Prostate specific antigen complexed to α‐1‐antichymotrypsin in patients with intermediate prostate specific antigen levels

Abstract

BACKGROUNDThe authors attempted to evaluate prospectively the usefulness of serum prostate specific antigen (PSA) complexed to α‐1‐antichymotrypsin (PSA‐ACT) in the early detection of prostate carcinoma and its ability to discriminate between prostate carcinoma and benign prostatic hyperplasia (BPH), especially among patients with intermediate PSA levels.METHODSBetween December 1999 and August 2000, systematic sextant biopsies were performed on 281 prospective patients with prostate carcinoma who had serum PSA levels between 4.1 ng/mL and 20.0 ng/mL. The serum samples were assayed by using kits that were designed specifically for measuring serum PSA, PSA‐ACT, and free PSA levels. The clinical values of PSA, PSA‐ACT, the free PSA to total PSA ratio (F/T ratio), the free PSA to PSA‐ACT ratio, PSA density (PSAD), and PSA‐ACT density (ACTD) were compared by using receiver operating characteristic (ROC) curve analysis.RESULTSBiopsy yielded no evidence of malignancy in 198 patients, and prostate carcinoma was confirmed in 83 patients. ROC analysis demonstrated that the area under the curve (AUC) for PSA‐ACT was greater than that for total PSA and was equivalent to that for the F/T ratio in both groups of patients (PSA ranges of 4.1–20.0 ng/mL and 4.1–10.0 ng/mL, respectively). The AUC for the ACTD was greater than the AUC for the PSAD and had the highest value of all parameters.CONCLUSIONSThe measurement of PSA‐ACT represents an alternative to the use of total and free PSA. The ACTD value is the most useful for discriminating between BPH and prostate carcinoma. Cancer 2002;94:1685–91. © 2002 American Cancer Society.DOI 10.1002/cncr.10377

Comparison of the Clinical Value of Complexed PSA and Total PSA in the Discrimination between Benign Prostatic Hyperplasia and Prostate Cancer

“…Therefore, we choose such patients for comparison with candidates for radical prostatectomy to evaluate the usefulness of the complexed PSA assay. Compared with multiple studies involving patients with positive and negative prostate biopsies [2,4,5,[8][9][10][11][12][13][14][15] , in our study, the AUCs were higher for all PSA derivatives (indicating a better discrimination between benign and malignant prostatic conditions by the determination of PSA-related laboratory values). A selection effect might be a possible explanation for this phenomenon.…”

“…Some authors report rather arbitrary cut-off values for complexed and total PSA (for instance 2.9 ng/ml for complexed PSA and 3.9 ng/ml for total PSA representing the 93rd sensitivity percentile [3] or 2.9 for complexed PSA and 4.0 ng/ml for total PSA representing the 90th sensitivity percentile in their studies [12] ) or a broad range of possible cut-off values for complexed PSA [2] . Other authors used the 95th sensitivity percentile to defi ne cut-off values and obtained differing results [8,9] . We considered two pairs of cut-off values suitable for clinical application, the 95% sensitivity threshold (in this study 2.0 ng/ml for complexed and 2.5 ng/ml for total PSA) and 3.0 ng/ml for complexed PSA and 4.0 for total PSA in agreement with values suggested by others [3,12] and with the most commonly used total PSA threshold of 4.0 ng/ml.…”

Urinary CD14 as a potential biomarker for benign prostatic hyperplasia – discovery by combining MALDI‐TOF‐based biostatistics and ESI‐MS/MS‐based stable‐isotope labeling

“…Serum PSA is a well‐known tumor marker for prostate cancer, but has low specificity in differentiation of prostate cancer form BPH 24, 25. It has been reported that the serum of prostate cancer patients contains a large proportion of PSA complexed with enzyme inhibitors 26, 27, including ACT and α‐1‐antitrypsin; these two proteins are also in our list of potential marker candidates for BPH (Table 1). Moreover, it has been reported that the AUC value for PSA‐ACT complex is higher than that for total serum PSA, and equivalent to that of free/total serum PSA in cancer patients 27.…”

“…It has been reported that the serum of prostate cancer patients contains a large proportion of PSA complexed with enzyme inhibitors 26, 27, including ACT and α‐1‐antitrypsin; these two proteins are also in our list of potential marker candidates for BPH (Table 1). Moreover, it has been reported that the AUC value for PSA‐ACT complex is higher than that for total serum PSA, and equivalent to that of free/total serum PSA in cancer patients 27. It is worthy noting that in contrast to the high level of PSA in the blood of cancer patients, our results indicate that the level of PSA in the urine of cancer patients as well as normal subjects is significantly lower than that of BPH patients.…”

PSA y hK2 en el diagnóstico de cáncer de próstata

“…Okegawa et al 42 tan sólo pudieron demostrar diferencias significativas cuando se comparaba el PSA total con el cociente PSA:α 1 ACT/PSA total. Sin embargo, Saika et al 43 sí que encontraron diferencias significativas y para una sensibilidad del 90% obtuvieron especificidades del 10,8% para PSA total y 31,7% para el PSA:α 1 ACT Las investigaciones realizadas por nuestro grupo, a diferencia de otros autores 44 , revelan que el porcentaje de PSA formando complejo con α 1 ACT es más eficaz que el porcentaje de PSA libre para diferenciar la HBP y el CaP en el rango de PSA total entre 2 y 10 ng/ml y que su uso es preferible al uso del porcentaje de PSA libre [45][46][47] . Además, el porcentaje de PSA acomplejado mostró mayor discriminación entre CaP e HBP que el de PSA libre en los rangos de PSA entre 2 y 4 ng/ml 48 y entre 10 y 30 ng/ml de PSA total 49 .…”