Tan J S J, Ong K C, Ong D B L, Wu Y S, Razack A, Kuppusamy S, Lim J, Rhodes A
University Malaya, Faculty of Medicine, Department of Pathology, Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
Malays J Pathol. 2019 Dec;41(3):243-251.
Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene.
From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies.
Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent.
CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.
雄激素受体（AR）基因中CAG重复序列的多态性表达可能会影响AR的活性、前列腺癌的发生以及TMPRSS2-ERG融合事件。此外，这种多态性可能是前列腺癌发生和ERG癌基因表达中观察到的种族差异的原因。我们研究了马来西亚前列腺癌男性活检组织中AR和ERG的表达，并将其与这些患者AR基因中CAG重复序列的长度相关联。
通过一项PSA筛查计划，发现161名男性血液中的PSA水平升高，并接受了前列腺组织活检。从血液中提取DNA，通过PCR扩增AR基因的外显子1并进行测序。计算CAG重复序列的数量，并将其与匹配的肿瘤活检组织中ERG和AR的免疫组化表达进行比较。
PSA水平升高的男性中，89例被诊断为前列腺癌，72例为良性前列腺增生（BPH）。前列腺癌患者和BPH患者的CAG重复长度没有显著差异。CAG重复长度与年龄、PSA或肿瘤分级无关，尽管CAG重复较长与肿瘤分期相关。ERG和AR分别在36%和86%的癌症中表达。CAG重复长度与ERG或AR表达之间没有显著关联。然而，ERG和AR表达之间存在显著的负相关关系。此外，与马来或华裔男性相比，印度男性中ERG阳性肿瘤的比例显著更高。
CAG重复长度与前列腺癌或ERG或AR的表达无关。然而，ERG在马来西亚印度男性的前列腺癌中似乎比在其他马来西亚种族的前列腺癌中更常见，并且在本研究中其表达与AR表达呈负相关。
