In patients with PTEN loss, cancer growth is driven by the PI3K-AKT pathway, which doesn't activate the PSA gene. This can lead to significant disease progression with a low or stable PSA, making PSA a poor surrogate for disease activity in this sub-population.
While Next-Gen Sequencing (NGS) can detect PTEN genetic loss, Immunohistochemistry (IHC) is often more practical for routine clinical use. IHC directly measures protein loss, requires less tissue, is faster, more affordable, and highly scalable.
Unlike androgen receptor mutations which arise under treatment pressure, PTEN loss is an earlier event. Therefore, archival tissue from a primary biopsy is generally sufficient for determining PTEN status, even years later at metastatic relapse, avoiding a new invasive procedure.
PTEN loss is seen very early in prostate cancer development. However, its primary role is not initiating the cancer but rather accelerating its progression in grade, stage, and disease state. The initial driver is more often related to androgen receptor biology.