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上埃及地区肾细胞癌中冯·希佩尔-林道肿瘤抑制蛋白、MET原癌基因和TFE3转录因子癌蛋白的表达模式

The expression pattern of Von Hippel-Lindau tumor suppressor protein, MET proto-oncogene, and TFE3 transcription factor oncoprotein in renal cell carcinoma in Upper Egypt.

作者信息

Nagi Fayed Mohamad, Omar Abd-Alhady Mohammad, Mostafa Mohamed Galal, Mohammed Eman Ahmed, Abd-Elwahed Hussein Mahmoud Rezk

机构信息

Pathology Department, Faculty of Medicine, Assuit University, Assuit, Egypt.

出版信息

Ultrastruct Pathol. 2011 Apr;35(2):79-86. doi: 10.3109/01913123.2010.544844.

Abstract

BACKGROUND

Genetic alterations in renal cell carcinoma (RCC) involve tumor suppressor genes such as Von Hippel-Lindau (VHL); proto-oncogenes such as MET and transcription factors such as TFE3 oncoprotein.

AIM

To examine the clinicopathologic features and the expression of some oncogenic molecules in various RCCs in patients from Upper Egypt.

MATERIALS AND METHODS

The authors examined the expression pattern of pVHL; MET; and TFE3 proteins in 59 RCC using immunoperoxidase staining methods. The study group consisted of clear cell RCCs (CRCC); papillary RCCs type 1 (PRCC1); papillary RCCs type 2 (PRCC2); Xp11-2 translocation RCCs (XP11.2RCC); chromophobe RCCs (ChRCC); and sarcomatoid RCCs (SRCC).

RESULTS

Variations were found in the expression of these molecules in the different types of RCCs. The mean age of RCCs among Egyptians was 52.70 ± 1.73 years; with male sex predominance. Mass lesion; pain; and hematuria were the main presenting features. Metastatic disease was more frequent with CRCC variant. pVHL expression was strong in PCRCC2; Xp11.2RCC; and ChRCC; moderate in CRCC; and weak in both PRCC1 and sarcomatoid RCC. MET protein expression was moderate in Xp11.2RCC; PRCC1; PRCC2; and sarcomatoid RCC. TFE3 protein expression was strong in Xp11.2RCC and PRCC2 variants. The expression was moderate in PRCC1; CRCC; ChRCC; and sarcomatoid RCC. Positive correlation was found in the expression of the different proteins (pVHL; MET; and TFE3) and some histological features (tumor grade; inflammation; necrosis and metastasis) and the presence of metastasis and some histological features (inflammation and/or necrosis).

CONCLUSIONS

This study provides the first indication about the clinicopathologic features of RCCs in Upper Egypt. The variable expression of these molecules in the different variants of RCC suggests that several oncogenic pathways are operational in their development.

摘要

背景

肾细胞癌(RCC)中的基因改变涉及肿瘤抑制基因,如冯·希佩尔-林道(VHL)基因;原癌基因,如MET基因;以及转录因子,如TFE3癌蛋白。

目的

研究埃及上埃及地区患者不同类型肾细胞癌的临床病理特征及一些致癌分子的表达情况。

材料与方法

作者采用免疫过氧化物酶染色法检测了59例肾细胞癌中pVHL、MET和TFE3蛋白的表达模式。研究组包括透明细胞肾细胞癌(CRCC)、1型乳头状肾细胞癌(PRCC1)、2型乳头状肾细胞癌(PRCC2)、Xp11-2易位性肾细胞癌(XP11.2RCC)、嫌色性肾细胞癌(ChRCC)和肉瘤样肾细胞癌(SRCC)。

结果

在不同类型的肾细胞癌中发现了这些分子表达的差异。埃及肾细胞癌患者的平均年龄为52.70±1.73岁,男性居多。肿块、疼痛和血尿是主要临床表现。透明细胞肾细胞癌变体发生转移的情况更常见。pVHL在2型乳头状肾细胞癌、Xp11.2易位性肾细胞癌和嫌色性肾细胞癌中表达强,在透明细胞肾细胞癌中表达中等,在1型乳头状肾细胞癌和肉瘤样肾细胞癌中表达弱。MET蛋白在Xp11.2易位性肾细胞癌、1型乳头状肾细胞癌、2型乳头状肾细胞癌和肉瘤样肾细胞癌中表达中等。TFE3蛋白在Xp11.2易位性肾细胞癌和2型乳头状肾细胞癌变体中表达强。在1型乳头状肾细胞癌、透明细胞肾细胞癌、嫌色性肾细胞癌和肉瘤样肾细胞癌中表达中等。发现不同蛋白(pVHL、MET和TFE3)的表达与一些组织学特征(肿瘤分级、炎症、坏死和转移)以及转移的存在和一些组织学特征(炎症和/或坏死)之间存在正相关。

结论

本研究首次提供了关于埃及上埃及地区肾细胞癌临床病理特征的线索。这些分子在不同肾细胞癌变体中的可变表达表明,在其发生发展过程中有多种致癌途径在起作用。

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