Intraductal Carcinoma of Prostate (IDC-P), Grade Group, and Molecular Pathology: Recent Advances and Practical Implication

The Gleason grading system for prostatic carcinoma is widely used internationally and is based on microscopic architectural patterns of tumors. Over the years, there have been modifications to the original grading system established by Donald F Gleason in 1966 and refined in 1974 which have subsequently been established by the World Health Organization in its WHO Classification of Tumors of the Urinary System and Male Genital Organs book, published in 2016. There have been certain practical issues associated with the changes, of note, the addition of intraductal carcinoma of prostate (IDC-P), which unlike its breast counterpart rarely occurs in isolation without association with invasive carcinoma and tends to be associated with high-grade invasive carcinoma. In addition, the Grade group system has been introduced which categorizes tumors into prognostically relevant groups based on the histological grade scores. The grade group system brings to light the importance of making accurate scoring and subsequent grouping of the tumors as it affects the clinical treatment, prognostic implication and stage assignment. Molecular pathology of the prostate is not widely utilized in clinical practice, but is emerging. The most common genomic aberration in prostate cancer includes gene fusion, amplification, deletion, and mutation. In addition, up and down regulation of gene expression in critical cellular pathways is also at play. A series of long noncoding RNA expression changes have been also unveiled from transcriptome sequencing data. They play a regulatory role in prostate cancer and are promising diagnostic and potentially prognostic markers as well as molecular treatment strategy. In this review, we summarize recent advances in molecular pathology of prostate cancer and their emerging clinical utility with currently available molecular tests. In this review article, we discuss the followings: 1) Gleason grading system with its modification, 2) Grade group, 3) Intraductal carcinoma, and 4) molecular pathology. Additionally, we present that molecular studies continue to emerge, and there is significant opportunity for targeted therapeutic options that remains to be explored in depth.