Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we perform multi-region, targeted next generation sequencing and construct phylogenetic trees in men with prostate cancer with synchronous LN metastasis to better define the pathologic and molecular features of primary disease most likely to spread to the LNs. Collectively, we demonstrate that a combination of histopathologic and molecular factors, including tumor grade, presence of extra-prostatic extension, cellular morphology, and oncogenic genomic alterations are associated with synchronous LN metastasis.
Nature communications. 2024 May 21*** epublish ***
Udit Singhal, Srinivas Nallandhighal, Jeffrey J Tosoian, Kevin Hu, Trinh M Pham, Judith Stangl-Kremser, Chia-Jen Liu, Razeen Karim, Komal R Plouffe, Todd M Morgan, Marcin Cieslik, Roberta Lucianò, Shahrokh F Shariat, Nadia Finocchio, Lucia Dambrosio, Claudio Doglioni, Arul M Chinnaiyan, Scott A Tomlins, Alberto Briganti, Ganesh S Palapattu, Aaron M Udager, Simpa S Salami
Department of Urology, Michigan Medicine, Ann Arbor, MI, USA. ., Department of Urology, Michigan Medicine, Ann Arbor, MI, USA., Department of Urology, Vanderbilt University, Nashville, TN, USA., Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA., College of Literature, Science, and Arts, University of Michigan, Ann Arbor, MI, USA., Michigan Center for Translational Pathology, Michigan Medicine, Ann Arbor, MI, USA., Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA., Department of Pathology, Universita Vita-Salute San Raffaele, Milan, Italy., Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology, Universita Vita-Salute San Raffaele, Milan, Italy., Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA. ., Department of Urology, Michigan Medicine, Ann Arbor, MI, USA. .