialyl Lewis X Antigen

Mucins and mucin-associated carbohydrates have a distinct expression pattern that can be modified under pathological conditions. Normal gastric mucosa expresses MUC1 and MUC5AC in foveolar epithelium and MUC6 in the glands. Lewis type-1 chain antigens (Le(a) and Le(b)) are expressed in foveolar epithelium, whereas Lewis type-2 chain antigens (Le(x) and Le(y)) are expressed in the glands. In this study we used monoclonal antibodies to evaluate the pattern of mucins and Lewis type-1 carbohydrates in intestinal metaplasia (IM) and compared it with IM types determined using histochemistry. In type-I or complete IM we found expression of MUC2 intestinal mucin and decreased/absent expression of MUC1, MUC5AC and MUC6. In type-II/III or incomplete IM there was co-expression of MUC2 and the mucins expressed in the stomach. No major differences were detected among the three IM types regarding expression of Lewis antigens. Furthermore we observed that sialylated compounds other than sialyl-Le(a) are responsible for histochemical detection of sialomucins and that sulpho-Le(a/c) is expressed in the presence or absence of sulphomucins detected using histochemistry. We conclude that mucin immunohistochemistry may replace classic histochemistry for the classification of IM into complete and incomplete types. The present study challenges the distinction of type-II from type-III IM since we did not observe major differences in the expression profile of mucins and Lewis type-1 carbohydrates. Finally, it seems necessary to evaluate the predictive value of IM according to the presence of specific sulphated carbohydrates (e.g. sulpho-Le(a/c)) rather than histochemically detected sulphomucins.

Topics: Carcinoma; Gastric Mucosa; Gastroscopy; Humans; Immunoenzyme Techniques; Intestines; Lewis X Antigen; Metaplasia; Mucins; Precancerous Conditions; Stomach; Stomach Neoplasms

Fifty esophageal adenocarcinomas were investigated for their expression of Le(a), Le(x), and Le(a)-Le(x). Among the 50 adenocarcinomas, 17 cases developed in Barrett's epithelium. Those 17 differed from the other 33 cases by expressing much less Le(x). Fifty-nine percent of Barrett's adenocarcinomas were Le(x) negative compared with 24% of the non-Barrett's carcinomas. All Barrett's adenocarcinomas showed less than 50% Le(x) whereas 50% of non-Barrett's carcinomas showed between 50 and 100% expression. The statistical correlation coefficient for this association was P < 0.001. Normal gastric cardia epithelium showed the same Le(x) expression in both groups. In the Barrett group, Le(x) expression decreased from normal through intestinal metaplasia and dysplasia to adenocarcinoma. This progression was not seen in the non-Barrett group. Loss of Le(x) expression may prove useful in following patients with Barrett's epithelium in evaluating progression toward a malignant process. No difference in expression of Le(a) and Le(a)-Le(x) was found between Barrett's and non-Barrett's carcinomas.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Cell Transformation, Neoplastic; Epithelium; Esophageal Neoplasms; Esophagus; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Lewis X Antigen; Male; Middle Aged; Precancerous Conditions; Prognosis

Monoclonal antibody AM-3 (MAb AM-3) raised against a sialomucin from human colorectal carcinoma has previously been shown to define a carbohydrate epitope, which is detectable by immunocytochemistry on all investigated colonic carcinomas and is expressed in correlation with the grade of dysplasia in colonic adenomas (Hanski et al., J. Clin. Pathol., 43: 379-385, 1990). Epitope analyses in solid-phase enzyme immunoassays revealed that AM-3 antibody recognizes the sialylated Lewis(x) sequence on a branched O-linked glycan and its reductively cleaved alditol from human amniotic mucins. In comparative binding and binding inhibition studies MAbs AM-3 and CSLEX1 displayed reciprocal affinities to mucins versus gangliosides. Correspondingly, the weaker binding activities of AM-3 versus CSLEX to III3-alpha Fuc-IV3-alpha NeuAc-nLcOse4-Cer or to monogangliosides from human granulocytes were measured. Gangliosides from a human colon carcinoma were recognized by MAb CSLEX1 exhibiting a broader specificity to various sialyl-Lewis(x) antigens and by MAb FH6 reactive to sialyl-dimeric Lewis(x) antigen, but not by MAb AM-3. In conclusion, MAb AM-3 is distinguished from other sialyl Lewis(x)-specific MAbs by its selective reactivity to mucin-carried epitopes on the monomeric antigen.

Topics: Adenoma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Birds; Carbohydrate Sequence; Cattle; Colon; Colonic Neoplasms; Female; Humans; Lewis X Antigen; Milk, Human; Molecular Sequence Data; Mucins; Oligosaccharides; Pancreatic Neoplasms; Precancerous Conditions; Sheep

Topics: Adenocarcinoma; Antigens, Neoplasm; Colonic Neoplasms; Female; Fetus; Glycolipids; Humans; Intestinal Mucosa; Lewis X Antigen; Precancerous Conditions; Pregnancy