肖意贵,郭桂兰

子宫内膜癌（Endometrial Cancer，简称EC）是最常见的一种妇科恶性肿瘤，好发于绝经后女性，全世界患病人数逐年呈上升趋势。这种癌症起源于子宫内膜上皮细胞，其发病率和死亡率在女性恶性肿瘤中均名列前茅，对女性的健康和生命构成了严重威胁。其发病率随着时间的推移而增加，严重威胁妇女的健康与生存。大多数女性以绝经后阴道不规则出血为主要症状。以往，在临床实践中，有症状的妇女通过包括经阴道镜、子宫内膜活检和宫腔镜在内的检查进行诊断。近年来，多项研究证明Ki-67和P16作为重要的细胞增殖和肿瘤抑制标志物，在子宫内膜癌的诊断、预后评估和治疗中发挥着关键作用。本综述主要阐述子宫内膜癌与各种免疫组化因子的关系，Ki-67及P16的生物学功能，及其与子宫内膜癌的分期和病理特征的相关性，让妇科医生更好地适应手术分期和辅助治疗提供理论依据。

子宫内膜癌；Ki-67；p16

[1] Dylan M Glubb,Deborah J Thompson,Katja K H Aben,et al.Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.[J].Cancer Epidemiology,Biomarkers& Prevention:a Publication of the American Association for Cancer Research,Cosponsored By the American Society of Preventive Oncology,2020,30(1):217-228. [2] Nicoletta Colombo,Carien Creutzberg,Frederic Amant,et al.ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis,Treatment and Follow-up.[J].International Journal of Gynecological Cancer:Official Journal of the International Gynecological Cancer Society,2016,26(1):2-30. [3] Kelechi Njoku,Joanna Abiola,Johanna Russell,et al.Endometrial cancer prevention in high-risk women.[J].Best Practice&Research. Clinical Obstetrics&Gynaecology,2019,65:66-78. [4] Menon,Sunil Sankunny et al.“Ki-67 protein as a tumour proliferation marker.”Clinica chimica acta;international journal of clinical chemistry vol.491(2019):39-45. [5] Uxa,Sigrid et al.“Ki-67 gene expression.”Cell death and differentiation vol.28,12(2021):3357-3370. [6] Risberg,Björn et al.“Dissociated expression of Bcl-2 and Ki-67 in endometrial lesions:diagnostic and histogenetic implications.”International journal of gynecological pathology:official journal of the International Society of Gynecological Pathologists vol.21, 2(2002):155-60. [7] Ghalib Farhood,R,and I Abd Ali Al-Humairi.“Immunohistochemical Study of Ki-67 in Hyperplastic and Endometrium Carcinoma:A Comparative Study.”Archives of Razi Institute vol.77,1 229-234.28 Feb.2022. [8] Jia,Mingzhu et al.“The Potential Value of Ki-67 in Prognostic Classification in Early Low-Risk Endometrial Cancer.”Cancer control:journal of the Moffitt Cancer Center vol.30(2023):10732748231206929. [9] Gerdes,J et al.“Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.”Journal of immunology(Baltimore,Md.:1950)vol.133,4(1984):1710-5. [10] Taghipour,Zahir,Shokouh,et al.Interrelationships Between Ki67,HER2/neu,p53,ER,and PR Status and Their Associations With Tumor Grade and Lymph Nod Involvement in Breast Carcinoma Subtypes:Retrospective-Observational Analytical Study.[J].Medicine, 2015, 94(32):e1359. [11] 贾如江,侯丽艳,尹清臣.轴突诱导因子4D和Ki67在胰腺癌中的表达及其与临床病理特征的关系[J].临床肝胆病杂志, 2018,34(1):4. [12] Kosmas K,Stamoulas M,Marouga A,et al.Expression of ki‐67 as proliferation biomarker in imprint smears of endometrial carcinoma.Diagnostic Cytopathology,2013,41(3).KM Pozharisskiĭ,Samsonova E A,Ten V P,et al.[Immunohistochemical profile of endometrioid adenocarcinoma of the uterus:ER,PR,HER-2,Ki-67 and their prognostic value].[J].Arkhiv Patologii,2005,67(2). [13] Stefansson IM,Salvesen HB,Immervoll H,et al.Prognostic impact of histological grade and vascular invasion compared with tumour cell roliferation in endometrial carcinoma of endometrioid type[J].Histopathology.,2004,44(5):472-479. [14] Suthipintawong C,Wejaranayang C,Vipupinyo C.Prognostic Significance of ER,PR,Ki67,c-erb B-2,and p53 in Endometrial Carcinoma[J].J Med Assoc Thai,2008,91(12):1779-1784. [15] Lax SF,Pizer ES,Ronnett BM,et a1.Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67,estrogen,and progesterone receptor expression[J].Hum Pathol,1998,29(6):551–558. [16] Nielsen AL,Nyholm HC.The combination of p53 and age predict cancer specific death in advanced stage(FIGO Ic-IV)of endometrial carcinoma of endometrioid type.An immunohistochemical examination of growth fraction:Ki-67,MIB-1 and PC10;suppressor oncogene protein:p53;oncogene protein:p185 andage,hormon [17] Ferrandina G,Ranelletti FO,Gallotta V,et al.Expression of cyclooxygenase-2(COX-2),receptors for estrogen(ER),and progesterone(PR), p53,ki67,and neu protein in endometrial cancer[J].Gynecol Oncol,2005,98(3):383-389. [18] Kamb,Aruis NA,eaver-Feldhaus J,et al.A cell cycle regulatory potentially involved in gene-sis of many tumor types[J].Science, 1994,264(5157):436. [19] 陈小贺.细胞周期素D1､p16基因与肿瘤相关性的研究[J].实用肿瘤学杂志,2006,20(1):76.1.2 p16与子宫内膜癌. [20] Bartkova J,Lukas J,Guldberg P,et a1.The p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis[J].Cancer Res,1996,56:5475-5483. [21] Khoo CM,Carrasco DR,Bosenberg MW,et al.INK4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse[J].Proc Natl Acad Sci USA,2007,104(10):3931-3936. [22] Gnatov A,Bischoff J,Schwarzenau C,et al.P16 alterations increase the metastaticpotential of endometrial carcinoma[J].Gynecol Oncol, 2008,111(2):365-371. [23] Wong YF,Chung TK,Cheung TH,et al.Methylation of p16ink4A in primarygynecologic malignancy[J].Cancer Lett,1999,136(2):231-235. [24] Engelsen IB,Stefansson I,Akslen LA,et a1.Pathologic expression of p53 or p16 in preoperative curettage specimens identifies high-risk endometrial carcinomas[J].Am J Obstet Gynecol.2006,195(4):979–986. [25] Ignatov A,Bischoff J,Schwarzenau C,et al.P16 alterations increase the metastatic potential of endometrial carcinoma[J].Gynecol Oncol,2008,111:365–371. [26] Kamb,Aruis NA,eaver-Feldhaus J,et al.A cell cycle regulatory potentially involved in gene-sis of many tumor types[J].Science, 1994,264(5157):436. [27] Cully M,You H,Levine AJ,et al.Beyond PTEN mutations:the PI3K pathway as an integrator of multiple inputs during tumorigenesis[J]. Nat Rev Cancer,2006,6(3):184. [28] Raftopoulou M,Etienne-Manneville S,Self A,et al.Regulation of cell migration by the codomain of the tumor suppressor PTEN[J]. Science,2004,303(5661):1179-1181. [29] Han SY,Kato H,Kato S,et al.Function evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay[J]. Cancer Res,2000,60(12):3147-3151. [30] Cerezo L,Cardenes H,Michael H.Molecular alterations in the pathogenesis of endometrial adenocarcinoma.Therapeutic imp lications[J].Clin TrainsOncol,2006,8(4):231-241. [31] Tamura M,Matsumoto K,Aota S,et al.Inhibition of cell migration,spreading and focall adhesions by tumor supp ressor PTEN[J]. Science,2004,280(5369):1614-1617. [32] Maehama T,Dixon JE.The tumor suppressor,PTEN/MMAC1,dephosphorylates the lipid second messenger, phosphatidylinosito l3,4,5-trisphosphate[J].J BioChem,1998,273:1337513378. [33] Attias-Geva Z,Bentov I,Kidron D,et al.p53 Regulates insulin-like growth factor-I receptor gene expression in uterine serous carcinoma and predicts responsiveness to an insulin-like growth factor-I receptor–directed targeted therapy[J].Eur J Cancer,2012,48:1570-1580. [34] Bullock AN,Fersht AR.Rescuing the function of mutant P53[J].Nat Bey Cancer.,2001,1(1):68-76. [35] Dobrzycka B,Terlikowski SJ,Mazurek A,et al.Circulating freeDNA,p53 antibody and mutations of KRAS gene in endometrialcancer[J]. Int J Cancer,2010,127(3):612-621. [36] Elhafey AS,Papadimitriou JC,EI-Hakim MS,et al.Computerized image analysis of p53 and proliferating cell nuclear antigen expression in benign,hyperplastic,and malignant endometrium[J].Arch Pathol Lab Med,2001,125(7):872-879. [37] Mariani A,Sebo TJ,Katzmarm JA,et a1.Endometrial cancer;can nodal status bepredicted with curettage[J]?Gynecol Oncol,2005, 96(3):594-600. [38] Ragni N,Ferrero S,Prefumo F,et al.The association between P53 expression,stageand histological featuers in endometrial cancer[J].Eur J Obstet Gynecol Reproud Biol,2005,123(1):111-116. [39] 何畏,魏丽慧,卞度宏,等.子宫内膜腺癌p53蛋白与基因突变的研究[J].重庆医科大学学报,2000,25(4):362-364.

点击下载PDF