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目的探讨诱导凋亡的第二信使神经酰胺(ceramide)在喉组织癌前病变向喉癌转化过程中的作用。方法采用回顾分析的方法,取复旦大学附属眼耳鼻喉科医院1991-2001年间声带白斑的病例178例,找出相应的石蜡块,其中转化为喉癌的31例。采用流式细胞仪技术和免疫组化法分析这31例的喉正常黏膜标本(取自喉癌旁的正常组织)、癌前病变时的标本和喉癌组织标本中DNA倍体情况及神经酰胺的表达情况(400倍视野下染色阳性细胞计数×100)。结果31例喉正常黏膜标本均为DNA二倍体; 31个声带白斑标本中3个为DNA二倍体, 28个为DNA异倍体; 31个喉癌标本均为DNA异倍体。31例患者的喉正常黏膜、声带白斑、喉癌标本中神经酰胺的表达依次减少,分别为每400倍视野下阳性表达细胞数( x±s,以下同) ( 400±30 )个、( 180±20 )个、( 10±10 )个,t检验差异有统计学意义(P<0 01)。二倍体细胞内神经酰胺的阳性表达数(400±20)个,明显高于异倍体细胞内(150±10)个,t检验差异有统计学意义(P<0 01)。结论喉组织癌前病变向喉癌转化过程中,神经酰胺起到非常重要的作用。提示诱导凋亡的第二信使神经酰胺逐渐减少可能是喉组织癌变过程中的关键因素之一。
Objective To investigate the role of ceramide, a second messenger cell inducer of apoptosis, in the transformation of laryngeal precancerous lesions into laryngeal carcinomas. Methods Retrospective analysis of the method taken from the Department of Otolaryngology Hospital Fudan University during 1991-2001 178 cases of vocal cord leukoplakia, to identify the corresponding paraffin block, which converted into laryngeal cancer in 31 cases. Flow cytometry and immunohistochemistry were used to analyze the DNA ploidy in 31 cases of laryngeal normal mucosa (normal tissue taken from laryngeal cancer), precancerous lesion and laryngeal cancer tissues, (400 times the visual field staining positive cell count × 100). Results 31 cases of laryngeal normal mucosa specimens were DNA diploid; 31 vocal cord leukoplakia specimens of three DNA duplexes, 28 DNA aneuploidy; 31 laryngeal cancer specimens were DNA aneuploidy. The expression of ceramide in normal laryngeal mucosa, vocal cord leucorrhea and laryngeal carcinoma were decreased in 31 cases, which were respectively (400 ± 30) × (400 ± 30) × ± 20), (10 ± 10), t test was statistically significant (P <0.01). The positive number of ceramide in diploid cells was (400 ± 20), which was significantly higher than that in aneuploid cells (150 ± 10). There was significant difference in t test (P <0.01). Conclusions Ceramide plays a very important role in the conversion of laryngeal precancerous lesions to laryngeal cancer. It is suggested that the decrease of ceramide, a second messenger of apoptosis, may be one of the key factors in carcinogenesis of laryngeal tissues.