肺鳞状细胞癌中Notch1～4和DLL4的表达及与微血管密度的相关性

摘要

Purpose To determine the intratumoral and stromal expression of Notch 1,2,3 ,4 and DLL4 in lung squamous cell carcinoma ( SCC ), and to evaluate their clinical significances and correlations with microvessel density ( MVD ). Methods Immunohisto-chemistry was used to examine the expression of Notch 1,2,3,4 and DLL4 in 64 cases of SCC and their adjacent lung tissue samples. MVD in SCC was measured by CD31 immunohistochemical staining. Results Intratumoral expression of Notch 1-4 and DLL4 in SCC was significantly up-regulated as compared with bronchial epithelia in adjacent nontumor lung tissues ( P < 0. 05 ), with Notchl, Notch3 and DLL4 positively correlated with tumor size ( r = 0. 334, 0. 421, 0. 475 , respectively, P < 0. 05 ) and Notchl and Notch2 positively associated with lymph node metastasis of SCC ( r = 0. 356, 0.417, respectively, P < 0. 05 ). Notch 1,2,3 expression showed no significant differences between the stroma of SCC and that of adjacent lung tissues ( P > 0. 05 ), while stromal Notch 4 and DLL4 expression were not only significantly higher in SCC tissues than that in adjacent nontumor lung tissues ( P < 0. 05 ), but also positively related to tumor size ( r = 0. 300, 0. 440, respectively, P < 0. 05 ) and clinical stage of SCC ( r = 0. 365 , 0. 336, respectively, P < 0. 05 ). Intratumoral expression of DLL4 and stromal expression of DLL4 and Notch4 were inversely correlated with MVD ( r = - 0. 285 , - 0. 323 , - 0. 258 , respectively, P < 0. 05 ). Conclusion Intratumoral and stromal expression of Notch and DLL4 not only promotes the progress of SCC, but also plays an important role in regulating the angiogenesis of SCC.%目的 探讨Notch1～4及DLL4在肺鳞状细胞癌肿瘤细胞和间质中表达的临床病理意义及与微血管密度的相关性.方法 免疫组化SP法检测64例肺鳞癌和癌旁非肿瘤肺组织中Notch1～4及DLL4的表达,免疫组化SP法检测CD31计数肺鳞癌的微血管密度.结果 (1)肺鳞癌肿瘤细胞内Notch1～4及DLL4的表达明显高于癌旁支气管黏膜上皮(P＜0.05),其中Notch1、3和DLL4的表达与肿瘤的大小呈正相关(r=0.334、0.421、0.475,P＜0.05),Notch1与Notch2的表达与肿瘤淋巴结转移呈正相关(r=0.356、0.417,P＜0.05);(2)肺鳞癌间质及癌旁肺间质中Notch1～3的表达无明显差异(P＞0.05),而Notch4与DLL4在肺鳞癌间质中的表达明显高于癌旁肺间质(P＜0.05),且与肿瘤大小(r=0.300、0.440,P＜0.05)及临床分期(r=0.365、0.336,P＜0.05)呈正相关;(3)肿瘤细胞中DLL4及间质内DLL4、Notch4的表达与肺鳞癌的微血管密度呈负相关(r=-0.285、-0.323、-0.258,P＜0.05).结论 肺鳞癌肿瘤细胞和间质中Notch与DLL4的表达可能促进肿瘤发展,并对肿瘤血管的生成具有重要的调控作用.