Husain I, Sagar P, Shukla S, Babu S, Singhai A, Sankhwar S N, Husain N
Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh.
ONGC Hospital, Dehradun.
Kathmandu Univ Med J (KUMJ). 2018;16(64):277-280.
Background Fusions of transmembrane protease, serine 2 (TMPRSS2) with erythroblast transformation specific transcription factors have been found in prostate cancer. The v-etserythroblastosis virus E26 oncogene homologue (ERG) is a proto-oncogene of the erythroblast transformation specific transcription factor family. TMPRSS2-ERG fusion is the most common molecular alteration present in about 50% of prostatic adenocarcinomas. Androgen receptor (AR) plays a key role in prostate development and is involved in the progression of prostate cancer. Objective To evaluate the significance of combined ERG and AR expression in cases of prostatic adenocarcinoma. Method The study was conducted at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Formalin fixed-paraffin embedded archival prostatic tissue specimens were obtained. A total of 10 cases of prostatic adenocarcinoma were included in the study. Immunohistochemistry for Androgen receptor was done by the standard protocol. Multiplex immunohistochemical staining was done for ERG+CK5 using a primary antibody cocktail of mouse and rabbit antibodies. Result Specific AR immunostaining was exclusively nuclear and was present in all 10 cases in varying intensity. Specific ERG immunostaining was nuclear and was present in seven cases (70%) and absent in three cases (30%). The three cases that were negative for ERG had a Gleason score of ≤ 6 and the AR staining was strong and present in about 90% of the cells. Gleason score was directly related to the ERG staining while AR staining was inversely related to the ERG staining. Conclusion The prognostic value of combined ERG and AR over-expression, its associated genes should be further investigated as potential therapeutic targets in prostate cancer progression. Preliminary data is being presented. Larger prospective studies with survival analysis are essential for prognostic significance.
背景 在前列腺癌中发现了跨膜蛋白酶丝氨酸2(TMPRSS2)与成红细胞转化特异性转录因子的融合。v-ets成红细胞增多症病毒E26癌基因同源物(ERG)是成红细胞转化特异性转录因子家族的原癌基因。TMPRSS2-ERG融合是约50%前列腺腺癌中最常见的分子改变。雄激素受体(AR)在前列腺发育中起关键作用,并参与前列腺癌的进展。目的 评估ERG和AR联合表达在前列腺腺癌病例中的意义。方法 该研究在印度北方邦勒克瑙的拉姆·马诺哈尔·洛希亚医学科学研究所进行。获取福尔马林固定石蜡包埋的前列腺组织存档标本。本研究共纳入10例前列腺腺癌病例。采用标准方案进行雄激素受体免疫组织化学检测。使用小鼠和兔抗体的一抗混合物对ERG+CK5进行多重免疫组织化学染色。结果 特异性AR免疫染色仅见于细胞核,在所有10例病例中均有不同强度的表达。特异性ERG免疫染色见于细胞核,7例(70%)呈阳性,3例(30%)呈阴性。ERG阴性的3例病例Gleason评分≤6,AR染色强,约90%的细胞呈阳性。Gleason评分与ERG染色直接相关,而AR染色与ERG染色呈负相关。结论 ERG和AR联合过表达的预后价值及其相关基因应作为前列腺癌进展的潜在治疗靶点进一步研究。现将初步数据呈现。进行生存分析的更大规模前瞻性研究对于判断预后意义至关重要。