osteoprotegerin and Carcinoma--Neuroendocrine

The incidence of prostate cancer has increased dramatically during the last 10-15 years and it is now the commonest cancer in males in developed countries. The increase is mainly caused by the increasing use of opportunistic screening or case-finding based on the use of prostate-specific antigen (PSA) testing in serum. With this approach, prostate cancer is detected 5-10 years before giving rise to symptoms and on average 17 years before causing the death of the patient. While this has led to detection of prostate cancer at a potentially curable stage, it has also led to substantial overdiagnosis, i.e. detection of cancers that would not surface clinically in the absence of screening. A major challenge is thus to identify the cases that need to be treated while avoiding diagnosing patients who will not benefit from being diagnosed and who will only suffer from the stigma of being a cancer patient. It would be useful to have prognostic markers that could predict which patients need to be diagnosed and which do not. Ideally, it should be possible to measure these markers using non-invasive techniques, i.e. by means of serum or urine tests. As it is very useful for both early diagnosis and monitoring of prostate cancer, PSA is considered the most valuable marker available for any tumor. Although the prognostic value of PSA is limited, measurement of the proportion of free PSA has improved the identification of patients with aggressive disease. Furthermore, the rate of increase in serum PSA reflects tumor growth rate and prognosis but, due to substantial physiological variation in serum PSA, reliable estimation of the rate of PSA increase requires follow-up for at least 2 years. Algorithms based on the combined use of free and total PSA and prostate volume in logistic regression and neural networks can improve the diagnostic accuracy for prostate cancer, and assays for minor subfractions of PSA and other new markers may provide additional prognostic information. Markers of neuroendocrine differentiation are useful for the monitoring of androgen-independent disease and various bone markers are useful in patients with metastatic disease.

Topics: Aged; Alkaline Phosphatase; Androgens; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Carcinoma, Neuroendocrine; Chromogranin A; Chromogranins; Collagen Type I; Disease Progression; Glycoproteins; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasm Staging; Osteoprotegerin; Peptide Fragments; Phosphopyruvate Hydratase; Prevalence; Probability; Procollagen; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Testosterone; Tissue Kallikreins

The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role.. To characterize the RANK/RANKL/OPG pathway in patients affected with NET.. Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups.. Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups.. This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.

Topics: Adult; Aged; Bone Neoplasms; Carcinoma, Neuroendocrine; Disease Progression; Early Diagnosis; Female; Gene Expression Regulation, Neoplastic; Humans; Intestinal Neoplasms; Lung Neoplasms; Male; Middle Aged; Osteoprotegerin; Pancreatic Neoplasms; Predictive Value of Tests; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; ROC Curve; Signal Transduction; Survival Analysis