cefoxitin and Carcinoma--Transitional-Cell

The tumor-associated Tn antigen has been investigated extensively as a biomarker and therapeutic target. Cancer vaccines containing the Tn antigen as a single tumor antigen or as a component of a polyvalent vaccine have progressed into phase I and II clinical trials. One major focus of Tn-based vaccines is the treatment of prostate cancer patients. Although expression of the antigen on prostate tumors is a critical prerequisite, previous reports investigating Tn expression in prostate tumors have produced conflicting results. Using a combination of immunohistochemistry and carbohydrate microarray profiling, we show that only 4% to 26% of prostate tumors express the Tn antigen. Based on our results, the majority of prostate cancer patients do not express the appropriate antigen. Therefore, efforts to preselect the subset of prostate cancer patients with Tn-positive tumors or apply Tn vaccines to other cancers with higher rates of antigen expression could significantly improve clinical response rates. Because conflicting information on carbohydrate expression is a general problem for the field, the approach described in this article of analyzing antigen expression with multiple antibodies and using carbohydrate microarray profiles to interpret the results will be useful for the development of other carbohydrate-based cancer vaccines and diagnostics.

Topics: Adenocarcinoma; Aged; Animals; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Cancer Vaccines; Carbohydrates; Carcinoma, Transitional Cell; Clinical Trials as Topic; Humans; Hyperplasia; Male; Prostatic Neoplasms; Rabbits

To study the effectiveness of combining DNA ploidy and the blood-group related membrane antigen Tn as bladder tumour markers which have been individually associated with high tumour grade and poor prognosis. In particular to (i) determine whether use of these two markers would improve tumour detection compared with either alone, particularly of high grade disease and (ii) determine whether intermediate rates of marker expression would occur in bladder cancer patients with no current tumour compared with those with a tumour and a control group with benign prostatic hypertrophy.. A total of 102 patients undergoing cystoscopic monitoring for either benign prostatic hyperplasia (BPH) or for transitional cell carcinoma (TCC) at the Repatriation Hospital and Flinders Medical Centre were included in the study. The patients comprised three study groups, those with BPH (n = 37), with TCC but no tumour present (n = 38) and those with TCC and a tumour present at cystoscopy (n = 27). Exfoliated cells obtained from bladder washings at cystoscopy were double-labelled using a monoclonal antibody to the Tn antigen and a DNA stain, propidium iodide and examined by flow cytometry.. Rates of marker expression in 27 patients with tumours were 30% for Tn antigen, 30% for aneuploidy and 48% for either marker. Marker expression was strongly associated with tumour grade, with no expression at grade 1, 38% (3/8) tumours at grade 2 and 90% (9/10) at grade 3. In patients with a history of bladder tumours but no current tumour, rates were intermediate (30%) compared with patients with current transitional cell carcinoma (42%) and control patients (19%).. The use of Tn antigen combined with DNA flow cytometry can increase tumour detection, particularly of high grade, aggressive disease. Gradation of expression of these markers across patient groups at increasing risk of a tumour, with intermediate expression in patients with no current tumour, suggests that marker expression may be detecting a preneoplastic stage of the disease, which is not possible with cytology. Given two parallel disease processes for superficial papillary and for high grade disease with invasive potential, the expression of high grade tumour markers in cells from cystoscopically normal bladders may represent a pre-clinical stage of aggressive disease. The identification of patients at risk of invasive disease using combinations of tumour markers may offer advantages in clinical management, particularly when no tumour is present and therefore no histopathological assessment is made.

Topics: Aged; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Transitional Cell; Female; Flow Cytometry; Genetic Markers; Humans; Male; Ploidies; Urinary Bladder Neoplasms

The T-antigen system and the mean nuclear volume have been proposed as risk variables in bladder tumors. This study includes 34 patients with initially noninvasive (Ta) transitional cell carcinomas who experienced different courses of disease. Tissue specimens of primary tumors were analyzed for the expression of T-antigen, Tn-antigen, and sialosyl-Tn-antigen using monoclonal antibodies (MoAb) and the lectin peanut agglutinin (PNA) in an indirect immunoperoxidase method. In addition, the mean nuclear volume was estimated by morphometry. Tissue from 7 of 13 patients (54%) who had invasive disease during a follow-up period of 5 years expressed T-antigen, as defined by MoAb HH8 in the primary tumor, whereas tissue of only 3 of 21 patients who did not have invasive disease expressed the antigen (P less than 0.02). No association was found between tumor progression to invasion and the expression of Tn-antigen or sialosyl-Tn-antigen. Tn-antigen expression was partially lost in invasive tumors (P less than 0.03) when compared with the expression in primary noninvasive tumors. A high mean nuclear volume in tissue specimens of primary tumors correlated with a progression to invasive disease (P less than 0.01). A significantly (P less than 0.003) higher mean nuclear volume was found in tumor areas that were positive for PNA compared with areas that were negative for PNA in primary tumors. A significantly lower mean nuclear volume was found in Tn-antigen-positive invasive Grade 3 tumor areas than in Tn-antigen-negative areas (P less than 0.005). The combined use of T-antigen expression and mean nuclear volume is of potential clinical interest for determining patients who are at high risk of disease progression.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Transitional Cell; Cell Nucleus; Disaccharides; Humans; Immunoenzyme Techniques; Middle Aged; Neoplasm Recurrence, Local; Predictive Value of Tests; Urinary Bladder Neoplasms