lewis-x-antigen and Carcinoma--Small-Cell

Serum tumor markers are non-invasive diagnostic tools for malignant tumor and commonly used for screening of cancer and as an indicator of treatment-effect. In small cell lung cancer, NSE and proGRP are effective markers. In non-small cell lung cancer (NSCLC), CEA, SCC, CYFRA21-1, SLX and CA19-9 are commonly used for screening, and at least one marker among CEA, SCC or CYFRA21-1 is positive in 77% of patients with NSCLC. According to the histological type, the positive rate of CEA and CYFRA21-1 is high in adenocarcinoma patients, and the positive rate of CYFRA21-1 and SCC is high in squamous cell carcinoma patients. This review summarizes the clinical usefulness of tumor markers in primary lung cancer.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Humans; Keratin-19; Keratins; Lewis X Antigen; Lung Neoplasms; Peptide Fragments; Peptides; Recombinant Proteins; Serpins

Changes in cell membrane carbohydrate antigens play an important role in metastatic potential associated with carcinogenesis and in prognostic factors. We investigated immunohistochemically the expression of CD15 and sialyl CD15 (sCD15) in lung cancer tissue by using Leu-M1 antibody and MXKM-93 antibody, respectively, and then assessed the relationship between their expression and the patient outcome. Lung cancer tissue expression of CD15 was significantly higher in adenocarcinoma (55.9%) and squamous cell carcinoma (44.7%) than in small cell carcinoma (10%) (p=0.01, p=0.006). Expression of sCD15 was significantly higher in adenocarcinoma (52.9%) than in squamous cell carcinoma (10.5%) or small cell carcinoma (10%) (p<0. 0001, p=0.016). No association was found between CD15 expression and clinical stage, but sCD15 expression increased with clinical stage (stage I+II vs. III+IV: 16.7% vs. 39.6%; p=0.049). Expression of CD15 (1.5%) was significantly lower than expression of sCD15 (12.3%) in normal surrounding tissue. Examination of associations with outcome in NSCLC revealed that expression of sCD15 in resected cases, and expression of CD15 in non-resected cases were significantly correlated with shortening of median survival time (p<0.05). When associations with prognostic factors were assessed by univariate analysis, expression of sCD15 was found to be correlated with distant metastasis, and expression of CD15 with decrease in performance status (PS). In the multivariate analysis by the Cox proportional hazard model, sCD15 and CD15 negativity contributed to longer survival time after PS and clinical stage. The results of a combination assay of CD15 and sCD15 showed that expression of both carbohydrate antigens significantly shortened survival time in both the resected and non-resected group (log-rank test, p<0.05). This combination assay also appeared to be extremely useful in predicting the outcome in all clinical stages of NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease Progression; Female; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oligosaccharides; Prognosis; Rabbits; Risk Factors; Sialyl Lewis X Antigen; Survival Analysis

One hundred and five cases of various human lung neoplasms were studied immunohistochemically using monoclonal antibodies recognizing the antigens, Le(x), sialylated Le(x) (SLEX), Le(a), and sialylated Le(a) (SLEA). Of the 92 lung cancers examined for antigen expression SLEX was detected in 57% (52 cases), Le(x) in 42% (39), SLEA in 36% (33), and Le(a) in 23% (21). None of these antigens were expressed in 9 tumor like lesions of the lung or the 4 other non-epithelial malignant lung tumors examined. Higher expression was seen in the 54 lung adenocarcinomas: SLEX in 72%, Le(x) in 48%, SLEA in 39%, and Le(a) in 24%. The type 2 carbohydrate antigens (SLEX and Le(x) were more prevalent than the type 1 antigens (SLEA and Le(a)) in lung adenocarcinoma tissues. In adenocarcinomas, SLEX was expressed in 71% (10/14) of the Le(b) patients, and in 100% (5/5) of the Le(a) patients. Unexpectedly, SLEX was not detected in 4 out of 5 Le(a-b-) patients tested. This suggests that the expression of the Le(x) antigens and the Le(a) antigens are related in lung adenocarcinoma. These antigens were less expressed in other types of lung cancers. Tissue sections obtained serially showed heterogeneity in the expression of these antigens, as evidenced by the concurrent presence of both SLEX and SLEA. These results indicate that SLEX is a useful tumor-associated marker for lung adenocarcinomas, and that terminal fucosylation and sialylation may be activated heterogeneously in these lung cancers.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Blood Group Antigens; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Differentiation; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lung Neoplasms; N-Acetylneuraminic Acid; Sialic Acids

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

Serum SLX, CEA, SCC and NSE levels were serially measured in 266 patients with lung cancer and compared with those in 345 patients with benign respiratory disorders (BRD). The positive rate for CEA in lung cancer (44.4%) and the false-positive rate in BRD (15.3%) were the highest among the 4 markers. The positive rate for SLX in lung cancer (32.0%) was lower than that of CEA, while the false-positive rate for SLX in BRD (7.2%) was lower than that of CEA. The positive rate for SLX was highest in adenocarcinoma and correlated better with the clinical stages than did CEA. SCC and NSE were specifically elevated in squamous cell carcinoma and small cell carcinoma, respectively. Using these 4 markers, only 70.2% of patients were correctly diagnosed as having lung cancer or BRD. In monitoring treatment effect, only SLX showed a statistically significant correlation with regression and progression in adenocarcinoma, while NSE and SLX showed such a correlation in small cell carcinoma. Serum tumor markers seem to be less sensitive for the diagnosis of lung cancer than chest X-ray and sputum cytology, indicating that a search for more specific markers is still required. However, in monitoring treatment effect, SLX appeared to be suitable for adenocarcinoma, while NSE and SLX seemed to be useful in small cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Serpins

The clinical significance of tumor-associated glycosylated antigen, sialylated Lewisx (SLEX) was demonstrated with reference to pulmonary diseases by fluorescent enzyme immunoassay. In benign lung diseases 5.5% were positive for serum SLEX. Lung cancer, the highest percentage positivity was seen in adenocarcinoma (41.7%), and clinical stage III and IV showed 36.2% and 41.9%, respectively. These results indicate that SLEX might conceivably be useful as a tumor marker, particularly for adenocarcinoma of the lung. Using Sephacryl S-1000 columns the elution profiles of sera and bronchoalveolar lavage in cases of lung cancer, gastric cancer and diffuse panbronchiolitis were also investigated, and it was concluded that the release mechanism of the antigen into blood stream in the malignant diseases is different from that in benign disease and the carrier protein binding to the antigen varies according to the disease.

Topics: Adenocarcinoma; Adult; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

Stage-specific embryonic antigen-1 (SLX) is a glycolipid recognized by a monoclonal antibody (FH 6) which is produced by cells immunized with mice teratocarcinoma cell line. Using an SLX (Otsuka) kit from Ostuka Assay Laboratory, we measured the serum level of SLX in 96 patients with lung cancer, 305 patients with non-cancerous lung disease and 86 healthy adults, prospectively. When we adopted a cutoff level of 42U/ml (mean + 2S.D. in the healthy adults), the overall positive rates were 29.2% in the lung cancer patients, 15.1% in the non-cancerous patients and 0% in the healthy adults. The positive rate of the lung cancer patients was significantly higher than in the patients with non-cancerous lung disease (p less than 0.05). According to the histological type of lung cancer, the positive rates were 40.9% in 44 patients with adenocarcinoma, 18.4% in 37 patients with squamous cell carcinoma, 0% in 7 patients with small cell carcinoma, and 0% in 3 patients with large cell carcinoma. Staging of the lung cancer patients revealed positive rates for serum SLX of 5.6% in 18 stage I patients, 22.2% in 9 stage II patients, 33.3% in 21 stage IIIA patients, 33.3% in 27 stage IIIB patients, 42.9% in 21 stage IV patients. After we performed the immunostaining method for SLX using FH6, positive immunoactivity was demonstrated mainly in the cell membrane of adenocarcinoma cells. SLX seems to be a tumor-associated marker in patients with lung adenocarcinoma.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Reference Values

Serum levels of sialylated Lewisx (SLEX) and sialylated SSEA-1 (S-Xi) in 136 cases of diagnosed lung cancer (63 adenocarcinoma, 45 squamous cell carcinoma, 20 small cell carcinoma and 8 large cell carcinoma) and 111 cases of benign pulmonary disease were measured. The positive rate of these markers in the primary lung cancer group was significantly higher than those in benign pulmonary diseases. The positive rates of serum SLEX and S-Xi in all lung cancer cases were 27.2% and 27.9%, respectively. The antigen levels in the sera were higher in adenocarcinoma as compared to other histologic types, and increased as the stage advanced. It was concluded that SLEX and S-Xi are very useful markers of lung cancer for diagnosis and monitoring the clinical status.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Gangliosides; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms

The clinical significance of serum sialyl SSEA-1 antigen was evaluated using the sera of 1261 patients with malignant tumors and 717 patients with non-malignant diseases measured with Otsuka Assay Laboratories' RIA Kits. The results indicate that the antigen was frequently elevated in the sera from the patients with various adenocarcinomas, including lung (45%), pancreas (64%) and ovary (57%). The false positive incidence of antigens in the sera from the patients with non-malignant disorders was as low as 4.9%. No correlation was observed with other tumor markers examined in this study, and the diagnostic efficiency increased significantly by the combined determination of sialyl SSEA-1 antigen level with other markers. The serial determination of the serum sialyl SSEA-1 antigen level has a clinical utility also in monitoring the patients with adenocarcinoma receiving surgical operation and/or chemotherapy as indicated by the results of the longitudinal observation of the patients.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Gastrointestinal Neoplasms; Glycolipids; Humans; Lewis X Antigen; Lung Diseases; Lung Neoplasms; Male; Radioimmunoassay; Reagent Kits, Diagnostic

Bronchopulmonary carcinomas were analyzed immunohistochemically using monoclonal antibody 624A12. The antibody was raised against a human "small cell carcinoma" cell line NCI-H69. It recognizes a particular sugar sequence in lacto-N-fucopentose III, which is preserved in formalin fixed and paraffin embedded tissue. Various bronchopulmonary carcinomas revealed characteristic patterns of immunoreactivity. Forty nine/50 adenocarcinomas were immunoreactive either diffusely or focally. The immunostaining was usually limited to the cell membranes with occasional intracytoplasmic immunostaining in large cells. The only negative case had been irradiated before surgical resection. Twenty seven/38 squamous cells carcinomas did not immunostain while the remaining 11 displayed focal immunoreactivity in areas of "loose cellular apposition" associated with necrosis and, rarely, in squamous pearls. All of six adenosquamous carcinomas showed immunoreactivity focally. Eleven/30 large cell carcinomas and 10/11 bronchiolo-alveolar carcinomas were either diffusely or focally immunoreactive. Seven/26 intermediate cell neuroendocrine carcinomas were focally immunoreactive while none of 33 typical small cell neuroendocrine carcinomas, 21 carcinoids, and 10 well differentiated neuroendocrine carcinomas was immunoreactive. An adenoid cystic carcinoma was diffusely immunoreactive, and a mucoepidermoid carcinoma was focally immunoreactive. We conclude that various bronchopulmonary neoplasms have characteristic patterns of distribution of this antigen, and that monoclonal antibody 624A12 may be useful for the differential diagnose among bronchopulmonary carcinomas, and their differential diagnosis from pleural mesotheliomas.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Animals; Antibodies, Monoclonal; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Line; Humans; Lewis X Antigen; Lung Neoplasms; Mice; Mice, Nude; Oligosaccharides