口腔、颌面

口腔鳞癌组织中survivin蛋白的表达及与血管生成的关系；颏下岛状皮瓣修复口腔颌面部肿瘤术后缺损的临床研究；口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2的表达及临床意义；晚期上颌窦鳞癌组织中GST-π和PCNA的表达与预后的关系；舌体鳞癌颈淋巴结阴性患者的颌部治疗策略；腮腺多形腺瘤手术方式的选择。     

非小细胞肺癌组织GST-π表达及其临床意义的研究

目的:检测谷胱甘肽S-转移酶(GST-π)在非小细胞肺癌(non-small cell lung cancer, NSCLC)中的表达,分析其与预后的关系.方法:将109例NSCLC患者的手术标本及11例正常肺组织标本制成组织芯片,采用SP免疫组化方法检测GST-π的表达,并与病理特征及生存时间进行分析.结果:109例NSCLC患者中,GST-π表达阳性为68例(62.4%),正常肺组织为1例(9.1%),差异有统计学意义,x2=9.535,P=0.002.GST-π的表达与年龄、分化程度、TNM分期及淋巴结转移无关,P均>0.05,但与性别,病理类型和吸烟有关,x2值分别为0.749、3.879和4.898,P值分别为0.005、0.049和0.027.Cox多因素分析显示,TNM分期是影响预后的独立危险因素(95%CI:1.625～3.893),P=0.000,GST-π的表达与生存期无关,P=0.940.结论:GST-π的表达可能与预后无关.     

ToPoll、MRP、GST-π在胃癌组织中的表达及其与预后的关系

[目的]探讨多药耐药基因相关蛋白在胃癌组织中的表达及其与预后的关系.[方法]免疫组化方法检测109例胃癌组织中ToPoⅡ,MRP,GST-π的表达,并分析他们与胃癌临床病理特征和预后间的关系.[结果]109例胃癌组织中,ToPo Ⅱ,MRP,GST-π阳性率分别为74.3%,40.4%和48.6%.3种蛋白各自表达的阳性组与阴性组比较,1、3、5年生存率均无统计学差异.高危组(2个以上危险因素)1、3、5年生存率分别为85.1%,57.4%,46.8%;低危组(1个危险因素)1,3,5年生存率分别为85.5%、64.5%、61.3%,但差异无统计学意义(X2=0.15,p=0.926).[结论]ToPo Ⅱ,MRP,GST-π与胃癌临床病理特征相关,3种耐药蛋白的联合检测可能成为预测胃癌患者预后的指标.     

TopoⅡα、GST-π、P-gp对卵巢癌患者化疗反应及预后预测的体内外实验

目的研究TopoⅡα、GST-π、P-gp在卵巢癌耐药中的作用及其对化疗反应及预后的预测价值。方法免疫组织化学SP法检测TopoⅡα、GST-π、MDR-1/P-gp在80例上皮性卵巢癌组织中的表达,分析它们与化疗反应及预后的关系;RNA干扰封闭GST-π、MDR-1/P-gp在人卵巢癌耐药细胞中的表达,检测其逆转细胞耐药的可能性。结果 TopoⅡα阴性和阳性患者的化疗反应无差异。GST-π阴性患者的化疗疗效显著优于阳性者(P=0.009);P-gp阴性患者也较阳性者疗效好,但差异无统计学意义(P=0.059)。尽管Log-rank test显示GST-π或P-gp阴性患者的生存时间显著长于相应指标阳性患者,但Cox分析并未指示两者为独立预后因素(P=0.682;P=0.101)。根据GST-π、P-gp的共同表达情况进一步分组分析显示,两者共同阴性的患者化疗有效率100%、85.7%生存至末次随访,GST-π、P-gp共同阴性预示较好的化疗反应及预后(P=0.012;P=0.000)。体外实验显示,卵巢癌耐药细胞对多种化疗药物敏感度降低,同时GST-π、MDR-1/P-gp mRNA表达增高。结论 GST-π及MDR-1/P-gp在卵巢癌耐药中具重要作用,GST-π或P-gp单独预测化疗反应及预后的效用有限,联合检测可提供较高临床价值,封闭两者表达可一定程度逆转卵巢癌细胞的耐药性。     

ToPoⅡ、MRP、GST-π在胃癌组织中的表达及其与预后的关系

[目的]探讨多药耐药基因相关蛋白在胃癌组织中的表达及其与预后的关系。[方法]免疫组化方法检测109例胃癌组织中ToPoⅡ、MRP、GST-π的表达,并分析他们与胃癌临床病理特征和预后间的关系。[结果]109例胃癌组织中,ToPoⅡ、MRP、GST-π阳性率分别为74.3%、40.4%和48.6%。3种蛋白各自表达的阳性组与阴性组比较,1、3、5年生存率均无统计学差异。高危组（2个以上危险因素）1、3、5年生存率分别为85.1%、57.4%、46.8%;低危组（1个危险因素）1、3、5年生存率分别为85.5%、64.5%、61.3%,但差异无统计学意义（χ2=0.15,P=0.926）。[结论]ToPoⅡ、MRP、GST-π与胃癌临床病理特征相关,3种耐药蛋白的联合检测可能成为预测胃癌患者预后的指标。     

食管鳞癌组织GST-π和TOPO-Ⅱ表达及其相关性研究

目的:研究食管鳞癌组织谷胱甘肽S-转移酶-π(GST-π)和DNA拓扑异构酶Ⅱ(TOPO-Ⅱ)表达及其相关性研究.方法:应用免疫组化SP法检测GST-π和TOPO-Ⅱ48例食管鳞癌组织和30例正常黏膜组织中的表达.结果:在正常食管黏膜和食管鳞癌组织中GST-π和TOPO-Ⅱ的阳性表达率分别为30.00%(9/30)、20.00%(6/30)和64.58%(31/48)、41.67%(20/48);食管鳞癌组织和正常食管黏膜比较差异均有统计学意义,P＜0.05.GST-π和TOPO-Ⅱ的表达与淋巴结转移无关;与分化程度有关;GST-丌与TOPO-Ⅱ的表达呈负相关(r=-0.787,P＜0.05).结论:联合检测GST-π和TOPO-Ⅱ可以作为判断食管癌浸润、转移能力的有效指标.同时可应用于预测患者临床化疗的敏感性,筛选出不具有耐药的联合方案,提高疗效.     

卵巢癌GST-π基因的表达及其临床意义

目的探讨谷胱甘肽-S-转移酶(GST-π)基因在卵巢癌组织中的表达及其与临床病理特征之间的关系.方法应用免疫组化SP法对30例卵巢癌,30例卵巢良性肿瘤和20例正常卵巢组织中的GST-π基因的表达进行研究.结果在卵巢癌和卵巢良性肿瘤组织中GST-π蛋白表达的阳性率分别为56.7%和13.3%,正常卵巢组织中无GST-π蛋白的表达,差异均有显著性(P＜0.05);GST-表达的阳性率在卵巢癌病理1～2级组明显高于3级组,差异有显著性(P＜0.05).GST-π蛋白表达与卵巢癌临床分期和淋巴结转移无明显的相关性.结论GST-π基因的改变与卵巢癌的发生有关,GST-π蛋白表达可作为临床诊断卵巢恶性肿瘤的辅助指标.     

基于GEO数据库的胃癌耐药基因表达谱分析及其对预后的影响

目的通过对相关数据库数据分析,探讨胃癌组织耐药基因表达与患者生存和预后的关系。方法对NCBI中GEO数据库中的数据集数据进行表达量分析、生存分析和相关性分析。结果 (1)研究分析表明,ABCB1、LRP、GCS和GST-π基因在胃癌组织中存在明显的高表达(ABCB1,P<0.0001;LRP,P<0.0001;GCS,P=0.0035;GST-π,P<0.0001)。(2)在胃癌组织中ABCB1与LRP及GCS与GST-π的表达均呈正相关(P<0.0001,γ=0.6666);而ABCB1与GCS的表达呈负相关(P=0.032,γ=-0.02301)。(3)ABCB1与GCS的高表达会导致胃癌患者的总生存率和无复发生存率明显降低。结论通过分析表明,在胃癌中部分相关耐药基因的存在差异表达,这些差异表达的基因之间存在相关性,而且对患者的生存及预后又具有重要影响。     

P-gp、GST-π、Topo-Ⅱ在宫颈癌组织中的表达及意义

目的探讨P-糖蛋白（P-gp）、谷胱甘肽S-转移酶-π（GST-π）和DNA拓扑异构酶Ⅱ（TopoⅡ）在宫颈癌组织中的表达及其临床意义。方法采用免疫组化方法检测20例正常宫颈、30例宫颈上皮内瘤变（CIN）、60例初治宫颈癌及10例复发宫颈癌组织中P-gp、GST-π、TopoⅡ的表达，分析P-gp、GST-π、Topo-Ⅱ的表达与宫颈癌患者临床病理特征及3年生存率之间的关系。结果 ①P-gp、GST-π、Topo-Ⅱ在正常宫颈、CIN、初治宫颈癌及复发宫颈癌组织中均有表达，表达强弱顺序依次为：复发宫颈癌〉初治宫颈癌〉CIN〉正常宫颈。②宫颈癌组织中存在3种耐药蛋白的共表达，P-gp与、GST-π、Topo-Ⅱ的表达呈正相关（P〈0．05）；GST-π与Topo-Ⅱ的表达无显著性相关（P〉0．05）。P-gp、GST-π与初治宫颈癌临床分期，组织学类型和病理分级无关（P〉0．05）；TopoⅡ在宫颈腺癌中的表达水平明显低于鳞癌（P〈0．05）。④P-gp、GST-π、Topo-Ⅱ低表达者3年生存率优于高表达者，差别有统计学意义（P〈0，05）；TopoII低表达者与高表达者3年生存率差别无统计学意义（P〉0．05）。结论P-gp、GST-π、Topo-Ⅱ可能与宫颈癌的发生发展相关。P-gp、GST-π、Topo-Ⅱ表达强度的增加不仅可为宫颈癌化疗用药提供参考，而且可作为宫颈癌判断预后的指标。     

151例上颌窦恶性肿瘤的预后因素分析

背景与目的:上颌窦恶性肿瘤患者的5年生存率较低,影响其预后的因素尚未研究清楚,有关这方面的研究报道不多,本研究旨在探讨影响上颌窦恶性肿瘤预后的临床病理因素.方法:回顾性分析1983年9月~1999年3月中山大学肿瘤防治中心收治的151例初治上颌窦恶性肿瘤病例,包括鳞癌72例,腺癌44例,肉瘤16例,其它病理类型19例;按UICC1997年分期:Ⅱ期7例,Ⅲ期55例,Ⅳ期89例;手术联合放疗66例,单纯手术14例,单纯放疗25例,其它治疗方式者39例,7例放弃治疗本研究所有病例均随访5年以上.统计用SPS10.0软件包完成,用Kaplan-Meier 法分析临床、病理参数等各单因素对上颌窦恶性肿瘤预后的影响;用Cox模型进行多因素分析.结果:(1)年龄≤40岁和年龄＞40岁的5年累积生存率分别为55.7%和33.3%(P=0.030).(2)鳞癌、腺癌、肉瘤及其它类型患者的5年累积生存率分别为30.2%、57.5%、24.3%和50.7%(P=0.011).(3)Ⅱ、Ⅲ、Ⅳ期患者的5年累积生存率分别为85.7%、45.8%和32.7%(P=0.029).(4)有无淋巴结转移患者的5年累积生存率分别为14.4%和44.1%(P=0.005).(5)有无远处转移患者的5年累积生存率分别为14.3%和41.1%(P=0.011).(6)未治、单纯手术、单纯放疗手术联合放疗和其它治疗方式的5年累积生存率分别为14.3%、42.9%、32.3%、50.8%和29.1%(P=0.004).(7)单因素分析表明以上6个因素是上颌窦恶性肿瘤预后的影响因素;多因素分析显示手术联合放疗(P=0.004,OR＜1)、临床分期(P=0.025,OR＞1)、鳞癌(P=0.016,OR＞1)、肉瘤(P=0.025,OR＞1)是影响上颌窦恶性肿瘤预后的独立因素.结论:上颌窦恶性肿瘤患者,鳞癌、肉瘤较腺癌及其它病理类型的预后差,肉瘤的预后较鳞癌差;临床分期越晚者预后越差;手术联合放疗为最佳治疗方式.     

VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell carcinoma in relation to p53 status, spontaneous apoptosis and prognosis

We have previously reported that p53 mutations, loss of bax expression or decreased spontaneous tumor apoptosis were associated with poorer prognoses in maxillary sinus squamous cell carcinoma (SCC)(Cancer 94: 1968-1980, 2002). In the present study, we analyzed tumor angiogenesis monitored by expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and tumor microvessel density, in correlation with p53 status, spontaneous apoptosis or disease prognosis in the same group of 70 maxillary sinus SCC patients. Tumor biopsy specimens obtained prior to initiation of treatment were examined for expression of VEGF and bFGF and tumor microvessel density using immunohistological methods. Average vessel density (AVD) (range: 3-75; median: 25) and maximum vessel density (MVD) (range: 4-125; median: 53) were assessed by the number of microvessels stained with anti-CD31 mAb in tumor lesions. VEGF was expressed in 35 (50%) of 70 patients and bFGF was in 43 (61%). Patients with VEGF expression showed significantly higher levels of MVD than those without VEGF expression (57 vs. 38; P=0.019). The VEGF expression was observed more frequently in patients with p53 overexpression and/or mutation than in those with normal p53 status (P=0.048). The MVD inversely correlated with the apoptotic index (AI) defined as the number of single stranded (ss)-DNA-positive cells per 1000 tumor cells (r= -0.23; P=0.022). Patients with neck lymph node and/or distant metastases after surgery showed significantly higher levels of MVD than patients without any metastasis (64 vs. 42; P=0.048). Low histological effectiveness of radiochemotherapy correlated with bFGF expression (P=0.0059). To clarify actual prognostic factors for maxillary sinus SCC, we selected 57 patients treated uniformly with preoperative radiochemotherapy followed by maxillectomy. Kaplan-Meier analysis showed that survival was significantly worse in patients with high MVD (> or =80) than in those with low MVD (<80) (P=0.042). These data suggest that the VEGF expression in association with the p53 overexpression and/or mutations may cause increased microvascularity, decreased spontaneous apoptosis or metastases, while the bFGF expression may be associated with resistance to radiochemotherapy, thereby resulting in poorer prognoses in maxillary sinus SCC. VEGF and bFGF expression and tumor microvessel density in tumor lesions were analyzed in 70 patients with maxillary sinus squamous cell carcinoma. The VEGF expression dependent of p53 overexpression and/or mutations was associated with angiogenesis, decreased spontaneous tumor apoptosis and metastases, while the bFGF expression was associated with resistance to radiochemotherapy, resulting in poor prognosis.     

Association of tapasin and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma lesions with reduced survival of patients.

PURPOSE: The purpose of this research was to assess the frequency and clinical significance of antigen processing machinery component and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma (SCC) lesions. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor biopsy specimens at pretreatment status from 70 Japanese patients with maxillary sinus SCC were examined for HLA class I antigen and endoplasmic reticulum chaperone molecule expression using an immunohistochemical method. Furthermore, the results of immunohistochemical staining of the lesions were correlated with their histopathological characteristics and with the clinical course of the disease. RESULTS: Calnexin, ERp57, calreticulin, tapasin, and HLA class I antigens were down-regulated in 13, 13, 24, 69, and 78% of the 70 lesions tested, respectively. Both tapasin and HLA class I antigen expression were significantly correlated with the number of infiltrating CD3(+) T cells into tumor lesions (P < 0.01); furthermore, tapasin expression was significantly correlated with tumor differentiation (P = 0.024). Tapasin expression was correlated with that of HLA class I antigens (P < 0.01). Furthermore, tapasin and HLA class I antigen down-regulation in SCC lesions was significantly associated with reduced survival of patients (P = 0.01 and P = 0.002, respectively). Multivariate Cox proportional hazards model analysis identified HLA class I antigen down-regulation as an independent prognostic marker. CONCLUSIONS: Tapasin expression appears to be associated with HLA class I antigen expression in primary maxillary sinus SCC lesions. Furthermore, defects in tapasin and HLA class I antigen expression in primary maxillary sinus SCC lesions may play a role in the clinical course of the disease, because these defects were associated with poor prognosis.     

上颌窦恶性肿瘤组织中p53和PCNA的表达及其意义

背景与目的：据文献报道,p53和增殖细胞核抗原（proliferating cell nuclear antigen,PCNA)与恶性肿瘤的发生发展有密切关系,本研究检测p53和PCNA在上颌窦恶性肿瘤、良性肿瘤和炎症性病变中表达的强度差异,探讨p53和PCNA与上颌窦恶性肿瘤临床分期、病理分型及淋巴结转移的关系。方法：用免疫组化的方法检测108例上颌窦恶性肿瘤、19例上颌窦良性肿瘤、8例鼻粘膜炎症中p53与PCNA的表达情况。数据统计采用秩和检验,并用平均秩衡量p53和PCNA的阳性表达强度。结果：在上颌窦良性肿瘤和鼻粘膜炎症两组中,p53和PCNA的平均秩分别为42．8、50．3和47．9、46．8;在恶性肿瘤组中,p53和PCNA平均秩分别高达73．0和73．2;在上颌窦恶性肿瘤中,鳞癌p53的平均秩为60．7,比腺癌的平均秩（43．9）高,有显著性差异（P＜0．05）。但临床分期I－Ⅳ期中,p53平均秩分别为46．6、50．1、56．1、55．0,PCNA平均秩分别为60．5、48．8、56．1、53．9;在无淋巴结转移组和有淋巴结转移组中,p53平均秩分别为53．7和57．3,PCNA平均秩分别为53．9和56．4;在生存期＜3年、＜5年和≥5年等3组中,p53平均秩分别为49．9、53．7和48．5,PCNA平均秩分别为45．7、56．9和52．0,均无显著性差异（P＞0．05）。结论：p53和PCNA与上颌窦恶性肿瘤尤其是鳞癌的发生、发展有一定相关性,而与上颌窦恶性肿瘤的临床分型、淋巴结转移和预后无关。     

增殖细胞核抗原表达与卵巢浆液性乳头状囊腺癌预后的关系

目的　探讨增殖细胞核抗原 (PCNA)在卵巢浆液性乳头状囊腺癌 (卵巢浆乳癌 )的表达及其与肿瘤生物学行为及预后的关系。方法　用单克隆抗体PC10免疫组化 (LSBA)染色石蜡包埋的卵巢组织。结果　PCNA在卵巢良性浆液性肿瘤及恶性肿瘤中均有表达 ,但浆乳癌中PCNA的阳性表达率 (73% )明显高于良性及交界性卵巢肿瘤 (7% ,2 7% ,P <0 .0 5 )。卵巢浆乳癌中PCNA阳性表达率随临床期别的升高而升高 ,中晚期 (Ⅱ～Ⅲ期 )卵巢癌PCNA阳性表达率明显高于早期患者 (P <0 .0 5 )。单因素及多因素生存分析显示 ,PCNA表达与否是卵巢浆乳癌一个相对独立的预后指标 (P <0 .0 0 1)。结论　PCNA的阳性表达与卵巢浆乳癌的不良预后有关。     

Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

BACKGROUND: Many researchers have attempted to correlate p53 mutation and spontaneous apoptosis with the effectiveness of radiochemotherapy and with prognosis in several malignancies. METHODS: The current study group consisted of 70 Japanese patients with maxillary sinus squamous cell carcinoma (SCC). Fifty seven patients were treated with radiochemotherapy followed by total or partial maxillectomy, and the remaining 13 patients were treated with radiotherapy alone. Tumor biopsy specimens at pretreatment status were examined for apoptosis-related proteins such as p53 protein, Fas, bax, bcl-x, and apoptosis using immunohistologic methods. The proportion of apoptotic cells labeled by single stranded DNA antibody was expressed as an apoptotic index (AI). p53 mutations at exons 5 through 8 were analyzed by direct sequence on polymerase chain reaction amplified products obtained from laser microdissected tissues. The effectiveness of radiochemotherapy was investigated histologically on surgically dissected specimens. RESULTS: p53 mutations were identified in 20 (29%) of 70 patients. p53 protein was overexpressed in 39 patients (56%), Fas in 20 patients (29%), bax in 40 patients (57%), and bcl-x in 33 patients (47%). Overexpression of bax was associated with negativity of bcl-x (P = 0.015) and with high AI (P = 0.024). Low AI and/or p53 mutation in the pretreatment tissues correlated with low histologic effectiveness of radiochemotherapy (P = 0.048, P = 0.019, respectively). Kaplan-Meier analysis as well as univariate analysis using the Cox proportional hazards model showed that low histologic effectiveness of radiochemotherapy (P = 0.0281, P = 0.0284, respectively), p53 mutations (P = 0.0095, P = 0.0187, respectively), negativity of bax (P = 0.0069, P = 0.0191, respectively), and low AI (P = 0.0134, P = 0.0407, respectively) were significantly related to worse disease-free survival. Multivariate analysis showed AI as an independent factor predicting for disease-free survival (P = 0.0455). CONCLUSIONS: The p53 mutations, expression of bax, and levels of spontaneous apoptosis have prognostic value in maxillary sinus SCC; AI especially is an independent factor for disease-free survival. A high level of spontaneous apoptosis induced by overexpression of bax may increase sensitivity of radiochemotherapy resulting in good prognosis, while p53 mutation may lead to resistance against radiochemotherapy, resulting in poor prognosis.     

Preoperative chemotherapy and radiation therapy for squamous cell carcinoma of the maxillary sinus

OBJECTIVE: This study was undertaken to assess the prognostic factors for the management of squamous cell carcinoma (SCC) of the maxillary sinus, who received preoperative chemotherapy and radiation therapy (RT). We also elucidated the appropriate sequence of chemotherapy. METHODS: A total of 124 patients (median age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3 or T4 disease was found in 93% of the patients. Thirty-nine patients received neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60 Gy. Maxillectomy was undertaken in 98 patients. RESULTS: The 5 year overall survival (OAS) and local control probability (LCP) were 56.6 and 73.7%, respectively. On univariate analysis, surgery (P < 0.0001) and T classification (P < 0.04) were significant prognostic factors for OAS and LCP. Histological grade and nodal status were also related to OAS. However, any chemotherapy sequence was not associated with the treatment outcome. On multivariate analysis, surgery (P < 0.0005) and T classification (P < 0.05) were identified as significant prognostic factors for LCP and OAS. CONCLUSIONS: This study suggests that both surgery and T stage are important prognostic factors for LCP and OAS in the management of SCC of the maxillary sinus. The appropriate sequence of chemotherapy remains to be elucidated in the future study.     

Prognostic significance of cyclin E overexpression in laryngeal squamous cell carcinomas.

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of cells. However, the clinical significance of cyclin E in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. We examined the expression of cyclin E in 102 patients with LSCC and analyzed its relation to clinicopathological parameters, cell proliferation, and clinical outcome. Cyclin E overexpression was observed in 54 cases (52.94%) of LSCC and was significantly correlated with the tumor site (P = 0.012), tumor size (P = 0.006), poor differentiation (P = 0.026), lymph node metastasis (P = 0.012), and advanced stage (P = 0.002). A positive correlation between the cyclin E expression and proliferative activity of tumor cells was found (r = 0.896; P < 0.0001). Kaplan-Meier analysis showed that shorter disease-free and overall survival was significantly associated with proliferating cell nuclear antigen (PCNA) overexpression and cyclin E overexpression. When PCNA and cyclin E are combined, the patients with both PCNA overexpression and cyclin E overexpression had the poorest prognoses when compared with the other cases. Additionally, in early stage (I-II) cases, cyclin E was also revealed to possess a significant prognostic role. By multivariate analysis, lymph node metastasis and cyclin E overexpression were independent prognostic factors for disease-free survival, and tumor size, lymph node metastasis, advanced stage, as well as cyclin E overexpression were independent prognostic factors for overall survival. These findings indicate that cyclin E overexpression is associated with unfavorable clinicopathological parameters and represents an independent marker for cell proliferation and prognosis of LSCC.     

p53、c-erbB2基因、增殖细胞核抗原表达与卵巢上皮性癌预后的关系

背景与目的：p53、c-erbB2基因和增殖细胞核抗原（proliferating cell nuclear antigen,PCNA)的表达与卵巢癌预后关系问题已有报道,由于研究方法、样本大小等方面的不同,结果存在差异。为进一步探讨p53、c-erbB2基因和PCNA表达与卵巢上皮性癌预后的关系,我们进行了本研究。材料与方法：1990年3月1日至1994年3月31日间确诊的卵巢上皮性癌共84例,采用标记的链白素－生物素辣根过氧化酶复合物（LSAB）免疫组化方法检测癌组织中p53、c-erbB2基因和PCNA的表达,使用SPSS8．0版分析它们的表达与卵巢癌患者平均生存期、5年生存率之间的关系。结果：本组84例癌组织中,p53、c-erbB2和PCNA表达的阳性率分别为58．3％（49／84）、77．5％（65／84）和100％（84／84）。单因素分析显示,c-erbB2过度表达和PCNA表达强度与患者的平均生存期、5年生存率均呈负相关（P值分别为0．05和小于0．01）,未发现p53蛋白表达与患者的平均生存期、5年生存率之间存在相关性（P＞0．05）。多因素分析发现卵巢上皮性癌的预后与临床分期、组织分化程度有关,而与p53、c-erbB2和PCNA的表达均无相关性。结论：p53的表达与卵巢上皮性癌的预后无关,而c-erbB2、PCNA表达对卵巢上皮性癌预后的影响是间接的。临床分期、组织分化程度仍是卵巢上皮性癌独立的预后因素。     

E-cadherin、CD44v6和PCNA在非小细胞肺癌组织中的表达及意义

背景与目的:上皮钙依赖粘附蛋白(E-cadherin,E-cad)、CD44v6和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在恶性肿瘤侵袭与转移中发挥重要作用。本研究旨在探讨E-cad、CD44v6和PCNA在非小细胞肺癌(non-small cell lung cancer,NSCLC)及癌旁组织中的表达与NSCLC的侵袭、转移及预后的关系。方法:应用免疫组化EnVision法检测86例NSCLC组织及40例癌旁组织中E-cad、CD44v6和PCNA的表达,并分析与NSCLC的侵袭、转移及预后的关系。结果:E-cad在肺癌组织中的表达率为53.5%(46/86),显著低于癌旁组织(80.0%)(P<0.05),且与NSCLC的分化程度、淋巴结转移和TNM分期有关(P<0.05);CD44v6在肺癌组织中的表达率为44.2%(38/86),在癌旁组织中无表达,且在鳞癌中的表达率(54.0%)显著高于腺癌(30.6%)(P<0.05),并且与淋巴结转移和TNM分期有关(P<0.05);PCNA在肺癌组织中的表达率为48.8%(42/86),在癌旁组织中无表达,且在淋巴结转移组与未转移组间的表达差异有统计学意义(P<0.05)。E-cad与PCNA的表达呈显著性负相关(r=-0.554,P<0.05),而CD44v6与PCNA的表达呈显著性正相关(r=0.688,P<0.05)。单因素生存分析显示E-cad、CD44v6及PCNA的表达与NSCLC患者预后有关。Cox比例风险模型进行多因素生存分析显示;E-cad与临床分期是有意义的预后指标(P<0.05)。结论:E-cad、CD44v6及PCNA的表达与NSCLC的侵袭和转移相关。在NSCLC中联合检测三者的表达对判断预后有参考价值。     

Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma

BACKGROUND: Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. METHODS: One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. RESULTS: Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum alpha-fetoprotein (alphaFP) levels (P = 0.001). Kaplan-Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. CONCLUSIONS: The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high alphaFP levels, p53 overexpression, and poor prognosis in patients with HCC.