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[喉癌肿瘤基质中HIF-1α和COX-2表达分析及其与肿瘤侵袭程度的相关性——初步研究]

[Analysis of HIF-1α and COX-2 expression in tumor stroma and correlation with the degree of neoplasm invasiveness in laryngeal cancer--preliminary study].

作者信息

Woś Jan, Bryś Magdalena, Lewy-Trenda Iwona, Stasikowska Olga, Papież Paweł, Papierz Wielisław, Starska Katarzyna

机构信息

Oddział Laryngologii Szpitala im. Żeromskiego w Krakowie.

出版信息

Otolaryngol Pol. 2011 Sep;65(5 Suppl):102-8. doi: 10.1016/S0030-6657(11)70717-X.

DOI:10.1016/S0030-6657(11)70717-X
PMID:22000259
Abstract

INTRODUCTION

Despite extensive research in the field of molecular biology, immunology and histopathology, prognostically unambiguous morphological indicators of the invasiveness of tumor which allow the prediction of disease course in laryngeal cancer have not yet been identified. The aim of this study was to analyze gene and protein expression of HIF-1a and COX-2 in the tumor stroma and to find relationships between clinical and morphological features (pT, G, depth of tumor invasion, plasmalymphocytic infiltration) and certain markers in squamous cell laryngeal carcinoma.

MATERIAL AND METHODS

We analyzed a group of 59 patients with verified squamous cell carcinoma of the larynx. The pathological evaluation was included pTNM classification criteria, depth of invasion according to tumor front grading and degree of morphological differentiation. Quantitative analysis of the amplified product in real time (real-time RT2-PCR) for estimation of mRNA HIF-1a and COX-2 expression in tumor cells were used. The level of HIF-1a and COX-2 protein expression by Western blot analysis was determined.

RESULTS

In studied group of laryngeal cancers significant differences in expression of certain molecules analyzed in tumor tissue and noncancerous epithelium of the larynx have been shown. Increased expression of HIF-1a and COX-2 at both mRNA and protein level was indicator of greater aggressiveness of the tumor, evaluated on the basis of clinical and morphological features in laryngeal squamous cell carcinomas. Tumors with the most invasive growth (pT4 stage, low-differentiated tumors G3, neoplastic infiltration with invasion of cartilage of the larynx) had the highest expression of HIF-1a and COX-2 at the mRNA and protein level.

CONCLUSIONS

The study pointed out the direction for further research to find unambiguous indicators for estimation of tumor invasiveness and the possibility of practical use of HIF-1a and COX-2 mRNA and protein level assessment as important methods for determining the advancement of clinical and morphological changes in laryngeal cancer, thereby selecting an appropriate model of treatment.

摘要

引言

尽管在分子生物学、免疫学和组织病理学领域进行了广泛研究,但尚未确定能够预测喉癌病程的、在预后方面明确无误的肿瘤侵袭性形态学指标。本研究的目的是分析肿瘤基质中HIF-1α和COX-2的基因和蛋白表达,并找出临床和形态学特征(pT、G、肿瘤浸润深度、浆淋巴细胞浸润)与喉鳞状细胞癌某些标志物之间的关系。

材料与方法

我们分析了一组59例经证实的喉鳞状细胞癌患者。病理评估包括pTNM分类标准、根据肿瘤前沿分级的浸润深度和形态学分化程度。采用实时定量分析扩增产物(实时RT2-PCR)来估计肿瘤细胞中mRNA HIF-1α和COX-2的表达。通过蛋白质印迹分析确定HIF-1α和COX-2蛋白表达水平。

结果

在研究的喉癌组中,已显示出在肿瘤组织和喉非癌上皮中分析的某些分子表达存在显著差异。基于喉鳞状细胞癌的临床和形态学特征评估,HIF-1α和COX-2在mRNA和蛋白水平的表达增加是肿瘤侵袭性更强的指标。具有最具侵袭性生长的肿瘤(pT4期、低分化肿瘤G3、伴有喉软骨浸润的肿瘤浸润)在mRNA和蛋白水平上HIF-1α和COX-2的表达最高。

结论

该研究指出了进一步研究的方向,以寻找评估肿瘤侵袭性的明确指标,以及将HIF-1α和COX-2 mRNA和蛋白水平评估作为确定喉癌临床和形态学变化进展的重要方法进行实际应用的可能性,从而选择合适的治疗模式。

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