¹Tissue Proteomics Unit, Division of Therapeutic Proteins, CBER, Food and Drug Administration, Bethesda, Maryland, MD 20892, USA

²Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA

³Georgetown University, Department of Chemistry, Washington, District of Columbia, DC 20057, USA

⁴Cancer Genome Anatomy Project, Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland MD 20892, USA

⁵Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA

⁶Cancer Prevention Studies Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA

Correspondence to: L A Liotta, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA

Protein arrays are described for screening of molecular markers and pathway targets in patient matched human tissue during disease progression. In contrast to previous protein arrays that immobilize the probe, our reverse phase protein array immobilizes the whole repertoire of patient proteins that represent the state of individual tissue cell populations undergoing disease transitions. A high degree of sensitivity, precision and linearity was achieved, making it possible to quantify the phosphorylated status of signal proteins in human tissue cell subpopulations. Using this novel protein microarray we have longitudinally analysed the state of pro-survival checkpoint proteins at the microscopic transition stage from patient matched histologically normal prostate epithelium to prostate intraepithelial neoplasia (PIN) and then to invasive prostate cancer. Cancer progression was associated with increased phosphorylation of Akt (P<0.04), suppression of apoptosis pathways (P<0.03), as well as decreased phosphorylation of ERK (P<0.01). At the transition from histologically normal epithelium to PIN we observed a statistically significant surge in phosphorylated Akt (P<0.03) and a concomitant suppression of downstream apoptosis pathways which proceeds the transition into invasive carcinoma. Oncogene (2001) 20, 1981-1989.

laser capture microdissection; protein microarrays; apoptosis; Akt; mitogen activated protein kinase; tumor progression