p53抑癌基因在腺样囊性癌中的作用

腺样囊性癌是头颈部较常见的恶性肿瘤之一,其特点为嗜神经性及远处转移,手术和放化疗效果及预后较差,为了提高患者的远期生存率,迫切需要寻找新的治疗方法,而p53基因是一种重要的抑癌基因,近年来在恶性肿瘤中的作用日益受到重视,因此可作腺样囊性癌治疗的重要途径来探讨。     

Metallothionein immunostaining in adenoid cystic carcinomas of the salivary glands

Metallothionein (MT) is a protein that has been studied in several tumors as a prognostic factor and as a potential myoepithelial cell marker in breast cancer. The aims of this study were to assess the immunohistochemical staining of MT in adenoid cystic carcinomas of the salivary glands (ACC), and to analyze possible morphological and quantitative variations among the solid, cribriform, and tubular histological subtypes. MT was investigated in 15 cases of ACC using the immunohistochemical technique. All of the cases expressed the MT antigen. This expression was noteworthy in cells depicting myoepithelial differentiation. ACC with predominant tubular pattern presented a significantly lower mean index of MT immunopositivity than did solid or cribriform subtypes, while these two latter groups did not differ in terms of MT expression. Our results suggest that MT may be an important tool for immunolocalization of myoepithelial tumor cells in salivary gland neoplasms.     

抑癌基因甲基化与涎腺腺样囊性癌

抑癌基因甲基化是当前肿瘤研究的热点领域,它涉及细胞周期调控、细胞间信号转导、DNA凋亡及肿瘤的侵袭转移等过程.抑癌基因甲基化与涎腺腺样囊性癌的发生及其生物学行为密切相关.     

E钙粘素在涎腺腺样囊性癌中的表达及其意义

背景与目的:近年来关于上皮型钙粘素与肿瘤关系的研究比较多,但不同研究得到的结果差异较大,而且近年来的研究显示,E钙粘素在肿瘤转移过程中的作用可能具有多面性.本文旨在研究E钙粘素在涎腺腺样囊性癌中的表达水平,探讨E钙粘素与涎腺腺样囊性癌的神经侵犯、局部复发、远处转移以及预后的关系.方法:采用免疫组化技术检测55例涎腺腺样囊性癌组织标本和20例正常涎腺组织中E钙粘素的表达.应用Kaplan-Meier法进行生存分析,组间比较用log-rank检验,两组比率的比较采用χ2检验.结果:本组患者的5年和10年生存率分别为78.2%和51.4%:E钙粘素在正常涎腺组织中的阳性率(90.0%)显著高于涎腺腺样囊性癌组织(63.6%)(P＜0.05);E钙粘素在有神经受侵、局部复发及远处转移者的肿瘤组织中的阳性率(50.0%、52.4%及47.8%),均低于无神经受侵、无局部复发及无远处转移者(71.4%、70.6%及75.0%).结论:E钙粘素在涎腺腺样囊性癌组织中表达下调;其表达水平与神经侵犯、局部复发及发生远处转移相关.     

p16和p53抑癌基因产物在胰腺癌中表达的研究

目的 :探讨抑癌基因p16和p53在胰腺癌中的表达与临床病理的关系及其在胰腺癌发病机制中所起作用。方法 :应用免疫组织化学方法检测 50例胰腺癌p16和p53蛋白的表达水平。结果 :p16蛋白表达阳性率为 4 8% ,组织学Ⅰ级阳性率 (80 % )显著高于Ⅱ级 (50 % )和Ⅲ级 (2 5% ) ;临床Ⅰ期阳性率 (80 % )显著高于Ⅱ期 (38 9% )和Ⅲ Ⅳ期 (2 9 4 % )。p53蛋白表达阳性率为 54% ,临床Ⅰ期阳性率(2 6 7% )却显著低于Ⅱ期 (6 1 1% )和Ⅲ Ⅳ期 (70 6 % )。p16发生缺失同时伴有p53基因突变 ,即p16(- )p53( )共 17例 ,占 34%。结论 :胰腺癌发生中存在p16抑制途径和p53抑制途径改变 ,p16和p53蛋白异常在胰腺癌发生进展中起着重要作用。     

p53 tumor suppressor gene and ras oncogene mutations in hypopharyngeal squamous cell carcinomas

To examine the potential role of p53 and ras gene mutations in hypopharyngeal tumorigenesis, twenty-eight primary hypopharyngeal carcinomas, obtained at biopsy or total pharyngolaryngectomy, were investigated. Exons 5 through 9 of the p53 gene and exons 1 and 2 of the H-, K-, N-ras gene were screened using a combination of immunohistochemistry and single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP). The targeted DNA sequences coding for p53 and ras were confirmed by direct DNA sequencing. Point mutations of p53 were found in 9 (32.1%) of the 28 cases, including one with a double mutation, 3 in exon 5, 1 in exon 6, 2 in exon 7 and 4 in exon 8. Positive nuclear immunostaining for p53 was evident in 14 (50.0%) lesions. Seven (25.0%) of the 28 demonstrated point mutations in the H-rns gene, and 11 (39.3%) showed positive cytoplasmic staining for I as. The 5-year survival rate was worse with than without p53 overexpression (p <0.05). The present results suggest that gene mutations, although they occur at a relatively low incidence, are involved in hypopharyngeal tumorigenesis with p53 expression being a prognostic factor.     

Twist在涎腺腺样囊性癌中的表达及其临床意义

目的 探讨转录因子Twist在涎腺腺样囊性癌中的表达水平及其与各临床病理因素的关系.方法 采用免疫组化方法检测48例涎腺腺样囊性癌、18例多形性腺瘤和10正常腮腺组织中Twist蛋白的表达情况,分析Twist表达与腺样囊性癌临床病理因素的关系.结果 Twist在涎腺腺样囊性癌组织中的表达水平明显高于多形性腺瘤和正常腮腺组织(P<0.05).Twist表达与腺样囊性癌的病理分型、嗜神经侵袭、术后复发及远位转移有相关性(P<0.05).结论 Twist蛋白表达可能与涎腺腺样囊性癌的分化调节、嗜神经侵袭及远位转移有关.检测Twist的表达水平对判断腺样囊性癌患者的预后有一定的参考价值.     

Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid cystic carcinomas of the salivary gland

This study examined the immunohistochemical expression of carbohydrate antigens CA19-9 and CA125 and their relationship to various biological parameters in 27 mucoepidermoid carcinomas (MEC) and 18 adenoid cystic carcinomas (ACC) arising from salivary glands. The series showed higher immunopositivity for CA125 (67% for MEC; 33% for ACC) than for CA19-9 (59% for MEC; 11% for ACC). CA19-9 epitope was mainly expressed in cystic (MEC) and cribriform/tubular (ACC) components of carcinoma tissues. Solid components in MEC occasionally showed positive staining for CA19-9. CA125 was evenly expressed in both ACC and MEC tissues regardless of their different histological components. The positive expression of CA19-9 and CA125 in the carcinoma tissues did not influence the clinical course of patients with MEC and ACC. A significant relationship was only demonstrated between the immunohistochemical expression of CA125 and the low proliferative activity (LI) evaluated by Ki-67 immunohistochemistry. However, no significant relationship was found between LI and the patients' clinical course. These results suggest that the immunostaining for CA19-9 and CA125 provide no reliable data to predict the clinical course of patients with MEC and ACC of the salivary glands.     

Mutations in the p53 tumor suppressor gene in human cutaneous squamous cell carcinomas.

In this study, we analyzed 10 human squamous cell carcinomas (SCCs) for alterations in the p53 tumor suppressor gene in exons 4 through 9 by single-strand conformation polymorphism (SSCP) analysis. We found that 2 of 10 SCCs displayed unusual SSCP alleles at exon 7 of the p53 gene. Subsequent cloning and sequencing of PCR-amplified exon 7 DNA from these two tumors revealed that one had a G----A transition at the first position of codon 244, predicting a glycine-to-serine amino acid change, while the other tumor exhibited a G----T base change at the second nucleotide of codon 248, predicting an arginine-to-leucine substitution. Because the mutations in the p53 tumor suppressor gene in both tumors were located opposite potential pyrimidine dimer sites (C-C), it is consistent with these mutations having been induced by the ultraviolet radiation present in sunlight. These studies demonstrate that inactivation of the p53 tumor suppressor gene, as well as activation of ras oncogenes, may be involved in the pathogenesis of some human skin cancers.     

Estrogen receptor expression in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma

Estrogen receptor (ER) expression in salivary gland carcinomas is controversial, and most published studies considered no more than 10 cases. We analyzed ER expression by immunohistochemistry in 136 mucoepidermoid carcinomas and 72 adenoid cystic carcinomas. All cases were negative. These results do not support a role for estrogens in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma.     

涎腺腺样囊性癌中丝裂原激活蛋白激酶p38的表达及意义

目的 探讨丝裂原激活蛋白激酶p38(p38MAPK)在涎腺腺样囊性癌(SACC)中的表达及临床意义.方法 采用组织微阵列平台,运用免疫组化和原位杂交技术,检测52例SACC和11例正常涎腺组织中p38MAPK蛋白和mRNA的表达,并分析其与SACC 临床病理特征的关系.结果 正常涎腺组织和SACC组织中,p38MAPK蛋白的阳性表达率分别为36.4%和96.2%,差异有统计学意义(P＜0.01).p38MAPK蛋白表达与SACC的淋巴结转移、神经侵犯有关(均P＜0.05).正常涎腺组织和SACC组织中,p38MAPK mRNA的阳性表达率分别为45.5%和94.2%,差异有统计学意义(P＜0.01).p38MAPK mRNA表达与SACC的淋巴结转移、神经侵犯有关(均P＜0.05).SACC组织中,p38MAPK蛋白与mRNA的表达呈正相关(r=0.409,P＜0.01).结论 在SACC组织中,p38MAPK表达上调,p38MAPK通路可能与SACC的发生、侵袭和转移有关.

Abstract：

Objective To investigate the expression of p38 mitogen-activated protein kinase (p38MAPK) in salivary adenoid cystic carcinoma (SACC) tissues and their clinicopathologic significance.Methods The protein and mRNA expressions of p38MAPK were examined by immunohistochemistry and in situ hybridization, respectively, in 52 cases of SACC and in 11 normal salivary gland tissues adjacent to the tumors on a tissue microarray platform.Results The positive rate of p38MAPK protein expression in the paracancerous normal salivary gland tissues and that in SACC were 36.4% and 96.2%, respectively,showing a significant statistical difference (P ＜ 0.01 ).The protein expression of p38MAPK was positively correlated with the lymph node metastasis and nerve involvement (P ＜ 0.05 ).The positive rates of p38MAPK mRNA in the paracancerous tissues and in the SACC tissues were 45.5% and 94.2%,respectively, with a significant statistical difference (P ＜0.01 ).The mRNA expression of p38MAPK was positively correlated with the lymph node metastasis and nerve involvement (P ＜ 0.05 ).In the SACC, there was a notable positive correlation between the p38MAPK protein and mRNA expressions (r = 0.409, P ＜0.01).Conclusions The expression of p38MAPK is up-regulated in salivary adenoid cystic carcinoma.p38MARK may be involved in the tumorigenesis, development and metastasis of this cancer.     

H-ras gene mutations in salivary gland mucoepidermoid carcinomas

BACKGROUND: The authors' recent investigation of salivary gland tumors in ras gene alteration has suggested that K-ras activation may not play a role in their oncogenesis but H-ras may, especially in mucoepidermoid carcinomas. A study was undertaken to assess the overall incidence of mutated H-ras genes in mucoepidermoid carcinomas and to discover its potential correlation with clinicopathologic parameters. METHODS: Fifty samples from patients with salivary gland mucoepidermoid carcinoma were analyzed for point mutations at codons 12, 13, and 61 of the H-ras gene using the polymerase chain reaction followed by automated direct sequencing methodology. RESULTS: Mutated H-ras genes were detected in 9 patients, for an overall incidence of 18% (9 of 50 patients). All but 1 of the mutations occurred at codon 12: a GGC-to-GTC transversion in 8 patients and a GGC-to-GAC transition in 1 patient, resulting in the amino acid substitution of valine and aspartic acid, respectively, for glycine. One of the samples showed concurrent mutations at codons 12 (GGC-to-GTC) and 13 (GGT-to-GGA). None of the samples demonstrated mutations involving codon 61. The H-ras mutations were observed in 5% (1of 21), 17% (2 of 12), and 35% (6 of 17) of low, intermediate, and high grade lesions, respectively. CONCLUSIONS: These data suggest involvement of H-ras activation in conjunction with other yet-unknown events in the development and/or progression of mucoepidermoid carcinomas. It is noteworthy that a stepwise increase in the frequency of H-ras mutations strongly correlates with tumor grade (P = 0.017). Molecular analysis of this gene alteration may provide assistance in the determination of tumor grade and differentiation.     

Histologic grading of adenoid cystic carcinoma of the salivary glands

Seventy-nine patients with adenoid cystic carcinoma arising in salivary glands were studied to determine whether a correlation existed between the morphologic features of the tumor and the prognosis. Three histologic grades were established: Grade I, tumors with tubular and cribriform areas but without solid components; Grade II, cribriform tumors that were either pure or mixed with less than 30% of solid areas; and Grade III, tumors with a predominantly solid pattern. Cumulative survival rates at 15 years were 39%, 26%, and 5%, for Grades I, II, and III, respectively. Grade III tumors were larger, recurred frequently, and killed the patients within 4 years. Grade I lesions were smaller, were amenable to complete surgical excision, and had a protracted clinical course. Grade II tumors lay between the other two forms both clinically and pathologically. Other important prognostic features of the adenoid cystic carcinoma were its primary site, its presence or absence at surgical margins, and the anatomic structures it involved.     

Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung.

Aberrations of the p53 gene in 115 surgical specimens of non-small cell carcinomas of the lung were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products. Structural abnormalities of the p53 gene were observed in 60 tumors (52%), i.e., 8 of 14 large cell carcinomas, 24 of 58 adenocarcinomas, 25 of 37 squamous cell carcinomas, and 3 of 6 adenosquamous carcinomas. Direct sequencing of abnormal DNA fragments revealed 45 single-base substitutions, 9 deletions or insertion of a short nucleotide sequence, and 3 two-base substitutions in 57 tumors. In the other 3 tumors, loss of one of the p53 alleles was observed, with no mutation in the other allele. Allelic loss of the p53 gene was observed in 14 of 43 informative cases (33%), and in 11 of the 14 cases the remaining allele was mutated. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage. Their high frequency suggests that they were involved in the genesis of non-small cell carcinomas of the lung. The mutation frequency (46%) of the p53 gene in tumors carrying mutated ras genes was essentially the same as the overall frequency in lung cancers, suggesting that accumulation of mutations in these two genes in a tumor is a random phenomenon.