Re: Tracking the clonal origin of lethal prostate cancer

摘要

Editorial Comment: The clinical relevance of heterogeneity of cancer within the prostate is a hotly debated topic. Prostate cancer, perhaps more than other solid urological malignancies, carries wide morphological and genetic heterogeneity within the prostate. It has been previously suggested that metastatic disease in the patient with prostate cancer, while highly heterogeneous in and of itself, arises from a single cell population in the prostate. In other words while individual metastases take on new genetic mutations that may make the cells more aggressive, their genetic signature can be traced back to 1 cell population in the prostate. This observation has served as the basis for the assertion that destruction of the most aggressive clonal population in the prostate may remove its lethal potential. This concept, often called index lesion control or ablation, relies on detection of the appropriate index lesion. This case study of 1 individual suggests that metastases can be derived from a low grade focus in the prostate, even in the presence of higher grade regions of tumor elsewhere. This finding, if true, brings about some confusion not only in focal therapy, but also in risk stratification in patients with prostate cancer in general. Furthermore, the recent reports of gene panels capable of more accurately predicting risk than histological findings alone are drawn into question. If the genetic basis for metastatic progression is not found in all tumors within the gland, then how can random sampling of the gland allow accurate risk assessment?