乳腺癌肿瘤出芽与肿瘤浸润淋巴细胞及患者预后的关系研究
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摘要
目的:研究肿瘤出芽与乳腺癌临床病理特征、肿瘤浸润淋巴细胞(TILs)以及患者预后的关系。方法:收集2012年1月～2016年12月于暨南大学附属第一医院行手术治疗的178例乳腺癌患者资料及肿瘤组织切片,显微镜下观察乳腺癌组织病理切片中肿瘤出芽和肿瘤浸润淋巴细胞水平,X~2检验分析肿瘤出芽水平与乳腺癌患者临床病理特征和TILs的关系,Log-rank检验分析肿瘤出芽水平与乳腺癌患者无病生存期和总生存期的关系。结果:高肿瘤出芽组患者淋巴结阳性数目多、组织性分级高、脉管癌栓更多;肿瘤出芽数较多的患者TILs的水平较低,而肿瘤出芽数较少的患者TILs水平较高;高肿瘤出芽患者比低肿瘤出芽患者预后较差。结论:乳腺癌肿瘤出芽水平与恶性程度高的临床病理指标密切相关,肿瘤出芽水平与TILs水平呈负相关,是影响乳腺癌预后的重要因素。
AIM: To investigate the relationship of tumor budding with clinicopathologic parameters,tumor-infiltrating lymphocytes( TILs) of tumor microenvironment and the prognosis in breast cancer patients. METHODS: A total of 178 HE section samples were collected from the breast cancer patients treated with surgery in the First Affilated Hospital of Jinan University during Jan. 2012 to Dec. 2016. The tumor budding and stromal tumor-infiltrating lymphocytes were observed under light microscope. The correlation of tumor budding with the clinicopathologic status and TILs were analyzed by X~2 test. Kaplan-Meier survival analysis and Log-rank test were used to estimate the disease-free survival( DFS) and overall survival( OS). RESULTS: High tumor budding level was associated with more positive lymph nodes,higher grade,and more lymphovascular invasion. In addition,the patients with higher tumor budding level showed fewer TILs,while the patients with lower tumor budding level had more TILs. Furthermore,the patients with higher tumor budding level had a worse disease-free survival and overall survival than those with lower tumor budding level. CONCLUSION: Tumor budding is significantly associated with adverse clinicopathological characteristics of breast cancer and negatively correlated with TILs. Therefore,tumor budding may serve as a potential biomarker to predict the prognosis of breast cancer.
AIM: To investigate the relationship of tumor budding with clinicopathologic parameters,tumor-infiltrating lymphocytes( TILs) of tumor microenvironment and the prognosis in breast cancer patients. METHODS: A total of 178 HE section samples were collected from the breast cancer patients treated with surgery in the First Affilated Hospital of Jinan University during Jan. 2012 to Dec. 2016. The tumor budding and stromal tumor-infiltrating lymphocytes were observed under light microscope. The correlation of tumor budding with the clinicopathologic status and TILs were analyzed by X~2 test. Kaplan-Meier survival analysis and Log-rank test were used to estimate the disease-free survival( DFS) and overall survival( OS). RESULTS: High tumor budding level was associated with more positive lymph nodes,higher grade,and more lymphovascular invasion. In addition,the patients with higher tumor budding level showed fewer TILs,while the patients with lower tumor budding level had more TILs. Furthermore,the patients with higher tumor budding level had a worse disease-free survival and overall survival than those with lower tumor budding level. CONCLUSION: Tumor budding is significantly associated with adverse clinicopathological characteristics of breast cancer and negatively correlated with TILs. Therefore,tumor budding may serve as a potential biomarker to predict the prognosis of breast cancer.
引文
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[12]Denkert C,Loibl S,Noske A,et al.Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer[J].J Clin Oncol,2010,28(1):105-113.
[13]Zlobec I,Lugli A.Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer:tumor budding as oncotarget[J].Oncotarget,2010,1(7):651-661.
[14]Tse JC,Kalluri R.Mechanisms of metastasis:epithelial-tomesenchymal transition and contribution of tumor microenvironment[J].J Cell Biochem,2007,101(4):816-829.
[15]Chen L,Gibbons DL,Goswami S,et al.Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression[J].Nat Commun,2014,5:5241.
[2]Ueno H,Murphy J,Jass JR,et al.Tumour‘budding’as an index to estimate the potential of aggressiveness in rectal cancer[J].Histopathology,2002,40(2):127-132.
[3]Lugli A,Karamitopoulou E,Panayiotides I,et al.CD8+lymphocytes/tumour-budding index:an independent prognostic factor representing a‘pro-/anti-tumour’approach to tumour host interaction in colorectal cancer[J].Br JCancer,2009,101(8):1382-1392.
[4]Salgado R,Denkert C,Demaria S,et al.The evaluation of tumor-infiltrating lymphocytes(TILs)in breast cancer:recommendations by an International TILs Working Group2015[J].Ann Oncol,2015,26(2):259-271.
[5]Hida AI,Ohi Y.Evaluation of tumor-infiltrating lymphocytes in breast cancer;proposal of a simpler method[J].Ann Oncol,2015,26(11):2351.
[6]Kai K,Kohya N,Kitahara K,et al.Tumor budding and dedifferentiation in gallbladder carcinoma:potential for the prognostic factors in T2 lesions[J].Virchows Arch,2011,459(4):449-456.
[7]Salhia B,Trippel M,Pfaltz K,et al.High tumor budding stratifies breast cancer with metastatic properties[J].Breast Cancer Res Treat,2015,150(2):363-371.
[8]Li X,Wei B,Sonmez C,et al.High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma[J].Hum Pathol,2017,66:222-229.
[9]Liang F,Cao W,Wang Y,et al.The prognostic value of tumor budding in invasive breast cancer[J].Pathol Res Pract,2013,209(5):269-275.
[10]Gujam FJ,McMillan DC,Mohammed ZM,et al.The relationship between tumour budding,the tumour microenvironment and survival in patients with invasive ductal breast cancer[J].Br J Cancer,2015,113(7):1066-1074.
[11]Adams S,Gray RJ,Demaria S,et al.Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials:ECOG 2197 and ECOG 1199[J].J Clin Oncol,2014,32(27):2959-2966.
[12]Denkert C,Loibl S,Noske A,et al.Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer[J].J Clin Oncol,2010,28(1):105-113.
[13]Zlobec I,Lugli A.Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer:tumor budding as oncotarget[J].Oncotarget,2010,1(7):651-661.
[14]Tse JC,Kalluri R.Mechanisms of metastasis:epithelial-tomesenchymal transition and contribution of tumor microenvironment[J].J Cell Biochem,2007,101(4):816-829.
[15]Chen L,Gibbons DL,Goswami S,et al.Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression[J].Nat Commun,2014,5:5241.