University of Pittsburgh Cancer Institute (UPCI)

Diagnosis and Prognosis

Early diagnosis can lead to the cure of prostate cancer. Current serum prostate specific antigen (PSA) testing has enhanced our ability to diagnose prostate cancer at early stages. Since PSA is not tumor-specific, and is also expressed abundantly by normal prostatic glandular epithelial cells, the PSA test leads to over diagnosis in some cases while missing some prostate cancers that express low levels of PSA. Thus, there is a need for new diagnostic markers that are more specific for prostate cancer. Additionally, prostate cancer is highly heterogeneous, which presents a major challenge for determining whether a patient will have rapid disease progression. Aggressive treatment of prostate cancer is often associated with side effects, but delaying the treatment of rapidly progressing prostate cancer can significantly compromise the outcome of the therapy. Thus, biomarkers for accurate prognosis are highly desirable. Several PCP investigators are trying to discover new biomarkers to improve prostate cancer diagnosis and prognosis, particularly using gene expression profiling and epigenetics studies.

Selected Publications

• Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3 is overexpressed in primary and metastatic prostatic adenocarcinomas compared to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, or normal tissue adjacent to prostatic adenocarcinoma (Bartholow TL, et. al., Diagn Pathol. 6:12-17, 2011).
• Expression of the Protein 4.1 superfamily member radixin is significantly higher in normal donor prostates, benign prostatic hyperplasia, and high-grade prostatic intraepithelial neoplasia compared to primary and metastatic prostatic adenocarcinomas (Bartholow TL, et. al., BMC Clin Pathol. 11:1-8, 2011).
• The ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis. EBP50 expression is suppressed in primary and metastatic prostatic adenocarcinoma, compared to normal donor prostate, benign prostatic hyperplasia, high grade prostatic intraepithelial neoplasia, and normal tissue adjacent to prostatic adenocarcinoma. However, expression in primary prostatic adenocarcinoma is significantly higher than metastatic prostatic adenocarcinoma (Bartholow TL, et. al., BMC Urol. 11:12-19, 2011).
• Folic acid supplementation is associated with an increased incidence of prostate cancer, and men with higher serum folate concentrations have increased cancer cell proliferation. Unexpectedly, more than 25% of patients had serum folate levels greater than six-fold adequate. Nearly half of these men reported no supplement use, suggesting either altered folate metabolism and/or sustained consumption of folic acid from fortified foods (Tomaszewski JJ, et. al., Prostate. 71:1287-93, 2011).

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