MAGE-C2/CT10 Protein Expression Is an Independent Predictor of Recurrence in Prostate Cancer

The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity) and castration-resistant prostate cancer (17% positivity; p<0.001). Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015), which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05). MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer

Immunohistochemical analysis of the expression of MAGE-A and NY-ESO-1 cancer/testis antigens in diffuse large B-cell testicular lymphoma

BACKGROUND: Primary testicular lymphoma (PTL) is a rare and lethal disease. The most common histological subtype is diffuse large B-cell lymphoma (DLBCL). Standard treatments are frequently ineffective. Thus, the development of novel forms of therapy is urgently required. Specific immunotherapy generating immune responses directed against antigen predominantly expressed by cancer cells such as cancer-testis antigens (CTA) may provide a valid alternative treatment for patients bearing PTL, alone or in combination with current therapies. METHODS: Three monoclonal antibodies (mAbs), 77B recognizing MAGE-A1, 57B recognizing an epitope shared by multiple MAGE-A CTA (multi-MAGE-A specific) and D8.38 recognizing NY-ESO-1/LAGE-1 were used for immunohistochemical staining of 27 PTL, including 24 DLBCL. RESULTS: Expression of MAGE-A1 was infrequently detectable in DLBCL specimens (12.50%), whereas multi-MAGE-A and NY-ESO-1/LAGE-1 specific reagents stained the cytoplasms of tumor cells in DLBCL specimens with higher frequencies (54.17% and 37.50%, respectively) with different expression levels. CONCLUSIONS: These results suggest that MAGE-A and NY-ESO-1/LAGE-1, possibly in combination with other CTA, might be used as targets for specific immunotherapy in DLBCL

Outcome after renal transplantation in a "senior" program: the croatian experience

BACKGROUND: The Eurotransplant "senior" program allocates kidneys from elderly donors to patients >65 years old. It aims to increase the number of renal transplantations. Kidneys are allocated locally without human leukocyte antigen (HLA) matching to decrease the cold ischemia time. Croatia has introduced its own "senior" program based on HLA matching. We compared results with those from Eurotransplant. ----- METHODS: We identified and prospectively followed all patients aged of >/=65 years who underwent a first renal transplantation. We recorded their HLA matching, cold ischemia time, renal function, surgical and medical complications, and duration of hospitalization. ----- RESULTS: Through October 2007, 22 elderly patients received an allograft from donors who were >65 years old. There were 8 female and 14 male patients of mean age at transplantation of 67.4 years. Mean donor age was 66 years. The number of HLA mismatches ranged from 1 to 5, and cold ischemia time from 7 to 15 hours. One-year patient survival was 95.4%, and graft survival was 81.8%. Delayed graft function, defined as the need for dialysis for >7 days after transplantation, occurred in 63.6% of patients. Older recipients required prolonged hospitalization after transplantation (45 days; range, 16-131). Frequent posttransplant complications included posttransplant diabetes mellitus in 1 patient, delayed wound healing in 5 patients, and lymphocoel in 2 patients. Maligancies occurred in 3 patients, neoplasm of the native kidney, posttransplant lymphoproliferative disease, and skin cancer. One patient experienced acute rejection that was successfully treated with steroids. Seventeen patients experienced 20 viral infections. There was only 1 serious infection (pulmonary tuberculosis). The major problems were cardiovascular complications which occurred in 40.9% of patients. ----- CONCLUSION: Renal transplantation in elderly patients is associated with increased incidence of posttransplant surgical and medical complications which demand prolonged hospitalization. Incidence of acute rejections in elderly patients is significantly decreased with HLA matching, without prolongation of the cold ischemia time. Good results justify renal transplantation in this group of patients