EVALUATION OF BIOMARKERS IN BREAST AND PROSTATE-CANCER

p53, p185(erbB-2), and epidermal growth factor (EGF) receptor are well -characterized biomarkers in invasive adenocarcinoma of the breast and in ductal carcinoma in situ. erbB-2 Protein (p185(erbB-2)) must be id entified clearly on cytoplasmic membranes while cytoplasmic expression is ignored for breast cancers to be classified as overexpressing p185 (erbB-2). For p53, nuclear staining and the percent positive cells are considered, but rules for ''cut-offs'' are not defined. Evaluation cr iteria for biomarkers in prostate cancer are preliminary and the ''rul es'' may not be the same as for breast cancer. Because the initial met hods of fixation and tissue processing can change both the pattern and intensity of immunohistochemical identification of specific antigens and localization of receptors may change after the receptor-ligand int eractions, we evaluated the effects of fixation both on the immunoloca lization and intensity of expression of p53, p185(erbB-2), and EGF rec eptor. We also studied the patterns of p185(erbB-2), and p53 expressio n in a series of breast cancers evaluated concomitantly with a group o f prostate cancers. Our results confirm that p53 mutations are common in breast cancer and that there is strong expression of p185(erbB-2) o n the membranes of a subset of breast cancers. The patterns of stainin g for both p53 and p185(erbB-2), different in prostate and breast canc ers. A much lower proportion of prostate tumors than breast tumors hav e more than 10% of tumor cells with detectable nuclear p53 protein, bu t this proportion increases markedly in metastatic tumors or in primar y stage D prostate cancer. In addition, a higher concentration of prim ary antibody is necessary to demonstrate nuclei showing p53 accumulati on in prostate cancers than in breast cancers. The expression of p185( erbB-2) in prostate cancer is much coarser and more punctate than that observed in breast cancer; extensive cytoplasmic staining usually is detected in most prostatic adenocarcinomas. Concentrations of primary antibody to p185(erbB-2) that will stain membranes of breast cancers w ill not stain prostate cancer cells as strongly. However, the expressi on of p53 and/or p185(erbB-2) should not be ignored in prostate cancer since the rules for correlation of these biomarkers with the clinical outcome, or for use as surrogate endpoint biomarkers, have not been d eveloped. Neutral buffered formalin is a poor initial fixative compare d with other fixatives for demonstrating p53 accumulation or p185(erbB -2) expression. The effect of formalin fixation can be reversed with a ntigen retrieval methods, increasing detection markedly in cells with p53 accumulation. (C) 1994 Wiley-Liss, Inc.