Azienda Ospedaliera Universitaria Integrata Verona Dipartimento AD Attività Integrata DI Chirurgia ED Oncologia - Pancreas CenterUnità Complessa DI Urologia D.O., Sede di Borgo Trento - P.le A. Stefani, 1-37121 Verona, Italy.
To evaluate Luteinizing hormone (LH) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population.
Age, percentages of positive cores at Trans Rectal Ultrasound Scan Biopsy (TRUSB) (P+), biopsy Gleason score (bGS), LH, Total Testosterone (TT), Free Testosterone (FT) and Prostate Specific Antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement treatment. Correlation analysis was performed for the patient population. Correlation analysis, linear regression and analysis of variance was computed in groups and subgroups of the prostate cancer population.
Correlation analysis of the patient population showed that LH was significantly correlated to age (p=0.02) and FT (p=0.01). The population was clustered in LH I (LH≤ 7.5 IU/l) and LH II (LH>7.5 IU/l). Correlation analysis showed significant LH correlations for TT (p< 0.0001) and FT (p=0.0004) for LH I; significant LH correlation to FT (p=0.0001) for LH II. Simple linear regression showed that LH was significantly predicted by both TT (p-Value< 0.0001) and FT (p-Value=0.0004) in LH I; but only FT (p-Value< 0.0001) in LH II. Multiple linear regression showed that LH was significantly predicted by both TT (p-Value=0.0004) and PSA (p-Value=0.03) in LH I; but only by FT (p-Value=0.003) in LH II. Analysis of variance showed that: a) LH and age were significantly lower in LH I than II; b) LH I expressed higher mean FT levels (p=0.08) and lower mean P+ (p=0.07) than LH II. The LH versus PSA plot was computed for LH group I and 3 sub clusters were created: LH I group A (LH/PSA≤ 0.25), B (0.25< LH/PSA ≤ 0.75), and C (LH/PSA>0.75). Correlation analysis showed that LH was significantly correlated to age (p=0.01), TT (p=0.03) and PSA (p=0.0004) in LH IA; LH was significantly correlated to PSA (p< 0.0001) in LH IB; and LH significantly correlated to TT (p=0.005), FT (p=0.01), and PSA (p=0.008) in LH 1C. Multiple linear regression showed that LH was significantly correlated to age (p=0.02) and PSA (p=0.01) in LH IA, to TT (p=0.01) and PSA (p< 0.0001) in LH IB, and to PSA (p=0.003) and weakly to TT (p=0.09) in LH IC. The groups differed significantly for mean levels of LH (p=0.0004), TT (p=0.005), FT (p=0.01), PSA (p< 0.0001), bGS (p=0.003). Analysis of variance between the subgroups of the patient population (LH IA, LH IB, LH IC, LH II) showed significant differences in mean levels for LH (p< 0.0001), age (p=0.004), TT (p=0.009), FT (p=0.02), PSA (p< 0.0001), PSA/FT (p< 0.0001), bGS (p=0.01), but not for P+ (p=0.10).
According to LH physiopathology, the prostate cancer population could be clustered into hypo-gonadic and non-hypo-gonadic group at diagnosis. The hypo-gonadic group expresses an aggressive tumor phenotype and might be divided into two more different significant subsets including primary and secondary hypo-gonadic patients: the former (LH II) including older patients with high LH levels, the latter (LH IA) including younger patients with low LH and LH/PSA levels (subgroup LH IA). The non-hypo-gonadic group showed a less aggressive tumor phenotype and according to the LH/PSA ratio might beclustered into LH IB (0.25< LH/PSA≤ 0.75) and LH IC (LH/PSA>0.75), the former showing a more aggressive tumor phenotype than the latter. Confirmatory studies are necessary.
Porcaro AB, Petrozziello A, Migliorini F, Caruso B, Cocco C, Sava T, Ghimenton C, Romano M, Monaco C, Comunale L. Are you the author?
Reference: Anticancer Res. 2011 Mar;31(3):1071-8.