宫颈腺癌患者细胞质-细胞核AR表达比率的预后意义-东南大学学报医学版

宫颈腺癌患者细胞质-细胞核AR表达比率的预后意义

单位：南京大学医学院附属鼓楼医院妇产科, 江苏南京 210008

分类号：R737.33

出版年·卷·期（页码）：2024·43·第三期（329-336）

摘要：

目的:利用免疫组化探究雄激素受体(AR)在宫颈腺癌中的表达模式及其与预后的关系。方法:对30例因子宫腺肌症等良性疾病而接受全子宫切除术患者的正常宫颈组织标本,和86例因宫颈腺癌而接受全子宫切除术患者的肿瘤组织标本进行AR 免疫组化染色,收集研究对象的一般资料,根据 AR 表达情况评估各临床病理特征与患者临床结局之间的关系。结果:83%(25/30)的正常宫颈组织显示AR在细胞核阳性表达,细胞质不表达,而与正常宫颈组织相比,AR在宫颈腺癌组织则呈现出不同的表达模式,94%(81/86)的患者有AR染色,其中82%(66/81)显示出核-质双染色,12%(10/81)显示出明显的单一胞质阳性,只有6%(5/81)的患者显示出与正常宫颈组织相似的单一核染色。且在核-质双染色的患者中,细胞质表达更为明显。为了更为准确地描述AR在肿瘤细胞不同亚细胞定位的表达情况,我们采用细胞质/细胞核比率对其表达进行量化。比率＞2.5组更易发生淋巴结转移(P＜0.01)和肌层浸润(P＜0.01),且波形蛋白(vimentin) 阳性率较高(P＜0.01)。Kaplan-Meier 分析显示,细胞质与细胞核 AR 表达比率越高,生存率越低。单变量和多变量Cox回归分析表明,AR胞质/胞核表达比率是远处转移的独立预后因素。结论:AR的细胞质与细胞核表达比率是一个独立的预后因素,有望成为宫颈腺癌患者远处转移风险的预测指标。

Objective: To investigate the expression pattern of androgen receptor(AR) in cervical adenocarcinoma and the relationship between AR expression and prognosis using immunohistochemistry. Methods: Immunohistochemical staining for AR was performed on normal cervical tissue specimens from 30 patients who underwent total hysterectomy for benign diseases such as adenomyosis and 86 tumor tissue specimens from patients who underwent total hysterectomy for cervical adenocarcinoma. General information of the subjects was collected.The relationship between each clinicopathological feature and patient survival was assessed on the basis of AR expression. Results: 83%(25/30) of normal cervical tissues showed positive nuclear staining, whereas compared to normal cervical tissues, cervical adenocarcinoma tumor tissues showed different modes of expression of AR, with 94%(81/86) of patients AR positive, of which 82%(66/81) showed nuclear-plasmic double staining, 12%(10/81) showed a clear single cytoplasmic positivity, and only 6%(5/81) showed AR nuclear staining similar to normal cervical tissue. In patients with nuclear-plasmic double staining, cytoplasmic staining was more noticeable in AR. We measured the expression of AR utilizing the cytoplasmic-cytonuclear ratio in order to more precisely characterize its expression in various subcellular localizations of tumor cells. The ratio>2.5 group had more patients with positive lymph nodes(P＜0.01) and deep myometrial invasion(P＜0.01) compared to the ratio≤2.5 group. Additionally, the ratio>2.5 group had a higher incidence of vimentin positivity(P＜0.01). Kaplan-Meier analyses revealed a higher cytoplasmic-to-cytonuclear ratio of AR expression associated with lower survival rates. Univariate and multivariate Cox regression analyses identified it as an independent prognostic factor for distant metastasis. Conclusion: The cytoplasmic-to-cytonuclear ratio of AR expression is an independent prognostic factor, offering potential as a predictor for the risk of distant metastasis in cervical adenocarcinoma patients.

参考文献：

[1] SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[2] WELCH H G,KRAMER B S,BLACK W C.Epidemiologic signatures in cancer[J].N Engl J Med,2019,381(14):1378-1386.
[3] MENG Y,CHU T,LIN S,et al.Clinicopathological characteristics and prognosis of cervical cancer with different histological types:a population-based cohort study[J].Gynecol Oncol,2021,163(3):545-551.
[4] 封旭,蔡云朗,沈杨.雌激素受体亚型对妇科疾病影响的研究进展[J].东南大学学报(医学版),2013,32(5):651-654.
[5] GELMANN E P.Molecular biology of the androgen receptor[J].J Clin Oncol,2002,20(13):3001-3015.
[6] QIU M,BAO W,WANG J,et al.FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer[J].BMC Cancer,2014,14:78.
[7] TRABERT B,MICHELS K A,ANDERSON G L,et al.Circulating androgens and postmenopausal ovarian cancer risk in the Women's Health Initiative Observational Study[J].Int J Cancer,2019,145(8):2051-2060.
[8] COLLETTE F,HAMOIR M,VAN EECKHOUT P,et al.Metastatic cutaneous apocrine adenocarcinoma successfully treated with systemic anti-androgen therapy-a case report[J].Clin Case Rep,2020,8(12):3472-3478.
[9] VISCUSE P V,PRICE K A,GARCIA J J,et al.First line androgen deprivation therapy vs.chemotherapy for patients with androgen receptor positive recurrent or metastatic salivary gland carcinoma-a retrospective study[J].Front Oncol,2019,9:701.
[10] YANG H Y,WU C H,TSAI C C,et al.Primary ductal adenocarcinoma of lacrimal gland:two case reports and review of the literature[J].Taiwan J Ophthalmol,2018,8(1):42-48.
[11] LEE S H,YANG Y J,KIM K M,et al.Altered urinary profiles of polyamines and endogenous steroids in patients with benign cervical disease and cervical cancer[J].Cancer Lett,2003,201(2):121-131.
[12] NAIR H B,LUTHRA R,KIRMA N,et al.Induction of aromatase expression in cervical carcinomas:effects of endogenous estrogen on cervical cancer cell proliferation[J].Cancer Res,2005,65(23):11164-11173.
[13] SCHOLL S,POPOVIC M,DE LA ROCHEFORDIERE A,et al.Clinical and genetic landscape of treatment naive cervical cancer:alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome[J].EBioMedicine,2019,43:253-260.
[14] NOEL J C,BUCELLA D,FAYT I,et al.Androgen receptor expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix[J].Int J Gynecol Pathol,2008,27(3):437-441.
[15] SUH-BURGMANN E,SIVRET J,DUSKA L R,et al.Long-term administration of intravaginal dehydroepiandrosterone on regression of low-grade cervical dysplasia-a pilot study[J].Gynecol Obstet Invest,2003,55(1):25-31.
[16] CONTI E,MULLER C W,STEWART M.Karyopherin flexibility in nucleocytoplasmic transport[J].Curr Opin Struct Biol,2006,16(2):237-244.
[17] SAPORITA A J,ZHANG Q,NAVAI N,et al.Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor[J].J Biol Chem,2003,278(43):41998-42005.
[18] ZHOU S,WANG X,DING J,et al.Increased ATG5 expression predicts poor prognosis and promotes EMT in cervical carcinoma[J].Front Cell Dev Biol,2021,9:757184.
[19] IRIE T,KIGAWA J,MINAGAWA Y,et al.Prognosis and clinicopathological characteristics of Ib-IIb adenocarcinoma of the uterine cervix in patients who have had radical hysterectomy[J].Eur J Surg Oncol,2000,26(5):464-467.
[20] LAMOUILLE S,XU J,DERYNCK R.Molecular mechanisms of epithelial-mesenchymal transition[J].Nat Rev Mol Cell Biol,2014,15(3):178-196.
[21] CULIG Z,SANTER F R.Androgen receptor signaling in prostate cancer[J].Cancer Metastasis Rev,2014,33(2-3):413-427.
[22] HUO C,KAO Y H,CHUU C P.Androgen receptor inhibits epithelial-mesenchymal transition,migration,and invasion of PC-3 prostate cancer cells[J].Cancer Lett,2015,369(1):103-111.
[23] ZHU M L,KYPRIANOU N.Role of androgens and the androgen receptor in epithelial-mesenchymal transition and invasion of prostate cancer cells[J].FASEB J,2010,24(3):769-777.
[24] MA Z F,WEI L,ZHANG W,et al.The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells[J].BMC Biochem,2015,16:13.
[25] FIZAZI K.The role of Src in prostate cancer[J].Ann Oncol,2007,18(11):1765-1773.
[26] JC Z,LE L,VV S,et al.Androgen receptor non-nuclear regulation of prostate cancer cell invasion mediated by Src and matriptase[J].Oncotarget,2015,6(9):6862-6876.
[27] YANG L,XIE S,JAMALUDDIN M S,et al.Induction of androgen receptor expression by phosphatidylinositol 3-kinase/Akt downstream substrate,FOXO3a,and their roles in apoptosis of LNCaP prostate cancer cells[J].J Biol Chem,2005,280(39):33558-33565.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录