Photopheresis for Chronic Rejection of Lung Allografts

Abstract

Sensitive assays can detect angiogenic cytokines such as basic fibroblast growth factor and vascular endothelial-cell growth factor, which correlate with angiogenic activity and decreased survival.3 The intensity of angiogenesis (as indicated by the histologic microvessel count in the tumor-biopsy specimen) is a prognostic marker for a variety of solid tumors, including tumors of the colon, lung, brain, breast, and prostate, and for some nonsolid tumors, such as multiple myeloma. Many of the mutated variants of p53 are unusually resistant to intracellular biodegradation and thus accumulate in many times higher concentrations than does the wild-type analogue, and sustained high p53 concentrations connote the wild-type p53 gene mutation quite reliably. Because of their findings, Esrig et al. recommend adjuvant therapy, including chemotherapy and radiotherapy, for patients found to have extraordinarily high concentrations of (mutant) p53 in resected bladder tissue. [...]although the extent of nuclear reactivity in tumor cells was divided into four categories (0, 1 to 9, 10 to 49, and 50 to 100 percent positive nuclei), the patients were divided into two groups (those with less than 10 percent positive tumor-cell nuclei and those with 10 percent or more) on the basis of our previous study demonstrating the association between nuclear accumulation of p53 and mutations in the gene.4 Thus, the basis for the classification of the patients was whether or not there was a detectable abnormality in the results of the p53 immunohistochemical test. Bladder tumors with p53 alterations may be less responsive to adjuvant therapies (although this has not been demonstrated in vivo), but our results clearly indicate a high rate of progression despite radical surgery, even when the tumors are pathologically confined to the bladder. [...]our recommendation was based on the fact that for many patients with bladder cancer and p53 alterations, adjuvant therapy may be the best remaining option.