Effect of 9-cis-retinoic acid on oral squamous cell carcinoma cell lines

Epstein–Barr virus (EBV) has been well documented in the aetiology of nasopharyngeal carcinoma (NPC), although its role as well as the genetic basis in the genesis of NPC have not been elucidated. The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2 oncoprotein, has been reported in a high percentage of cases, and also in association with EBV. Proliferating cell nuclear antigen (PCNA) has also been shown to be increased in NPC, suggesting its association among the overexpression of p53 and bcl-2 oncoprotein. We undertook this study to evaluate the correlation among these abnormalities in the development of NPC. The expression of p53 protein, bcl-2 oncoprotein, and the level of PCNA were investigated by immunohistochemistry in 53 patients with NPC. Twenty tissue samples from these patients were studied for p53 gene mutations by single strand conformation polymorphism (SSCP) and DNA sequencing as well as EBV genomes by polymerase chain reaction. Among the 53 specimens, 42 (79%) showed expression of p53 protein and 40 (75%) gave positive result for bcl-2 oncoprotein. A significant association was found between p53 expression and bcl-2 oncoprotein (P=0.002; Fisher's exact test) with 68% of the patients showing coexpression of both markers. The PCNA labelling index in the 53 patients varied from 5% to 80%. High PCNA labelling index was frequently found in the patients with overexpression of p53 protein and bcl-2 oncoprotein. The PCNA index in patients with p53 expression was significant higher than in those without p53 expression (P=0.002). Of the 20 patients, p53 mutations were found in four cases. EBV genomes were detected in 14 cases of which 12 cases showed overexpression of both p53 and bcl-2 and one case with only p53 expression and one case with bcl-2 expression. EBV genomes were detected in two cases with p53 mutations. We conclude that EBV is the important etiologic factor in NPC which may be involved in p53 and bcl-2 overexpression. The mutant p53 protein is correlated to deregulation of PCNA. p53 mutations participate in a small proportion of the tumorigenesis.     

STAT3在鼻咽癌中的表达特征及其与bcl-2和LMP1表达的关系

目的:探讨鼻咽癌中信号传导和转录激活子3(STAT3)的表达特征及其与bcl2和EB病毒潜在膜蛋白1(LMP1)表达的关系。方法:采用原位杂交和免疫组化法分别检测62例鼻咽癌组织中EB病毒EBER1的表达和STAT3、bcl2和LMP1蛋白的表达。结果:鼻咽癌中EBER1阳性率为1000%(62/62);LMP1阳性率为613%(38/62);STAT3和bcl2阳性癌细胞占癌细胞总数的百分率跨度分别为50%~950%和0~1000%。STAT3与bcl2表达呈正相关,rs=0444,P=0000。STAT3与LMP1表达无显著相关性。结论:鼻咽癌细胞中STAT3呈持续表达状态(即异常激活状态)。STAT3的异常激活可能通过上调bcl2这一抗凋亡基因的表达,从而延长了鼻咽癌细胞的生存时间。     

Incidence and pathology of primary brain lymphoma in Hong Kong Chinese patients

Primary brain lymphoma (PBL) is an uncommon extranodal lymphoma. Its incidence is rapidly increasing in both immunocompromised and immunocompetent patients in Western countries. Eighteen cases of PBL were identified during a 16-year period among HIV negative patients in Queen Mary Hospital, Hong Kong. One case of post-transplantation lymphoproliferative disease (PTLD) was positive for Epstein Barr virus (EBV) encoded RNA (EBER) by in situ hybridization. All the remaining 17 immunocompetent cases were classified as diffuse large B-cell lymphoma, except for one case of Burkitt's lymphoma. EBER expression was negative in all 13 cases tested. Immunostaining for bcl-2 and bcl-6 was positive in 8/11 and 6/11 cases tested, with heterogeneous combination of expression and intensity. The incidence rate of PBL in immunocompetent patients was stable at 1.03 per million per year. The incidence of PBL in post transplantation (0.16%) and HIV related setting (0.29%) is also low in Chinese. PBL in Chinese patients is almost uniformly represented by EBV negative, diffuse large B-cell lymphoma, confined to the brain. However, the molecular pathogenesis may be heterogeneous.     

Molecular pathology parameters in human nasopharyngeal carcinoma

BACKGROUND: To derive a better understanding of the biologic behavior of nasopharyngeal carcinoma (NPC), the authors evaluated a number of molecular variables to address the hypothesis that p53 dysfunction in NPC is associated with Epstein-Barr virus (EBV), increased tumor angiogenesis, lower likelihood of apoptosis, and poorer clinical outcome. MATERIALS: The biopsy samples from 87 NPC patients were obtained and sections were made to detect EBV, using in-situ hybridization; the authors used immunohistochemistry to assess p53, p21(WAF1/CIP1) expression, and microvessel density count (MVD). In situ end labelling was used to evaluate apoptosis and necrosis. Analyses were conducted on the association between each of these variables as well as clinical outcome, including survival and local control. RESULTS: There was a highly significant association between EBV-encoded RNA (EBER) positivity with p53 over-expression in that only 1 out of 32 p53 over-expressing tumors was EBER negative, as opposed to 19 out of 48 p53 negative tumors being EBER negative (P = 0.001). In addition, EBER positivity was highly associated with World Health Organization (WHO) type 3 NPC, Asian/Chinese ethnicity, a lower apoptotic index, and p21 over-expression. p53 over-expression was associated with a higher MVD count. Controlling for age and nodal status, EBER positivity was associated with both improved overall survival (P = 0.02), and disease-free survival (P = 0.04). In contrast, the presence of tumor necrosis was associated with an inferior local control (P = 0.03). CONCLUSION: p53 protein was over-expressed in approximately one third of NPC samples in the current study, and this correlated significantly with the presence of EBER. Epstein-Barr virus status was also associated with WHO type 3 NPC, Asian/Chinese ethnicity, and induction of p21. The presence of EBV appeared to predict for improved survival, the mechanism of which remains to be elucidated in this biologically complex disease.     

鼻咽癌发生发展过程中EBER1表达的研究

目的：探讨ＥＢＶ与鼻咽癌发生发展的关系及其病理学意义。方法：应用原位杂交技术检测５０例鼻咽癌石蜡切片组织中ＥＢＥＲ１的表达及分布状况。结果：正常鼻咽粘膜上皮及其单纯性增生、鳞状化生上皮ＥＢＥＲ１表达均阴性,鼻咽癌组织中表达率为９８％（４９／５０）,且在转移灶中不丢失。鼻咽异型增生上皮亦可表达ＥＢＥＲ１阳性信号（１６／２０）,结论：ＥＢＶ与鼻咽癌关系密切,ＥＢＶ可能在鼻咽上皮的恶性转化过程中起重要作用,鼻咽上皮的异型性改变尤其是ＥＢＥＲ１阳性者可认为是癌前病变,随访监测可能有利于早期发现鼻咽癌。     

N2~3期鼻咽癌EGFR、VEGF、EBER表达与放化疗敏感性的关系

[目的]探讨N期鼻咽癌EGFR、VEGF、EBER表达与放化疗敏感性间的关系。[方法]采用免疫组织化学疗法研究143例经病理确诊的鼻咽癌患者组织EBER、EGFR和VEGF表达：定量PCR和酶联免疫吸附法（ELISA）检测92例N。期鼻咽癌患者血浆EB病毒游离DNA（EBV／DNA）、EGFR、VEGF的表达水平,并对92例NH期鼻咽癌随访2年。[结果]N期鼻咽癌EBER、EGFR及VEGF表达阳性牢分别为97．8％（90／92）、95．7％（88／92）和35．9％（33／92）。EBER表达与远处转移、复发及临床缓解相关,VEGF和EGFR表达强度与远处转移均呈正相关。期鼻嘲癌患者血浆EBV／DNA、EGFR、VEGF治疗前与同步放化疗后比较差异均有统计学意义（P均〈0．05）。血浆中EGFR和VEGF表达水平与远处转移相关。[结论]血浆和组织中EGFR和VEGF表达水平均可能与鼻咽癌远处转移相关。     

鼻咽癌EB病毒感染与p53、bcl-2蛋白异常表达

（目的）探讨EB病毒在鼻咽癌发病中的作用。（方法）应用免疫组化技术分别检测46例鼻咽癌中EB病毒潜在膜蛋白（LMP－1）、p53及bcl－2蛋白表达。（结果）LMP－1的阳性率为52．2％（24/46）；24例LMP－1阳性病例中p53阳性16例、bcl－2阳性20例，22例LMP－1阴性病例中P53和bcl－2阳性分别有15例和18例，两组间无明显差异（P＞0．05）。〔结论〕LMP一1对p53和bcl-2表达无明显影响。     

Bcl-2 proto-oncogene expression in epstein-barr-virus-associated nasopharyngeal carcinoma

The bcl-2 proto-oncogene product inhibits apoptosis. Increased levels of bcl-2 protein are associated with prolonged B-cell survival and have been demonstrated in a high proportion of follicular B-cell lymphoma. Recent studies have shown that bcl-2 protein expression in B cells immortalized by Epstein-Barr virus (EBV) in vitro is up-regulated by the EBV-latency-associated antigen, latent membrane protein (LMP) I. The epithelial malignancy, undifferentiated nasopharyngeal carcinoma (UNPC), has a well-established association with EBV and the tumour cells characteristically display a restricted latent viral phenotype including LMP I. This study has investigated the relationship between the presence of EBV DNA, EBV phenotypic profiles and bcl-2 protein expression in conventionally processed and cryopreserved samples of NPC using in situ hybridization, immunocytochemical and immunoblotting techniques. bcl-2 was detected in most (80%) samples of UNPC as well as in 1/3 samples of keratinizing NPC and 2/2 samples of nasopharyngeal adenocarcinoma. However, no close correlation was found between the presence of EBV DNA, and profiles for LMP I and bcl-2 protein expression in 45 UNPC. In addition, bcl-2 protein was shown to be selectively expressed in the basal compartment of normal nasopharyngeal epithelia. bcl-2 protein expression has not been reported previously in malignant tumours of epithelial origin. The findings in this study implicate a role for bcl-2 both in normal keratinocyte differentiation and in the pathogenesis of epithelial malignancy.     

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer.

Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB DO7), and 41 of these 144 p53-positive cases were also bcl-2 positive (28%) compared with 32 of the remaining 80 p53-negative cases (40%). Survival was significantly worse (P = 0.01) in the p53-positive cases. Bcl-2-positive cases, including patients in all Dukes'' stages, had a slightly better prognosis which was not statistically significant. However, cases at an early stage (Dukes'' stages A and B) and with negative p53 status, had a much better prognosis if they showed bcl-2 protein expression, suggesting that the bcl-2 status itself has an effect on prognosis (P = 0.01). Neither bcl-2 nor p53 alone was correlated with stage, but when examined by both p53 and bcl-2 status a group [bcl-2(+)/p53(-)] with better prognosis was defined. The last group was significantly lower Dukes'' stage, with 26 out of 32 cases (81%) being A or B compared with 22 (11%) of the 202 remaining cases (P = 0.004). Thus, either loss of bcl-2 expression or gain of abnormal p53 expression is associated with high stage and poor prognosis. The bcl-2(+)/p53(-) phenotype is similar to that of normal mucosa, and these results suggest that such cases represent an indolent group at an early stage in the progression of colorectal cancer.     

Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer.

PURPOSE: Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma which is intimately associated with EBV. The latent presence of EBV affects the function of p53, Bcl-2, and survivin. We thus investigated the relationship between EBV status, p53, Bcl-2, and survivin in biopsy specimens from patients with primary NPC. EXPERIMENTAL DESIGN: Archival formalin-fixed, paraffin-embedded NPC biopsies were evaluated in 80 patients treated with curative radiation from a single institution. The presence of EBV was determined using EBER in situ hybridization, whereas p53, Bcl-2, and survivin were assessed using immunohistochemistry. RESULTS: The majority of NPC specimens in this patient cohort were EBER-positive (64 of 78, or 82%), which in turn, was significantly associated with ethnicity (P = 0.0007), and WHO subtype 2A/2B (P = 0.04). EBER-positive tumors were also associated with p53 (P = 0.002), Bcl-2 (P = 0.04), and nuclear survivin (P = 0.03) expression. Patients with EBER-positive NPC fared better, with a 10-year overall survival of 68% versus 48% for EBER-negative patients (P = 0.03). For nuclear survivin, patients with either low or high nuclear survivin fared worse than patients with intermediate survivin expression (P = 0.05), suggesting that there is an optimal proportion of survivin-expressing cells for best function and clinical outcome. CONCLUSIONS: With an extended median follow-up time of 11.4 years, EBV status remains a strong predictor for overall survival in NPC. EBV-positive NPC has strong molecular associations with p53, Bcl-2, and survivin expression. Furthermore, we provide clinical data revealing the potentially dual nature of survivin in predicting clinical outcome.     

The prognostic relevance of apoptosis-related proteins in classical Hodgkin's lymphomas

Neoplastic cells in classical Hodgkin's lymphomas (cHL) seem to correspond to defective germinal center B-cells, which escape from apoptosis. Epstein-Barr virus (EBV) may be implicated in this protective mechanism. The aim of the present study was to determine the expression of apoptosis-related proteins in cHL among adult patients and correlate them with EBV expression, clinical findings and survival. EBV was detected by in situ hybridization (Epstein-Barr Encoded RNA, EBER, probe). Immunohistochemistry was used on paraffin sections to detect LMP-1/EBV, CD15 and the apoptosis-related proteins (bcl-2, bax, bcl-X, mcl-1 and CD95). Seventy-eight patients seen at our Institution were studied: 36 male and 42 female. Median age was 31 years (15-75 years). Histological types of cHL were: 61 nodular sclerosis (47 NS1 and 14 NS2), 15 mixed cellularity (MC), 1 lymphocyte depletion and 1 unclassified. In 50 cases there was EBV expression (64%). At least one apoptosis-associated protein was expressed in 92% and CD15 in 57.7% of the cases. In the univariate analysis, the following variables were related to a better overall survival: expression of CD15 ( p =0.023), expression of mcl-1 protein ( p =0.029), expression of bcl-2 protein ( p =0.028, only in a Cox model after stratification for histology) and expression of LMP-1 ( p =0.042). EBV expression presented a borderline inverse correlation with bcl-2. A prognostic index (PI) developed in the present study revealed that simultaneous expression of bcl-2, mcl-1 and LMP-1 was significant and independently correlated with an excellent survival.     

EBER1/2、LMP-1在NK/T细胞淋巴瘤中的表达

目的　探讨NK /T细胞淋巴瘤与EB病毒 (EBV )的关系。方法　收集 2 6例NK /T细胞淋巴瘤 (淋巴结内 10例 ,淋巴结外 16例 ) ,采用免疫组织化学S P法确定瘤细胞本质 ,用原位杂交法检测EBV编码的RNA (EBER 1/2 )。结果　①在 2 6例NK /T细胞淋巴瘤中 ,EBER1/2检出率为 46 .2 % (12 /2 6 ) ,其中淋巴结内检出率为 10 .0 % (1/10 ) ,淋巴结外检出率为 6 8.8% (11/16 ) ,2组比较有非常显著性差异 (P <0 .0 1)。②在淋巴结外NK/T细胞淋巴瘤中 ,EBER 1/2在鼻腔检出率为 90 .0 % (9/10 ) ,其它部位为 33 .3 % (2 /6 ) ,2组比较有显著性差异 (P <0 .0 5 )。③EB病毒潜伏膜蛋白 (LMP 1)在EBER1/2阳性病例中的检出率为16 .7% (2 /12 )。结论　EBV在NK /T细胞淋巴瘤的发生中有一定作用 ,并具有部位依赖性的特点 ;EBV在NK /T细胞淋巴瘤中的潜伏感染模式不完全一致。     

Molecular Grading of Oral Squamous Cell Carcinomas Infected with EBV

Background: Squamous Cell Carcinoma (SCC) is a type of cancer that is often found in oral cavity and areas ofthe head and neck. Viruses are major etiological factors through production of factors that can disturb proliferationand apoptosis regulators such as p53i, c-myc and bcl-2. This study aimed to determine the molecular grading of oralsquamous cell carcinoma (OSCCs) infected with the Epstein-Barr Virus (EBV). Methods: Twenty-seven OSCC patientsunderwent biopsy to detect EBV infection through in situ hybridization for RNA EBV (EBER) and immunohistochemicalanalysis of latent membrane protein-1 (LMP-1) and EBV nuclear antigen-1 (EBNA-1). To assess molecular grades, cellproliferation and apoptosis regulator expression i.e. inactive p53 (p53i), c-myc and bcl-2, were immunohistochemicallyanalysed. Results: The cases were divided into two groups; infected and non-infected by EBV. Regression analysisshowed that only EBNA-1 expression could affect p53i expression. Based on regression equations molecular grading ofOSCCs infected by EBV was divided into three: Grade I (low), EBNA-1 expression was 7.60, and p53i expressionwas 9.74-17.5; Grade II (medium), EBNA-1 expression was 7.61-19.7, and p53i 17.5-30.1; Grade III (high), EBNA-1expression was 19.71, and p53i ≥ 30.1. Conclusion: In OSCC infected with EBV, only EBNA-1 expression caninfluence p53i expression.     

High risk Epstein-Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma

Whether certain variants of Epstein–Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case–control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour biopsies derived from 62 patients with NPC of Hong Kong. Cluster analysis discovered five EBV subgroups 1A-C and 2A-B amongst the population carriers in contrast to the predominance of 1A and -B in the majority of NPC. Genome-wide association study (GWAS) identified a panel of NPC-associated single nucleotide polymorphisms (SNPs) and indels in the EBER locus. The most significant polymorphism, which can be found in 96.8% NPC cases and 40.1% population carriers of Hong Kong, is a four-base-deletion polymorphism downstream of EBER2 (EBER-del) from coordinates 7188–7191 (p = 1.91 × 10⁻⁷). In addition, the predicted secondary structure of EBER2 is altered with likely functional consequence in nearly all NPC cases. Using the SNPs and indels associated with NPC, genetic risk score is assigned for each EBV variant. EBV variants with high genetic risk score are found to be much more prevalent in Hong Kong Chinese than individuals of other geographic regions and in NPC than other EBV-associated cancers. We conclude that high risk EBV variants with polymorphisms in the EBER locus, designated as HKNPC-EBERvar, are strongly associated with NPC. Further investigation of the biological function and potential clinical application of these newly identified polymorphisms in NPC and other EBV-associated cancers is warranted.     

THE EXPRESSION OF APOPTOSIS RELATED GENES IN THE PROCESS OF CANCERATION OF ATYPICAL HYPERPLASIA OF MAMMARY DUCT

Objective： To investigate the expression of apoptosis related genes p53 and bcl-2 in atypical hyperplasia of mammary duct and the relationship between the gene expression and oncogenesis of breast. Methods： mRNA of apoptosis related gene p53 and bcl-2 were detected by in situ hybridization in 44 cases of atypical ductal hyperplasia. p53 protein expression was detected by immunohistochemistry. The data were compared with those of 6 cases of benign hyperplasia and 26 cases of breast carcinoma. Results： The expression of p53 mRNA was 66.7% in benign hyperplasia, 40% in atypical ductal hyperplasia （55.6% in mild, 41.7% in medium, 26.1% in severe） and 19.2% in carcinoma （of which 21.4% were intraductal carcinoma and 16.7% were invasive）. The expression of p53 protein was negative in benign hyperplasia, 24% in atypical hyperplasia （mild 11.1%, medium 25%, severe 34.8%）, 38.5% in carcinoma （intraductal carcinoma 35.7%, invasive ductal carcinoma 41.7%）. The expression of bcl-2 was negative in benign hyperplasia, 78.6% in intraductal carcinoma, 83.3% in invasive ductal carcinoma. Conclusion： Loss and mutation of p53 gene and excessive expression bcl-2 mRNA were detected in severe atypical ductal hyperplasia.     

Heterogeneity of HLA and EBER expression in Epstein-Barr virus-associated nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an aggressive tumour of multifactorial aetiology that, although rare in most parts of the world, poses a significant mortality problem in its high incidence area of Southern China. Improved therapies are an urgent requirement and, towards this end, immunotherapeutic methods are being developed in several centres. Such strategies are dependent on the immune competence of the target tumour, in particular its expression of HLA class-I. We examined HLA class-I and -II expression in 27 primary NPC biopsies and found that 15% were extensively down-regulated for class-I expression with the majority of tumour cells appearing negative. Whilst HLA class-II was expressed at high levels in the majority of tumours, 37% showed substantial down-regulation. NPC is associated with Epstein-Barr virus (EBV). Expression of the virus-encoded EBER RNAs is accepted as a marker of EBV latency and is regarded as a valuable diagnostic criterion. EBER RNAs were expressed in all samples, but in some the level was remarkably heterogeneous, being barely detectable in many tumour cells. Our study reinforces the concept of extensive phenotypic variation in NPC. There are morphological differences between tumour cells. Some tumours express HLA class-I and/or -II, whilst others are down-regulated or negative. Individual tumours may or may not express the EBV-encoded LMP-1 protein, and individual tumour cells may express high levels of EBER, yet adjacent tumour cells express very little or none.     

非霍奇金淋巴瘤组织坏死相关因素的探讨

目的 探讨非霍奇金淋巴瘤组织坏死相关因素.方法 将124例NHL分成有坏死组和无坏死组两组;分成NK/T、TCL、BcL三种类型,用IHC(SP法)标记CD95(Fas)、CD95L(FasL)、bcl-2、TNF-α;ISH技术检测EB病毒编码的小核苷酸RNA(EBER1/2);病例随访.结果 坏死组Fas、FasL、EBER1/2的表达率依次为81.5%(22/27)、74.1%(20/27)、82.5%(23/27),无坏死组依次为68.1%(66/97)、59.8%(58/97)、12.4%(12/97),与无坏死组比较P<0.005,bcl-2表达正好相反,与坏死组比较P<0.005.Fas、FasL、EBER1/2表达主要集中在NK/T和TCL,与BCL比较差异有统计学意义;而bcl-2表达主要集中在BCL,与TCL及NK/T比较差异有统计学意义.坏死组、无坏死组平均生存时间分别为7.4月、24.2月,两组比较P<0.005.结论 Fas、FasL、bcl-2的异常表迭和EBV感染,在NHL的坏死中可能发挥了一定的作用,NHL中组织坏死是多因素共同作用的结果,组织坏死与预后有关.     

171例淋巴瘤病变组织中EB病毒表达情况的分析

目的:探讨不同类型淋巴瘤与EB病毒(Epstein-Barr virus,EBV)感染的关系。方法:收集淋巴瘤组织171例,包括弥漫大B细胞淋巴瘤(DLBC)106例;结外NK/T细胞淋巴瘤,鼻型22例;霍奇金淋巴瘤(HL)19例;血管免疫母细胞性T细胞淋巴瘤(AITL)13例;黏膜相关淋巴组织B细胞淋巴瘤(MALT)11例。应用EBV Lmp-1单抗免疫组化(IHC)和生物素标记的EBER1寡核苷酸探针原位杂交(ISH)分析EBV感染与淋巴瘤的关系。结果:淋巴瘤组织中EBV Lmp-1蛋白与EBER1 mRNA总阳性率分别为11.1%(19/171)、25.7%(44/171)。其中AITL为30.8%(4/13)、61.5%(8/13);HL为47.4%(9/19)、57.9%(11/19);结外NK/T细胞淋巴瘤为22.7%(5/22)、81.8%(18/22);DLBC为0.94%(1/106)、5.7%(6/106);MALT为0(0/11)、9.1%(1/11)。结果显示EBV在DLBC及MALT中的表达率低于AITL、HL及结外NK/T细胞淋巴瘤,差异有统计学意义(P0.05);且原位杂交检测EBER1 mRNA比免疫组化检测Lmp-1蛋白更为敏感(P0.01)。结论:EBV感染与淋巴瘤有密切关系,不同类型淋巴瘤与EBV感染的关系有差异。     

Loss of p16 expression has prognostic significance in human nasopharyngeal carcinoma.

PURPOSE: p16 is an important inhibitor of cell cycle progression; absence of p16 can thus result in increased cellular proliferation. In nasopharyngeal carcinoma (NPC), absence of p16 has been reported in association with presence of the EBV and pRb. We therefore examined p16, pRb, and EBV-encoded RNA (EBER) expression in biopsy specimens from 84 patients with newly diagnosed NPC, who were treated primarily with curative radiation therapy. Our objective was to determine whether there was a correlation between these parameters and clinical outcome in NPC. EXPERIMENTAL DESIGN: Sections were cut from archival formalin-fixed, paraffin-embedded tumor blocks from NPC patients. p16 and pRb expression were determined using polyclonal and monoclonal antibodies, respectively. The presence of EBV was determined by in situ hybridization for EBER. The percentage of positively staining tumor nuclei was scored for p16 or pRb immunoreactivity. Relative intensity and proportion of cells with EBER signals were also documented. RESULTS: p16 expression was reduced (相似文献