PAM50 classifier defines prostate cancer subtypes
medwireNews: Patients with prostate cancer can be classified into luminal- and basal-like subtypes using the well-known PAM50 algorithm, and the subtypes correlate with clinical outcome, researchers report.
In addition, the PAM50 subtype may be associated with response to postoperative androgen deprivation therapy, they say.
Felix Feng (University of California, San Francisco, USA) and team applied the PAM50 classifier, which is commonly used to identify the major molecular subtypes of breast cancer, to 1567 retrospective prostate cancer samples from patients with a median follow-up time of 10 years and to 2215 prospectively collected samples.
They found that the samples consistently segregated into luminal A, luminal B, and basal subtypes in both the retrospective (34.3%, 28.5%, and 37.1%, respectively) and prospective (33.3%, 32.6%, and 34.1%, respectively) cohorts. They note that the human epidermal growth factor receptor 2 (HER2) subtype was excluded from the analysis because HER2 is not commonly amplified in prostate cancer.
In addition, the basal lineage CD49f signature was amplified in basal-like samples, while luminal lineage markers NKX3.1, KRT18, and AR (androgen receptor) were enriched in the luminal subtypes.
Analysis of the retrospective data, obtained from six different cohorts, showed that patients with basal and luminal A tumors had significantly better 10-year distant metastasis-free survival than those with luminal B tumors, at 73% and 73% versus 53%, respectively, and hazard ratios (HRs) of 0.66 and 0.55, respectively, after adjusting for clinicopathologic variables.
Biochemical recurrence-free survival was also significantly better with basal (HR=0.81) and luminal A tumors (HR=0.79) than with luminal B tumors, while patients with luminal A tumors had significantly improved prostate cancer-specific survival (HR=0.50) and overall survival (HR=0.69) compared with those with luminal B tumors.
Despite their poor prognosis, patients with the luminal B subtype appeared to respond better to hormone therapy than those with non-luminal B subtypes in a subcohort of 315 patients matched for clinicopathologic markers, with a median 13 years of follow-up, who either did (n=105) or did not (n=210) receive treatment with androgen-deprivation therapy (ADT).
Specifically, 10-year metastasis rates were 33% with ADT and 55% without among patients with the luminal B subtype, compared with 37% and 21%, respectively, in those with non-luminal B subtypes.
Furthermore, Cox proportional hazards modelling showed a statistically significant interaction between ADT and the luminal B subtype.
Feng and team suggest that patients with luminal A tumors did not derive the same benefit from ADT as those with luminal B tumors “because these patients already have a better prognosis; thus, aggressive treatment may make little difference in the eventual outcome.”
Writing in JAMA Oncology, the researchers conclude that “[t]he luminal B subtype represents a subgroup of prostate cancers with poor prognosis combined with biological differences in AR-signaling that result in improved response to postoperative ADT.”
They add: “These findings contribute novel insight into prostate cancer biology, providing a potential clinical tool to personalize ADT treatment for prostate cancer by predicting which men may benefit from ADT after surgery.”
By Laura Cowen
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