Застосування % вПСА та % [-2]проПСА як можливих біомаркерів при диференційній діагностиці пухлин передміхурової залози

Abstract

Проведено вивчення прогностичних властивостей % вільного простатоспецифічного антигену (% вПСА) та % [-2]проПСА для використання їх при проведенні диференційної діагностики раку передміхурової залози (РПЗ) серед 246 пацієнтів різного віку (49-79 років) без будь-яких ознак урогенітальних інфекцій. Проведені дослідження встановили наявність більш високого прогностичного потенціалу у % [-2] проПСА порівняно з % вПСА в діапазоні загального ПСА (зПСА) в крові пацієнтів в межах 2,1 – 20,0 нг/мл. Крім того, % [-2]проПСА, на відміну від % вПСА, був придатним не тільки для визначення РПЗ, а також виявив ефективність для дискримінації агресивних злоякісних пухлин від індолентних пухлин, оскільки абсолютна величина % [-2]проПСА прямим чином залежала від величини рахунку Глісона; Изучено прогностические свойства % свободного ПСА (% сПСА) и % [-2]проПСА для использования в дифференциальной диагностике различных патологических состояний предстательной железы (ПЖ), а именно рак ПЖ (РПЖ) агрессивного и неагрессивного генеза, а также доброкачественной гиперплазии ПЖ. Исследования были проведены среди 246 пациентов в возрасте 49-79 лет, которые характеризовались отсутствием каких-либо признаков урогенитальных инфекций. Проведенные исследования установили наличие более высокого прогностического потенциала у % [-2]проПСА в сравнении с % сПСА в диапазоне концентраций общего ПСА (оПСА) в крови пациентов в пределах 2,1 – 20 нг/мл. Кроме этого, % [-2]проПСА, в отличии от % сПСА, оказался эффективным не только при определении РПЖ, а также обладал дискриминационными возможностями для выявления агрессивных злокачественных опухолей ПЖ, поскольку абсолютная величина % [-2]проПСА прямым образом зависела от значения счета Глисона; Prostate specific antigen (PSA) is a serum marker that is widely used as an aid in the detection of prostate cancer. However, since many prostate cancers progress slowly, there is also an urgent need for better markers to identify prostatic tumors of high malignancy. Poorly differentiated prostate cancers and those that have the potential to spread beyond the prostatic capsule are of particular concern. [-2]proPSA is a constituent of the free PSA (fPSA) which is secreted mainly by prostatic epithelial tissue after malignant transformation. In view of this its specificity for cancer emerging is anticipated. Admittedly, fPSA exists in uncomplexed state without protease inhibitors. It is secreted by epithelial prostate cells of both peripheral and central zone. A research was devoted to studying prognostic patterns of % [-2]proPSA for the discrimination of benign and malignant tumors of prostate in human males in the age interval of 49-79 years. [-2]proPSA was identified in the blood sera of 246 patients by the aid of immunochemical analyzer Chem Well (USA) using ELISA kits of DL Develop with double antibodies against the analyte. Tumor aggressiveness was classified by Gleason grading of biopsies. Then % [-2]proPSA was calculated according to the formula: % [-2]proPSA = [-2]proPSA / fPSA × 100%. fPSA and tPSA were also identified immunochemically. % fPSA was estimated as following: % fPSA = fPSA / tPSA × 100%. Statistical evaluation of raw data was done by the non-parametric methods of Mann-Whitney and Kruskal-Wallis. The determination of % [-2]proPSA and % fPSA in three groups of patients with malignant tumors of prostate (PCa) (107 patients), with benign hyperplasia of prostate (BPH) (71 patients) and without any evidence of prostate pathology (EPP) – 68 persons was executed. The statistically meaningful differences in % [-2]proPSA contents were elucidated between all three groups of patients for the wide range of total prostate specific antigen (tPSA) concentrations (0-20 ng/ml). Incidentally mean value of % [-2]proPSA was shown to be dependent of tPSA concentration and prostate pathology. Thus, in EPP group blood contents of [-2]proPSA equaled 5 pg/ml, BPH – 9 pg/ml and PCa – 10,5 pg/ml in 0–2 ng/ml tPSA range whereas the elevation of tPSA in the blood simultaneously increased [-2]proPSA mean values for all three groups of patients. In this connection, for tPSA range 4–10 ng/ml [-2]proPSA mean achieved 14 pg/ml, 21 pg/ml and 23,5 pg/ml in EPP, BPH and PCa patients, respectively. In the last diapason of tPSA (10,1–20,0 ng/ml) [-2]proPSA mean was 28 pg/ml for BPH and 43 pg/ml for PCa. Furthermore, analysis of discriminative qualities of % [-2]proPSA as to the differential diagnostics between malignant and nonmalignant states revealed a high prognostic potential for prostate tumor risk assessment. Apart from this, % [-2] proPSA of PCa patients was shown to correlate highly with Gleason score. In PCA patients having malignancies with Gleason score ≥7 [-2]proPSA mean values significantly surpassed this index in PCa patients with indolent tumors (Gleason score 6 or less). Moreover, in the Gleason score span 5-7% [-2]proPSA linearly increased and then reached its maximum at Gleason score 9. Thus, % [-2]proPSA may be proposed for further application in medical practice as independent biomarker or in conjunction with PSA test for strengthening its specificity, the latter being warranted by the peculiarities of [-2]proPSA, a stable component of free PSA (fPSA), which is directly related to malignant transformation of prostate. Further investigations will be dealt with the evaluation of prognostic qualities of other [-2]proPSA derivative, namely prostate health index, which is a product of ratio [-2]proPSA to fPSA and √tPSA. The prognostic characteristics of aforementioned indices will be compared and assessed.