Expression of Cyclooxygenase-2 in Nasopharyngeal Carcinoma and Its Relation to Angiogenesis and Prognosis

Objective： The purpose of this study was to evaluate cyclooxygenase-2 （COX-2） expression in nasopharyngeal carcinoma （NPC） and its correlation with clinicopathologic features, angiogenesis, and prognosis. Methods： The expressions of COX-2 and vascular endothelial growth factor （VEGF） and microvascular density （MVD） were determined with immunohistochemical methods in eighty-six NPC patients followed up over 5 years. Results： Sixty-three tumors （73.3%） were classified as COX-2 positive. COX-2 expression was positively related to VEGF expression （r=0.438, P〈0.01） and correlated with the tumor pathological grade, extent of primary lesion, lymph node metastasis, distant metastasis and shorter survival. Conclusion： Our results suggest that COX-2, being highly expressed and strongly correlated with angiogenesis in nasopharyngeal carcinoma, is apt to be used as a predictor of prognosis, including local recurrence and distant metastasis.

The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma:a retrospective study of 105 cases

Background and Objective:Nasopharyngeal carcinoma (NPC) is known for its propensity for distant metastases.Lung metastasis is one of the most important causes of death for patients with NPC.Solitary metastatic lung tumor from NPC is a distinctive group associated with a better survival.This study was to find a more effective treatment modality and prognostic factors for the group.Methods:Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively analyzed.Survival rate was calculated by the Kaplan-Meier method.The difference of survival between the patients treated by different modalities was evaluated by the log-rank test.The Cox univariate and multivariate analyses of gender, age, pathologic type, stage, adjuvant chemotherapy, evaluation of treatment for NPC, disease-free interval, size of metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis, treatment modalities, recurrent distant metastases and/or relapse of NPC were conducted.Results:The local control rate was 53.8% in chemotherapy group, 88.0% in radiotherapy +/-chemotherapy group, and 96.4% in operation +/-chemotherapy group (P<0.01).The most promising progression-free survival (PFS) and overall survival (OS) were obtained with operation +/-chemotherapy and followed by radiotherapy +/-chemotherapy.Both of them showed much better efficacy than chemotherapy (P<0.001).The Cox multivariate analysis showed that recurrent distant metastases and/or relapse of NPC affected the survival (OR=2.087, 95% CI=1.277-3.410, P=0.003).The T stage of NPC, size of metastatic tumor, hilar and/or mediastinal lymph node metastasis, and the treatment modality were independent prognostic factors.Conclusions:Operation +/-chemotherapy and radiotherapy +/-chemotherapy are better treatment of solitary metastatic lung tumor from NPC, which could improve the local control and prolong the PFS and OS.Chemotherapy is recommended for patients with higher T stage of NPC, size of metastatic tumor ≥3 cm, pulmonary hilar and/or mediastinal lymph node metastasis.

Correlation of Skp2 overexpression to prognosis of patients with nasopharyngeal carcinoma from South China

S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell -like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.

Detection of nasopharyngeal carcinoma using surface-enhanced laser desorption and ionization mass spectrometry profiles of the serum proteome

Background and Objective: Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC. Methods: A proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later. Results: Eight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples. Conclusion: SELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.

Pretreatment platelet count improves the prognostic performance of the TNM staging system and aids in planning therapeutic regimens for nasopharyngeal carcinoma:a singleinstitutional study of 2,626 patients

Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 2,626 patients with NPC were retrospectively analyzed.Platelet count >300 × 10~9/L was defined as thrombocytosis.Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy.Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival(OS)[hazard ratio(HR) = 1.810,95%confidence interval(CI) = 1.531-2.140,P < 0.001]and distant metastasis-free survival(DMFS)(HR = 1.873,95%CI = 1.475-2.379,P < 0.001) in the entire patient cohort.Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category,N category,or TNM classification(all P < 0.001).Receiver operating characteristic(ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count(P = 0.030).Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis(HR = 0.416,95%CI = 0.226-0.765,P = 0.005).Conclusions:Pretreatment platelet count,when combined with TNM classification,is a useful indicator for metastasis and survival in patients with NPC.It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

Distinct serumal proteomic patterns between ascending and descending types of loco-regionally advanced nasopharyngeal carcinoma assessed by surface enhanced laser desorption ionization and artificial neural network analyses

Nasopharyngeal carcinoma （NPC） is rare in most countries, especially in Europe and NorthAmerica （incidence rate below 1/100 000 people per year）. However, it has a high incidence in several southern areas in China, especially in the Cantonese region, including Guangzhou city, where the incidence rate is approximately 30-80/100 000 people per year. In the high incidence areas, more than 95% NPCs are poorly differentiated （WHO types 2 and 3）, which are sensitive to radiotherapy and chemotherapy. Besides its special epidemiological and pathological characteristics,

基于MRI影像组学特征因素预测II~IVa期鼻咽癌患者复发转移风险及辅助化疗受益的临床意义

目的旨在建立一个MRI影像组学和临床因素模型,以预测原发性鼻咽癌(NPC)患者复发转移的风险,并验证其对辅助化疗(adjuvant chemotherapy,AC)疗效的预测作用。方法回顾性分析2018年2月~2021年10月在深圳市龙岗区耳鼻咽喉医院诊断为II~IVa期NPC患者135例。在我院接受标准同步放化疗后,部分患者接受诱导化疗和/或基于顺铂/奈达铂的辅助化疗。利用PyRadiomics平台提取增强MRI序列的成像特征。使用最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)算法过滤与复发或转移相关的特征,在训练队列中通过Cox多变量分析构建临床影像组学模型(clinical radiomics models,CRM),并在验证队列中进行验证。根据模型的Rad评分中位数,将所有患者分为高风险组和低风险组。Kaplan-Meier生存曲线用于比较高风险组和低风险组辅助化疗患者的3年无复发转移生存期(recurrence and metastasis free survival,RMFS)。结果共提取960个成像特征。CRM由9个特征(6个影像学特征和3个临床因素)构成。在训练队列中,3年RMFS的CRM曲线下面积(AUC)为0.867(P<0.001),敏感性和特异性分别为90.32%和79.66%;在验证队列中,AUC为0.836(P<0.001),敏感性和特异性分别为100.0%和71.43%。高风险组和低风险组3年RMFS分别为42.86%(27/63)和94.44%(68/72)(Log rank=50.818,P<0.001)。在CRM高风险患者中,接受辅助化疗的患者3年RMFS明显优于未接受患者(Log rank=6.204,P=0.013)。结论基于3个临床因素和6个MRI影像学特征的CRM为预测NPC的预后结局提供一种无创的方法,可能有助于指导临床辅助化疗的治疗决策,但还需要进一步外部验证。

Commentary on: Mobley AJ, Lam YW, Lau KM, Pais VM, Lesperance JO, Steadman B, et al. Monitoring the serological Proteome Colon, the latest modality in prostate cancer detection. J Urol 2004; 172: 331-7.

This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as those with prostate cancer. In doing so, they utilize several chip platforms on which to examine the resulting

基于IMRT同步放化疗方案治疗局部晚期鼻咽癌不良预后危险因素及预测模型构建

目的探讨基于调强放疗(IMRT)同步放化疗方案治疗局部晚期鼻咽癌不良预后危险因素并构建预测模型,为临床诊疗方案优化及预后改善提供更多参考。方法收集2012年1月~2017年12月梅州市人民医院接受基于IMRT同步放化疗方案治疗局部晚期鼻咽癌患者190例,分析临床特征资料和随访生存情况,采用单因素和多因素评价患者不良预后独立危险因素;基于独立危险因素构建列线图模型并评价模型预后预测效能。结果190例患者随访过程中死亡26例,累积1年、3年及5年总生存率分别为97.4%、90.7%、87.0%。单因素分析结果显示,年龄、淋巴细胞与单核细胞绝对值比值、乳酸脱氢酶、颅底侵犯、N分级及辅助化疗情况均与局部晚期鼻咽癌不良预后有关,差异有统计学意义(P<0.05)。多因素分析结果显示,乳酸脱氢酶水平≥185 IU/L、颅底侵犯及N3均是局部晚期鼻咽癌不良预后独立危险因素(P<0.05)。将多因素分析有统计学意义指标纳入局部晚期鼻咽癌患者总生存时间列线图模型,患者总生存时间列线图模型用于累积1年、3年及5年总生存时间C-index为0.84(95%CI:0.72~0.86),总生存时间预测AUC分别为0.87(95%CI:0.75~0.93)、0.90(95%CI:0.79~0.96)、0.85(95%CI:0.80~0.98)。结论接受基于IMRT同步放化疗方案治疗局部晚期鼻咽癌患者不良预后可能与乳酸脱氢酶水平、有无颅底侵犯及N分级等密切相关,而根据上述预后因素构建线列图模型在预测患者随访总生存时间方面具有良好效能。

调强放射治疗局部晚期鼻咽癌489例远期预后影响因素及晚期安全性研究

目的探讨行调强放射治疗(IMRT)初治局部晚期鼻咽癌远期预后影响因素及晚期安全性。方法回顾性纳入2012年1月至2017年12月于梅州市人民医院行IMRT一线治疗的局部晚期鼻咽癌病人共489例,分析随访生存情况、复发转移及晚期损伤情况,采用单因素和多因素评价局部区域控制率、总生存(OS)率及无复发生存(DFS)率独立影响因素。结果489例病人随访5年局部区域控制率为92.64%(453/489),5年DFS率为84.05%(411/489),5年OS率为91.00%(445/489)。随访过程中死亡65例,其中因局部区域复发死亡25例,因远处转移死亡35例,因其他事件死亡5例。随访3~4级晚期损伤发生率为2.04%(10/489);单因素分析结果显示,临床分期与IMRT一线治疗局部晚期鼻咽癌病人5年局部区域控制率有关(P<0.05);性别、EB DNA拷贝数、临床分期及N分期均与IMRT一线治疗局部晚期鼻咽癌病人5年DFS率有关(P<0.05);年龄、EB DNA拷贝数、临床分期及N分期均与IMRT一线治疗局部晚期鼻咽癌病人5年OS率有关(P<0.05)。Cox模型多因素分析结果显示,临床分期是IMRT一线治疗局部晚期鼻咽癌病人5年局部区域控制率独立影响因素(P<0.05);性别、年龄、吸烟和EB DNA拷贝数均是IMRT一线治疗局部晚期鼻咽癌病人5年DFS率独立影响因素(P<0.05);年龄、N分期和EB DNA拷贝数均是IMRT一线治疗局部晚期鼻咽癌病人5年OS率独立影响因素(P<0.05)。结论IMRT一线治疗局部晚期鼻咽癌远期预后与多种因素有关,包括性别、年龄、EB DNA拷贝数及分期情况,而随访晚期损伤以1~2级为主。

原发性结外弥漫性大B细胞淋巴瘤的CT表现及误诊分析

目的 探讨原发性结外弥漫性大B细胞淋巴瘤的CT影像表现,总结CT误诊原因及其防范措施。方法 回顾性分析2019年1月—2021年12月收治的经手术或穿刺活检确诊为结外弥漫性大B细胞淋巴瘤8例的临床及CT影像资料。结果 8例中咽痛伴异物感和上腹部隐痛各2例,腰部隐痛、颈部肿胀并疼痛、右鼻闭塞伴右耳听力下降、低热并双下肢水肿各1例。首诊CT误诊6例,误诊为鼻咽癌、扁桃体区神经源性肿瘤、桥本甲状腺炎、脾脏转移瘤、结肠癌及胰腺癌各1例;另有2例首诊CT确诊。误诊时间1~7 d。所有患者术后病理证实均为弥漫性大B细胞淋巴瘤,给予相应治疗后均预后良好。结论 原发性结外弥漫性大B细胞淋巴瘤临床表现缺乏特异性,CT影像表现具有的共性特征对本病有重要的诊断和鉴别诊断价值,确诊需病理学检查。

305例鼻咽癌调强放疗预后因素分析

背景与目的:放疗是鼻咽癌治疗的有效手段。本研究目的是分析大样本量调强放疗(intensity-modulated radiation therapy,IMRT)治疗鼻咽癌的效果、不良反应并探索其预后因素。方法:分析从2003年9月到2006年9月在福建省肿瘤医院接受IMRT的305例鼻咽癌患者临床资料并作生存分析。肿瘤靶区的处方剂量为66～69.75Gy/30～33次。Ⅲ～Ⅳa期患者接受了以铂类为基础的化疗。结果:中位随访时间35个月(5～61个月)。分别有16、8和39例出现局部﹑颈部淋巴结复发及远处转移。3年局控率﹑区域淋巴结控制率﹑无远处转移率﹑无瘤生存率及总生存率分别为94.3%﹑97.7%﹑86.1%﹑80.3%和89.1%。多因素分析表明T分期并不影响局控率及总生存率(P>0.05),N分期是影响总生存率(P=0.000)、无远处转移率(P=0.000)及无瘤生存率(P=0.003)的独立预后因素。同步和辅助化疗不改善Ⅲ～Ⅳa期患者预后(P>0.05)。严重的急性不良反应包括Ⅲ度皮肤反应14例(4.6%)、Ⅲ度口腔黏膜反应90例(29.5%)及Ⅲ～Ⅳ度骨髓抑制20例(6.5%);IMRT治疗两年后Ⅱ度口干发生率7%,无Ⅲ～Ⅳ度口干。结论:IMRT治疗鼻咽癌可以获得较好的局部区域淋巴结控制率及总生存率,不良反应可耐受。N分期是影响预后的主要因素,为降低远处转移率进一步提高疗效还需探讨化疗的意义。

初治鼻咽癌调强放疗与常规放疗的同期对照研究

背景与目的:调强适形放疗在鼻咽癌治疗中的应用逐渐增多,取得了较好的局部控制率。本研究探讨与常规放疗比较,调强放疗能否提高鼻咽癌患者的生存率并减少放射性损伤。方法:选择2003年11月至2005年12月在福建省肿瘤医院行调强放疗的初治鼻咽癌患者190例为调强放疗组,并按1∶1配对选择同期行常规放疗的190例初治鼻咽癌患者作为对照组,两组共380例患者。随访两组的生存状况以及急性和慢性放射性损伤发生情况,对两组进行生存分析,并比较两组的疗效及放射性损伤的发生率及严重程度。结果:调强放疗组4年无局部复发生存率和局部区域控制率均高于常规放疗组(89.8%vs.80.7%,P=0.029;90.4%vs.78.3%,P=0.0107);而两组的4年无远处转移生存率、无进展生存率和总生存率差异均无统计学意义(88.6%vs.83.4%,79.4%vs.64.8%,88.9%vs.75.8%,P值均>0.05)。调强放疗患者的急性口干、颈部纤维化、张口困难的严重程度以及放疗后6个月、1、2、3、4年的口干反应均明显轻于常规放疗(P值均﹤0.05);但两组的急性黏膜反应、骨髓抑制和慢性听力损伤、放射性颅神经损伤差异均无统计学意义(P值均>0.05)。结论:调强放疗可提高初治鼻咽癌患者的无局部复发生存率及局部区域控制率,并能减轻患者的部分急慢性放射性损伤,但未能提高总生存率。

治疗前体重指数对鼻咽癌患者预后的影响

背景与目的:肥胖和低体重与多种肿瘤的进展及预后相关。本研究探讨体重指数(body mass index,BMI)对鼻咽癌患者预后的影响,为判断鼻咽癌患者的预后提供参考。方法:从1990-2003年在中山大学肿瘤防治中心确诊为鼻咽癌的病例中随机抽取1489例,按照患者的BMI分为正常、低体重、超重和肥胖4组。采用生存分析对4组患者的预后进行综合比较分析。结果:低体重组、超重组和肥胖组患者的年龄、T分期、N分期和总分期与正常体重组相比其差异均有统计学意义(P<0.0001)。以低体重组为对照组,正常组、超重组和肥胖组的总生存率、无复发生存率和无转移生存率的相对危险度均小于1,并且随着体重的增加相对危险度逐渐降低。单因素生存分析结果显示,低体重组总生存率、无复发生存率和无转移生存率低于正常体重组和超重组、肥胖组(P<0.0001);多因素分析结果表显示,年龄、T分期、N分期和BMI分级均可作为显著的独立预后因素(P<0.05)。结论:治疗前低BMI鼻咽癌患者的总生存率、无复发生存率、无转移生存率较正常BMI患者下降。治疗前BMI可作为评价鼻咽癌患者预后的一个重要参考指标。

诱导化疗联合同期放化疗与同期放化疗治疗局部晚期鼻咽癌的对比研究

目的:比较诱导化疗联合同期放化疗与同期放化疗治疗局部晚期鼻咽癌(LA-NPC)的临床结果及探讨预后因素。方法:分析2005年1月至2006年12月本院收治的433例无转移LA-NPC患者的临床资料,按是否行诱导化疗分为诱导化疗联合同期放化疗组(A组)209例与同期放化疗组(B组)224例。采用Kaplan-Meier法进行生存分析,差异比较采用Log-Rank法双侧检验,预后因素分析采用Cox模型。结果:A组、B组的3年总生存率(OS)、无局部区域复发生存率(LR-FFS)、无远处转移生存率(D-FFS)、无瘤生存率(FFS)分别为87%vs.88%、95%vs.95%、85%vs.85%、81%vs.81%;A组、B组的5年OS、LR-FFS、D-FFS、FFS分别为80%vs.82%(P=0.503),95%vs.93%(P=0.673),82%vs.82%(P=0.992),78%vs.77%(P=0.851)。两组生存差异无统计学意义,对于Ⅲ期鼻咽癌,A组FFS优于B组(P=0.075)。多因素分析显示老年、临床分期晚、颅神经侵犯、贫血、N分期晚为OS、D-FFS的独立不良预后因素。结论:与同期放化疗相比,诱导化疗联合同期放化疗未提高LA-NPC的OS、LR-FFS、D-FFS及FFS,但具有改善Ⅲ期鼻咽癌FFS的趋势。诱导化疗联合同期放化疗不是鼻咽癌的必选治疗模式。

313例老年鼻咽癌患者临床特征及预后的回顾性研究

背景与目的:鼻咽癌大样本、前瞻性的随机临床研究及回顾性临床分析很多,但绝大多数研究中老年患者被排除在外。本文通过回顾性研究老年鼻咽癌的临床特征和预后因素,探讨其临床特点并提高对老年鼻咽癌的认识。方法:收集313例1998年1月1日～2001年12月31日在中山大学肿瘤防治中心鼻咽癌科初次住院、年龄≥60岁的老年鼻咽癌患者的临床资料进行分析,其中男性265例,女性48例。放疗295例,其中91例加化疗,无治疗和单纯化疗共18例。采用Kaplan-Meier法进行生存分析,log-rank检验各组生存率。采用Cox回归模型进行预后多因素分析。结果:接受放疗的295例老年鼻咽癌患者1、3、5年总生存率分别为77%、58%、48%,1、3、5年肿瘤相关生存率分别为78%、60%、53%。单因素分析显示P92分期、T分期、N分期、颅底骨受侵、颅神经损伤、原发灶剂量、照射野、放疗天数对预后有影响(P<0.05)。Cox回归模型显示仅092分期是独立的预后影响因素(β=0.509,P<0.01),而化疗不是对老年鼻咽癌患者预后有利的影响因素(β=0.649,P=0.42)。结论:放疗是老年鼻咽癌患者治疗的主要手段,化疗未能明显改善老年鼻咽癌患者的预后;092分期能够较好地预测老年鼻咽癌的预后;老年鼻咽癌患者的预后比非老年患者差。

鼻咽癌p53 p21^(WAF1)和MDM2蛋白异常表达的临床意义

目的:探讨p53、p21WAF1、MDM2蛋白在原发鼻咽癌(NPC)异常表达的临床意义。方法:采用LSAB法检测69例原发NPC组织中p53、p21WAF1和MDM2蛋白的表达状况。结果:1)p53、p21WAF1和MDM2蛋白在原发NPC组织的阳性表达率分别为79.7%、84.1%、和82.6%;高表达率分别为50.7%、46.4%和31.9%。2)p53蛋白的高表达率随TNM分期的升高而增多,P=0.042。3)p53或MDM2蛋白高表达者的复发间期显著短于相应蛋白低表达/阴性者,分别P=0.038和P=0.002。4)p53和MDM2蛋白同时高表达者、MDM2蛋白高表达同时p21WAF1蛋白低表达/阴性者的复发间期明显短于对照组,分别P<0.001;p21WAF1蛋白高表达同时p53蛋白低表达/阴性者、p53和MDM2蛋白同时低表达/阴性者的复发间期显著长于对照组,分别P=0.002和P=0.014。5)p53和MDM2蛋白高表达同时p21WAF1蛋白低表达/阴性者的复发间期明显短于对照组,P<0.001;p53和MDM2蛋白低表达阴性同时p21WAF1蛋白高表达者的复发间期明显长于对照组,P=0.002。结论:p53或MDM2蛋白高表达提示有促进NPC复发的作用,p21WAF1蛋白高表达提示有抑制NPC复发的作用。单独检测p53或MDM2蛋白在原发NPC组织的表达情况可以作为预测NPC复发倾向和临床预后的参考指标;如同时检测p53、MDM2和p21WAF1蛋白的两项或三项指标,预测意义更理想。

表皮生长因子受体活化与鼻咽癌患者无转移生存的关系

背景与目的:表皮生长因子受体(epidermal growth factor receptor,EGFR)在多种肿瘤中高表达,且与预后相关,然而,EGFR对鼻咽癌的预后价值尚存争议。本研究检测鼻咽癌组织中EGFR及其磷酸化形式(phosphorylated EGFR,pEGFR)的表达,探讨其与鼻咽癌预后的关系。方法:收集中山大学肿瘤防治中心1999年1月至12月住院治疗鼻咽癌患者的鼻咽癌组织110例,同时收集20例正常鼻咽组织。利用免疫组化方法检测鼻咽癌组织及正常鼻咽组织中EGFR及pEGFR的表达,半定量方法评价染色情况;采用单因素和多因素方法分析蛋白表达与临床病理特征及预后的关系。结果:EGFR及pEGFR在鼻咽癌组织和鼻咽正常组织的阳性率分别为100%(110/110)、10%(2/20)和60%(66/110)、15%(3/20),不同组织中两种蛋白表达的差异均具有统计学意义(P<0.001);EGFR蛋白高表达与T分期相关(P=0.034),而与其他临床病理特征无关。单因素分析显示pEGFR高表达患者5年无转移生存率显著低于pEGFR低表达患者(72.2%vs.91.0%,P=0.012),而多因素分析显示pEGFR表达不是鼻咽癌患者无转移生存的独立预后因素。结论:pEGFR高表达与鼻咽癌患者的无转移生存相关,EGFR活化可能与鼻咽癌的转移有关。

初治鼻咽癌调强适形放疗近期临床观察

目的 研究调强放射治疗（IMRT）对初治鼻咽癌的疗效以及对正常组织的保护和毒性反应。方法 对24例鼻咽癌初治患者鼻咽和全颈及锁骨上全程实施IMRT，肿瘤靶区授予处方剂量68～70Gy。对于Ⅲ和Ⅳ期患者，在IMRT同时，结合患者淋巴结转移及一般情况给予PDD＋5-Fu±THP-ADM方案化疗1～2周期。结果 治疗计划结果显示，覆盖鼻咽GTV1D95的平均剂量为70．48Gy，GTvlV95的平均体积为98．46％；靶区内GTV1、GTV2、CTV1和CTV2的平均剂量分别为70．48Gy、66．98Gy、60．10Gy和51．18Gy。本组有2例、16例、5例和1例患者分别出现0、1、2和3级的皮肤急性放射性反应；有4例、6例、13例和1例患者分别出现1、2、3和4级的口腔粘膜急性放射性反应；其中1例合并联合化疗患者因严重口腔粘膜炎中断放疗1周。其他合并化疗患者在化疗后均出现不同程度的骨髓抑制，经对症处理均未影响正常放射治疗。本组患者中位随访期13个月。无1例出现局部复发或远处转移。结论 IMRT在初治早期或晚期鼻咽癌病例均可获得理想的剂量分布，正常组织得到很好的保护，毒副反应可以耐受，临床疗效令人满意。

Wnt-1、β-catenin在鼻咽癌组织中的表达及其临床意义

背景与目的:Wnt-1和β-catenin分别作为Wnt/β-catenin信号通路中的信号分子及关键分子在多种肿瘤中异常表达,且与预后不良有关。本研究通过检测Wnt-1、β-catenin在鼻咽癌组织中的表达,探讨其与鼻咽癌临床预后的关系。方法:用免疫组化SP法检测111例鼻咽癌组织中Wnt-1、β-catenin蛋白的表达情况,分析其与鼻咽癌无复发生存率、无转移生存率和无进展生存率的关系。结果:111例标本中,β-catenin高表达64例(57.7%),晚期鼻咽癌β-catenin的高表达率高于早期(63.1%vs40.7%,P=0.041);β-catenin高表达组的无复发生存率、无转移生存率、无进展生存率均显著低于低表达组(P<0.05)。多因素Cox回归模型显示β-catenin高表达与肿瘤进展有关。Wnt-1高表达68例(61.3%),高表达组与低表达组的无复发生存率、无转移生存率、无进展生存率相比,两者差异无统计学意义(P>0.05)。结论:部分鼻咽癌中可能存在Wnt/β-catenin通路的异常活化,β-catenin可作为鼻咽癌的一个预后指标。