peptide-phi and Prostatic-Neoplasms

Prostate-specific antigen (PSA) has revolutionized the management of prostate cancer (PCa) within the last 3 decades. This widely used tumour marker strongly correlates with the risk of harbouring a PCa but it lacks specificity. Therefore there is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. Of all PSA-based markers, only the FDA-approved prostate health index phi shows improved specificity over percent free (%fPSA) and total PSA. Other serum kallikreins or sarcosine in serum or urine show more ambiguous data. In urine, the FDA-approved prostate cancer gene 3 (PCA3) has also proven its utility in the detection and management of early PCa with advantages as compared with PSA and %fPSA. However, some aspects of its correlation with aggressiveness and the low sensitivity at very high values have to be re-examined. The detection of alterations of the androgen regulated TMPRSS2 and ETS transcription factor genes in tissue of ~50% of all PCa patients was a milestone in PCa research. But only the combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 (both use the same platform) show the expected improved accuracy for PCa detection. Comparisons of phi and PCA3, the best available PCa biomarkers so far, show an equal performance of both parameters.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Cytoskeletal Proteins; Humans; Male; Peptide PHI; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity; Serine Endopeptidases

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Topics: Aged; Antigens, Neoplasm; Area Under Curve; Biomarkers; Humans; Logistic Models; Male; Middle Aged; Neoplasm Staging; Peptide PHI; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Serine Endopeptidases

Neuropeptidergic innervation of the human testis and epididymis was investigated by immunohistochemical methods. The innervation of the epididymis was more dense than that of testis. In the testis only tyrosine hydroxylase- and neuropeptide Y-positive nerves could be found between seminiferous tubules and around blood vessels. In the connective tissue capsule of the testis also small calcitonin gene-related peptide- and metenkephalin-containing nerve fibres were seen. The epididymis was densely innervated by nerve fibres immunoreactive to tyrosine hydroxylase, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide, galanin, peptide histidine isoleusine and substance P.

Topics: Aged; Calcitonin Gene-Related Peptide; Connective Tissue; Enkephalin, Methionine; Epididymis; Galanin; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Fibers; Neuropeptide Y; Neuropeptides; Peptide PHI; Peptides; Prostatic Neoplasms; Seminiferous Tubules; Substance P; Testis; Tissue Fixation; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide