Markers of clinical utility in the differential diagnosis and prognosis of prostate cancer

Abstract

Molecular diagnostics is a rapidly evolving area of surgical pathology, that is gradually beginning to transform our diagnostical procedures for a variety of tumors. Next to molecular prognostication that has begun to complement our histological diagnosis in breast cancer, additional testing to detect targets and to predict therapy response has become common practice in breast and lung cancer. Prostate cancer is a bit slower in this respect, as it is still largely diagnosed and classified on morphological grounds. Our diagnostic immunohistochemical armamentarium of basal cell markers and positive markers of malignancy now allows to clarify the majority of lesions, if applied to the appropriate morphological context (and step sections). Prognostic immunohistochemistry remains a problematic and erratic yet tempting research field that provides information on tumor relevance of proteins, but little hard data to integrate into our diagnostic workflow. Main reasons are various issues of standardization that hamper the reproducibility of cut-off values to delineate risk categories. Molecular testing of DNA-methylation or transcript profiling may be much better standardized and this review discusses a couple of commercially available tests: The ConfirmDX test measures DNA-methylation to estimate the likelihood of cancer detection on a repeat biopsy and may help to reduce unnecessary biopsies. The tests Prolaris, OncotypeDX Prostate, and Decipher all are transcript tests that have shown to provide prognostic data independent of clinico-pathological parameters and that may aid in therapy planning. However, further validation and more comparative studies will be needed to clarify the many open questions concerning sampling bias and tumor heterogeneity.