lewis-x-antigen and Adenocarcinoma--Mucinous

One of the most urgent requirements in breast cancer is the development of a blood-based test for early detection and prognosis. Previously published results found a significant difference between specific glycan levels in patients with advanced breast cancer and healthy controls. The aim of this investigation was to address a more clinically relevant problem, i.e., whether the measurement of specific glycans could identify women with aggressive disease at an early stage. In order to reduce potential bias in this study, blood samples from patients were collected, stored and analyzed in a similar manner. Agalactosyl biantennary glycans (FA2) and glycans containing the sialyl Lewis x epitope (A3F1G1 and A2F1G1) were measured using high throughput normal-phase high-performance liquid chromatography in combination with exoglycosidase digestions in sera from 52 patients with early breast cancer (21 with lymph node-negative and 20 with lymph node-positive disease) and 134 women with benign breast disease. The combined levels of the glycans were significantly higher in patients with lymph node metastases compared to women without these metastases. Lymph node status is the single most important determinant of survival in early stage breast cancer. As high levels of these glycans were associated with nodal metastases, their measurement may provide a new non-invasive approach to determining prognosis in women with newly diagnosed breast cancer.

Topics: Adenocarcinoma, Mucinous; Axilla; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chromatography, High Pressure Liquid; Female; Humans; Lewis X Antigen; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Polysaccharides; Prognosis; Sialyl Lewis X Antigen

Mucinous tubular and spindle cell carcinoma is a rare and newly described type of renal cell carcinoma (RCC) with a relatively indolent behavior. However, its histogenetic origin or line of differentiation remains unclear. Twelve cases of mucinous tubular and spindle cell carcinoma were identified and retrieved from the files of 3 institutions. Detailed morphological features, as well as their immunohistochemical profile established with markers of proximal renal tubules (RCC marker antigen, CD15, and alpha-methylacyl-CoA racemase) and of distal renal tubules (kidney-specific cadherin and cytokeratin 7), were studied. The age range of the patients was 35 to 73 years with a median of 56 years. The male to female ratio was 1:3. All of the patients were alive with follow-up between 4 and 38 months. All the tumors were confined to the kidney with a mean tumor size of 6.9 cm (range, 1.8-17 cm). The tumors were composed of variable proportions of tubular and spindle cell areas with focal to prominent mucinous or myxoid stroma. Foamy macrophages were seen in 10 cases and were prominent in 4 cases. A focal compressed tubulopapillary growth pattern was seen in 10 cases. The tumor cells were uniformly cuboidal with ovoid to round nuclei and inconspicuous nucleoli (Furhman nuclear grade 3 in 6 cases). Focal necrosis was seen in 3 cases. Immunostains showed that tumors were positive for RCC marker antigen (11/12), alpha-methylacyl-CoA racemase (11/12), CD15 (8/12), CD10 (2/12), kidney-specific cadherin (1/12), and cytokeratin 7 (11/12). Its morphological features as well as a strong preferential expression of proximal tubule markers suggest that this tumor is a type of RCC with proximal tubular differentiation, which appears closely related to or represents a morphological variant of papillary RCC.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Cadherins; Carcinoma; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; Humans; Keratin-7; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Mitogen-Activated Protein Kinases; Necrosis; Neprilysin; Racemases and Epimerases

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.

Topics: Adenocarcinoma, Mucinous; Animals; Antibodies, Monoclonal; Apoptosis; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Nucleus; Cytoplasm; Gangliosides; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Injections, Subcutaneous; Kidney Neoplasms; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms, Experimental; Lung Neoplasms; Mice; Mice, Nude; Mucin-1; Mucins; Neoplasm Proteins; Neoplasm Transplantation; Neoplastic Stem Cells; Oligopeptides; Peptide Fragments; Phenotype; Sialyl Lewis X Antigen; Splenic Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured

We investigated immunohistochemically the localization of lysozyme and Leu M1 in normal skin, 76 cases of benign sweat gland tumors, 28 cases of malignant sweat gland tumors, 23 cases of extramammary Paget's disease, 7 cases of sebaceous carcinoma, 6 cases of malignant trichilemmoma, 10 cases of squamous cell carcinoma, and 10 cases of basal cell carcinoma and compared the results with those for gross cystic disease fluid protein (GCDFP)-15 to assess the sensitivity and specificity of our assay conditions for apocrine differentiation. Normal apocrine glands were stained with all three antibodies, while eccrine glands were positive only for GCDFP-15, and other portions of normal skin were not stained with any of the antibodies used. In neoplastic tissue thought to be from apocrine tumors, antibodies raised against lysozyme and GCDFP-15 had a greater specificity (100%) for apocrine differentiation, while Leu M1 had a greater sensitivity (88%). Tissues that were stained with two or three of these antibodies appeared to exhibit apocrine differentiation. In the tumors examined, the specificity for apocrine differentiation was 100% and the sensitivity for such differentiation was 92% by these criteria. According to these criteria, some cases of syringocystadenoma papilliferum, primary mucinous carcinoma of the skin, and extramammary Paget's disease with underlying adenocarcinoma showed apocrine differentiation.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenocarcinoma, Sebaceous; Adenoma, Sweat Gland; Adolescent; Adult; Aged; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carrier Proteins; Cell Differentiation; Eccrine Glands; Female; Glycoproteins; Humans; Immunohistochemistry; Lewis X Antigen; Male; Membrane Transport Proteins; Muramidase; Neoplasm Proteins; Neoplasms, Basal Cell; Paget Disease, Extramammary; Sensitivity and Specificity; Skin; Skin Neoplasms; Sweat Gland Neoplasms

A human colon cancer-derived cell line, KC-1, was established from the surgical specimen of mucinous adenocarcinoma of the colon. The cells grew as monolayers, showing formation of irregular aggregation of cells and pleomorphic nuclei. The doubling time in vitro was 56.6 hours. The cells produced CEA, CA19-9 and sialyl SSEA-1(SLX). Chromosome numbers were distributed between 79 and 83 with many structural abnormalities. A point mutation of the Ki-ras gene in codon 61 (CAA-->CAT) was found. The cells have been subcultured 13 times during these three years. This cell line can be useful for investigations of colon cancer.

Topics: Adenocarcinoma, Mucinous; Aged; CA-19-9 Antigen; Carcinoembryonic Antigen; Cell Line; Colonic Neoplasms; Female; Humans; Lewis X Antigen; Point Mutation

The immunohistochemical expression of sialylated and non-sialylated forms of both Le(x) and Le(a) were studied in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in 32 metastatic lymph nodes and 9 hepatic lesions, using an indirect immunoperoxidase staining. Their antigens were expressed in normal mucosa with the following frequencies: Le(a), 95.2% (40/42); sialyl Le(a), 88.1% (37/42); Le(x), 95.2% (40/42); and sialyl Le(x), 17.0% (7/42), whereas in carcinomas, the respective rate of frequency were: 78.2% (68/87); 78.2% (68/87); 90.8% (79/87); and 93.1% (81/87). Sialyl Le(x) antigen showed the highest tumor specificity compared to other antigens. In three normal mucosal specimens and four carcinomas with Le(a-b-) phenotype, the expression of type 1 antigens (Le(a) and sialyl Le(a)) was not consistent, whereas type 2 antigens (Le(x) and sialyl Le(x)) were consistently observed in carcinomas. The staining of type 1 antigens and Le(x) was decreased in metastatic lesions compared with primary carcinomas, whereas sialyl Le(x) antigen had the same positive-staining rate in both. Metastatic carcinoma expressed the sialylated form more predominantly than the non-sialylated form in type 2 antigens whereas the opposite result was observed in type 1 antigens. These results suggested that: (a) sialyl Le(x), defined by monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen in colorectal carcinoma, and (b) the alteration of Lewis-related carbohydrate antigens in cancer cell membranes, including sialylation and/or aberrant glycosylation, may be related to metastatic behavior.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Colorectal Neoplasms; Glycosylation; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis

The monoclonal antibodies C14 and C365 which define the Y hapten and specific carcinoembryonic antigen (CEA) were shown by ABC-immunohistochemical technique to stain positively the tissue sections in 48 of 56 cases (85.7%) of rectal carcinoma for Y hapten, in 51 cases (91%) for CEA, and 100% for both together. Cancer cells which expressed Y hapten were mainly distributed in the foreland and deep invading cancer tissue which showed high ability of malignant growth. Two patterns of localization on the cancer cells for Y hapten were found: local distribution in cytoplasmic Golgi region, similar to blood group antigens, and diffused distribution on the membrane and in the cytoplasm as CEA. Positive expression of Y hapten on the carcinoma associated with types of differentiation and Duke's pathology stages: highly expressed on the poorly differentiated cancer and in Duke's A and C stages (P less than 0.05). Phenotypes of Y hapten and CEA on metastatic cancer cells in lymph nodes and primary cancers were similar. Our findings indicate that the antibodies may be useful in immunodiagnosis and immunotherapy.

Topics: Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Carcinoembryonic Antigen; Carcinoma, Intraductal, Noninfiltrating; Humans; Immunohistochemistry; Lewis X Antigen; Rectal Neoplasms

The serum levels of sialyl SSEA-1 antigen, a type 2 chain carbohydrate antigen detected using the monoclonal antibody FH-6, were elevated in 47.2% of patients with epithelial ovarian cancer, with the percent positivity increasing with the clinical stage. Of the histological type, it is interesting to note the relatively high sensitivity in patients with mucinous adenocarcinoma and clear cell carcinoma in contrast with the CA 125 antigen levels. Although the percentage of patients with ovarian cancer who had elevated sialyl SSEA-1 antigen levels is lower than that observed with elevated CA 125 antigen levels, the false-positive rate is significantly low in the sialyl SSEA-1 test. Serial sialyl SSEA-1 antigen levels obtained during follow-up were strong predictors of clinical outcome. The combined determination possible with sialyl SSEA-1 and CA 125 did not markedly increase the detection rate because of the overlap in the positivity. However, increased levels of both serum sialyl SSEA-1 antigen and CA 125 antigen indicated the presence of malignancies in pregnant women associated with ovarian tumors.

Topics: Adenocarcinoma, Mucinous; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Cystadenocarcinoma; Female; Genital Diseases, Female; Humans; Lewis X Antigen; Ovarian Neoplasms; Pregnancy; Radioimmunoassay

The staining reactions of the monoclonal antibodies anti-EMA, AGF 4:48 and the lectin UEA-1 from Ulex europaeus were investigated in formalin-fixed, paraffin-embedded sections of 36 primary ovarian carcinomas. The staining patterns were graded and related to tumour type, differentiation, FIGO stage and patient survival. Both antibodies and UEA-1 showed variations in their staining between and within tumours. The staining of mucinous tumours using anti-EMA was significantly less than in non-mucinous tumours. No other significant associations were found between staining grade and the different variables under study. The variations in staining were not demonstrated to have any prognostic significance.

Topics: Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Female; Humans; Lectins; Lewis X Antigen; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; Plant Lectins; Staining and Labeling

Sialylated Lewis(x) and sialylated Lewis(a) antigens, which are structural isomer each other, were serologically tested to determine the clinicopathological differences and correlation between two antigens, and were also compared with those of serum CEA in 141 patients with gastric cancer. Percent positives in sialylated Lewis(a), CEA and sialylated Lewis(x) showed 26.9%, 21.8% and 17.0% respectively. Percent positive of sialylated Lewis(x) correlated with degree of liver metastasis and peritoneal dissemination. Therefore, it is emphasized that the role of sialylated Lewis(x) is characteristics of detecting a presence of liver metastasis and/or peritoneal dissemination. On the other hand, sialylated Lewis(a) showed high percent positive in cases which had lymph nodes metastasis and mucinous or papillary adenocarcinomas. These two carbohydrate antigens indicated no correlation (r = 0.062) in the spectrum of sera. It is suggested that combination assay of sialylated Lewis(x) and sialylated Lewis(a) is useful in detecting many gastric cancer patients including CEA-negative one.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma, Papillary; Glycolipids; Humans; Lewis X Antigen; Middle Aged; Stomach Neoplasms