Prostate cancer aggressiveness and age: Impact of p53, BCL-2 and microvessel density

Abstract

Older men are more likely to have advanced prostate cancer at time of their diagnosis, but whether prostate tumors are inherently (biologically) more aggressive with advancing age is uncertain. To address this gap in knowledge, we analyzed data from veterans (n=971) diagnosed with prostate cancer during 1991–1995. Factors included age, detection of prostate cancer by screening, prostate-specific antigen (PSA) level, anatomic stage, and Gleason score. Information on molecular markers obtained from immunohistochemical staining of prostate tissue, included B cell lymphoma-2 (bcl-2), p53, and microvessel density (MVD), each having a previously documented association with disease progression and increased risk of prostate cancer death. We first examined the bivariate association of demographic, clinical, and molecular factors with age, and found evidence that race, screening status, Gleason score, PSA, bcl-2, p53, and MVD varied across categories of age in this study population. After further characterizing the association between age and Gleason score, we used logistic regression to examine the association between age and molecular markers—accounting for race, screening status, PSA, and Gleason score. Comparing men older than 80 years to those younger than 70 years, adjusted ORs and 95% CIs were 1.89 (0.73 to 4.92), 1.91 (1.05 to 3.46), and 2.00 (1.06 to 3.78), for positive bcl-2, p53, and MVD markers, respectively; no statistically significant associations were found for men 70–79 years old, compared with men younger than 70 years. These novel findings suggest that very elderly men often present with biologically aggressive prostate cancer; the results also have potential implications for therapeutic decision-making.

Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

“…Remarkably, we also found that urine GOAT levels were directly correlated to key clinical parameters associated to PCa aggressiveness, such as Gleason score [14], age [27] and PCR [28]. Henceforth, GOAT urine levels could be also used as non-invasive biomarker for the PCa aggressiveness status.…”

Is cancer biology different in older patients?

“…Older age was consistently associated with a high-risk Decipher score, even in patients with an ISUP grade of 1, 109 reflecting the more aggressive behaviour of prostate tumours in older people. Tumours in older men also have significantly more p53 immuno reactivity (the abnormal protein produced by the mutant TP53 gene is more stable and tends to accumulate in the nucleus, which allows for detection via an immuno histochemical stain) and high micro-vessel density than younger men, 110 again suggesting that tumours are biologically more aggressive in older men. Also, the epithelial-tomesenchymal transition gene expression profile seems to differ notably between ages, 111 with older individuals having a higher downregulation of transcription factors and mesenchymal markers as well as the overexpression of adhesion factors that are associated with a more aggressive and invasive phenotype, independent of Gleason score.…”

A CD24‐p53 axis contributes to African American prostate cancer disparities

“…Age is a risk factor for being diagnosed with prostate cancer. Older men tend to be diagnosed with more advanced disease, 47 but AA men tend to be younger compared to men of other races at the time of diagnosis 48 . Also, racial disparities are greatest for low‐grade Gleason 6 disease compared with Gleason 7 to 10 disease, in which AA men are twice as likely to die of prostate cancer compared with non‐AA men 49 .…”