Alinezhad Saeid, Väänänen Riina-Minna, Ochoa Natalia Tong, Vertosick Emily A, Bjartell Anders, Boström Peter J, Taimen Pekka, Pettersson Kim
Division of Biotechnology, University of Turku, Tykistökatu 6A 6th floor, 20520, Turku, Finland.
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
BMC Urol. 2016 Feb 29;16:10. doi: 10.1186/s12894-016-0128-8.
The high false negative rates for initial prostate biopsies refer a large number of the men for repeat biopsies each year. Therefore, biomarkers associated with high risk of the presence of malignancy in histologically benign biopsies could provide a tool to discriminate the patients who need repeat biopsy or intensive follow-up from those who do not. Here we examined the diagnostic applicability of alpha-methylacyl CoA racemase (AMACR) and androgen receptor (AR) mRNA expression and AMACR protein levels in benign and cancerous prostatic tissue.
AMACR and AR mRNA levels were measured with quantitative, reverse-transcription PCR (qRT-PCR) assays in 79 radical prostatectomy (RP) cases (including 69 benign (RP-Be) and 69 cancerous (RP-PCa) samples) and 19 benign prostate samples obtained from cystoprostatectomies. To further determine the detailed areas of altered AMACR expression, AMACR mRNA level measurement and protein staining were performed for three cross-sectioned RP cases.
The median AMACR and AR expression levels were 194.6 (p < 0.0001) and 6.6 (p = 0.0004) times higher in RP-PCa samples than in the benign cystoprostatectomy (CP) samples, respectively. There was no statistically significant difference between RP-PCa and RP-Be samples, except for AMACR/KLK3 (Kallikrein-Related Peptidase 3) ratio, which was significantly higher in RP-PCa samples than in RP-Be samples (p = 0.016). In the systematic study of cross-sections, AMACR mRNA was detected in all of the studied areas including histologically benign tissue, but at significantly higher levels in carcinoma areas (p < 0.001). AMACR protein expression was detected in 80 % (28/35) of the areas that contained carcinoma and in 37 % (44/119) of the benign and PIN areas from the same patients.
AMACR transcripts were detected in all RP-PCa and RP-Be samples but not in non-cancerous CP samples, which suggest a global increase of AMACR expression in cancerous prostates. Therefore patients with false negative biopsies might benefit from an AMACR mRNA measurement when assessing their cancer risk.
初次前列腺活检的高假阴性率导致每年有大量男性需要重复活检。因此，在组织学上为良性的活检中，与恶性肿瘤高风险相关的生物标志物可以提供一种工具，用于区分需要重复活检或密切随访的患者与不需要的患者。在此，我们研究了α-甲基酰基辅酶A消旋酶（AMACR）和雄激素受体（AR）mRNA表达以及AMACR蛋白水平在前列腺良性和癌性组织中的诊断适用性。
采用定量逆转录聚合酶链反应（qRT-PCR）检测了79例根治性前列腺切除术（RP）病例（包括69例良性（RP-Be）和69例癌性（RP-PCa）样本）以及19例从膀胱前列腺切除术中获得的良性前列腺样本中AMACR和AR mRNA水平。为进一步确定AMACR表达改变的详细区域，对3例RP病例的横断面进行了AMACR mRNA水平测定和蛋白染色。
RP-PCa样本中AMACR和AR的表达水平中位数分别比良性膀胱前列腺切除术（CP）样本高194.6倍（p < 0.0001）和6.6倍（p = 0.0004）。除了AMACR/KLK3（激肽释放酶相关肽酶3）比值外，RP-PCa样本和RP-Be样本之间无统计学显著差异，该比值在RP-PCa样本中显著高于RP-Be样本（p = 0.016）。在横断面的系统研究中，在所有研究区域包括组织学上为良性的组织中均检测到AMACR mRNA，但在癌区水平显著更高（p < 0.001）。在同一患者的含有癌的区域中，80%（28/35）检测到AMACR蛋白表达，在良性和前列腺上皮内瘤变区域中，37%（44/119）检测到AMACR蛋白表达。
在所有RP-PCa和RP-Be样本中均检测到AMACR转录本，但在非癌性CP样本中未检测到，这表明癌性前列腺中AMACR表达整体增加。因此，活检结果为假阴性的患者在评估癌症风险时，可能会从AMACR mRNA检测中受益。
