Human Anti-Mouse TNFRSF11A monoclonal Antibody, clone SFB072 [APC]

Paget's disease of bone, although common in the United States, is relatively rare in patients younger than 40 years. In a large archival series, 10% of patients with Paget's disease of bone were younger than 40 years. Pain followed by pathologic fracture was the most common presenting complaint in this group of patients. There was no gender difference comparing the younger group with the older group of patients. Of the 521 patients in this series, only 10 were African-American; the others were Caucasians. Seven African-American patients were in the group of patients who were younger than 40 years. Appendicular and monostotic bone involvement was more frequent in the younger age group although these differences were not statistically significant. The incidence of malignant transformation in pagetic bone was high (30.3%), and is a reflection of the high volume of uncommon tumor referrals to our consultation service. However, there were no cases of associated malignancies in the group of patients younger than 40 years.

Published multigene classifiers suggesting outcome prediction for patients with stage UICC II colon cancer have not been translated into a clinical application so far. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable their reconstruction in routine diagnostic specimens. Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of previously published prognostic classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by "nearest shrunken centroids" with cross-validation. Previously published gene signatures were applied to our data set using "global tests" and leave-one-out cross-validation Correlation of protein expression with clinical outcome failed to separate patients with disease-free follow-up (group DF) and relapse (group R). Although gene expression profiling allowed the identification of differentially expressed genes ("DF" vs. "R"), a stable classification/prognosis signature was not discernable. Furthermore, the application of previously published gene signatures to our data was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse with established clinical and pathological parameters including microsatellite status (multivariate analysis). Our protein and gene expression analyses do not support application of molecular classifiers for prediction of clinical outcome in current routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.