RNA‐based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP‐2 upregulation for a subsequent prostate cancer diagnosis

Abstract

Background Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC‐related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP‐diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC‐related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2‐ERG, T2E) fusion, alpha‐methylacyl‐CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)‐2 and 9. Methods PC‐related RNAs were evaluated using a real‐time quantitative reverse transcription polymerase chain reaction (RT‐qPCR) system in pathologically ASAP‐diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4‐10 ng/mL. Results We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP‐2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP‐2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow‐up period (P = 0.003). Conclusions Although, more clinical validations are needed for the stratification of PC risk in ASAP‐diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP‐2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP‐diagnosed patients with a PSA level of 4‐10 ng/mL.

The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review

“…Many studies similarly showed an increased expression of MMP-2 in PrCa [49,53,59,61,62,91,150,153,156]. This also generally correlated with more advanced PrCa [32,75,84,92,94,119,132,133,141,146], including metastatic disease [54,69], as well as increased risk [47] and decreased survival [35,52,136]. In contrast, other publications showed no association [67,79,97] or a negative association [52,82,83,112,115].…”

“…Multiple publications have identified an increased expression in PrCa [59,61,78,83,109,113,129,153,156], including positive associations with more advanced PrCa [67,75,84,103] [92,102] and poorer prognosis [35,77,89]. Others show no association [24,47,48,52,118], and a small number show negative associations [25,31,40] with PrCa progression, indicating that MMP-9 is not universally important. However, functional studies serve to confirm its significant role, particularly in PrCa spreading, with MMP-9 ablation repeatedly shown to decrease its invasion and/or migration [57,87,100,148].…”

Multiplexed Opto-Microfluidic Biosensing: Advanced Platform for Prostate Cancer Detection

“…Recent literature and medical investigations − have identified valuable complementary targets in the detection of PCa, such as anti-α-methylacyl-CoA racemase (anti-AMACR) and matrix metalloproteinase-2 (MMP-2) . AMACR exhibits high expression in PCa epithelial cells and elicits a strong humoral response.…”

Cell renewal index in the differential diagnosis of atypical small acinar proliferation and adenocarcinoma of the prostate

“…Следует отметить, что чёткие дифференциально-диагностические критерии для АМАП и аденокарциномы на основании параметров клеточного обновления направленно разработаны не были [12]. Поиск возможностей оптимизации диагностического алгоритма при карциноме простаты и путей объективизации информации о процессах клеточного обновления диктует необходимость комплексного определения параметров процессов, задействованных в поддержании клеточного гомеостаза, в их взаимосвязи [12,13,14]. С этой целью для более объективного изучения пролиферации и апоптоза в эпителиальных клетках гормонально зависимых желёз предлагается активное использование индекса обновления клеток (ИОК) [15].…”