p57KIP2 mRNA在非小细胞肺癌中的表达及临床意义

选取石蜡包埋的44例非小细胞肺癌（NSCLC）患者及12例癌旁肺正常组织的标本制作组织芯片,用地高辛标记的探针、原位杂交法检测p57^KIP2 mRNA的表达情况。发现p57^KIP2 mRNA在癌旁肺正常组织和NSCLC组织中的表达元显著差异（P〉0．05）。鳞癌中阳性表达率明显高于腺癌（P〈0．01）,NSCLC中无淋巴结转移者阳性表达率明显高于有淋巴结转移者（P〈0．01）。p57^KIP2 mRNA的表达有望成为监测NSCLC患者病情发展及评价预后的有用指标。     

TTF-1 和 p63 在肺腺癌与鳞癌的鉴别中的意义简

目的 研究TTF-1和p63在肺腺癌及肺鳞癌中的表达及鉴别诊断中的价值.方法 收集肺鳞癌69例,腺癌62例,采用免疫组织化学PV-9000法分别检测TTF-1和p63在肺腺癌及肺鳞癌中的表达情况.结果 TTF-1在肺鳞癌中未见表达（0/69）,在肺腺癌中的阳性表达率为87.10%（54/62）,TTF-1表达在肺鳞癌与肺腺癌中的表达差异有显著统计学意义（P〈0.01）;P63在肺鳞癌中的阳性表达率为97.10%（67/69）,在肺腺癌中的阳性表达为4.84%（3/62）,p63表达在肺鳞癌与肺腺癌中的表达差异有显著统计学意义（P〈0.01）.结论 根据TTF-1和p63在肺癌组织的存在特异性表达,联合检测两者有助于在肺活检标本中对肺鳞癌和肺腺癌的鉴别诊断.     

肺鳞癌组织中FHIT的表达变化及意义

采用免疫组化SP法检测36例肺鳞癌组织及11例癌旁组织中的脆性氨酸三联体（FHIT）。结果肺癌组织中FHIT蛋白阳性表达率为48．7％,显著低于癌旁组的90．9％（P〈0．01）。高、中分化肺癌组织中FHIT蛋白阳性表达率为60．O％,显著高于低分化组织的36．8％（P〈0．01）;有淋巴结转移的肺癌组织FHIT蛋白阳性表达率为43．7％,显著低于无淋巴转移者的75．0％（P〈0．05）;Ⅰ＋Ⅱ期肺癌组织中FHIT蛋白阳性表达率为52．6％,显著高于Ⅲ期的45．0％（P〈0．05）。认为FHIT在肺鳞癌的发生、发展中发挥作用,可作为判定肺鳞癌发生及转移能力的指标之一。     

HMGB1、VEGF—C在肺癌组织中的表达及临床意义

采用免疫组织化学染色方法检测肺癌组织中高迁移率族蛋白1（HMGB1）及血管内皮生长因子C（VEGF-C）的表达。结果发现,非小细胞肺癌（NSCLC）组织HMGB1及VEGF-C阳性率明显高于癌旁组织（P〈0．05）。HMGB1在肺鳞癌组织中阳性表达率明显低于腺癌组织,而其癌旁组织阳性表达率明显高于腺癌癌旁组织（P均〈0．05）。肺鳞癌组织中VEGF-C阳性表达率明显低于腺癌组织（P〈0．05）;有淋巴结转移NSCLC组织HMGB1及VEGF-C阳性率明显高于无淋巴结转移NSCLC（P均〈0．05）;VEGF-C表达与HMGB1表达呈正相关（P〈0．05）。认为HMGB1和VEGF—C的表达与肺癌组织病理类型和淋巴结转移相关,可作为肺癌转移、治疗和预后判断指标。     

非小细胞肺癌组织蛋白酶D的表达及与预后的关系

目的探讨组织蛋白酶Ｄ（ＣＤ）表达与肺癌患者预后的关系。方法采用链霉抗生物素蛋白－过氧化物酶（Ｓ－Ｐ）快速免疫组织化学法检测非小细胞肺癌（ＮＳＣＬＣ）患者肺癌组织和配对淋巴结标本中ＣＤ表达。结果６６％（４２／６４）的肺癌组织ＣＤ表达阳性，其中鳞癌为５７％（１７／３０），腺癌为７４％（２５／３４）。在３５例转移淋巴结标本中，２０例５７％ＣＤ阳性。Ⅲ～Ⅳ期肺癌病例中，肺癌组织ＣＤ表达高于Ⅰ～Ⅱ期病例（Ｐ＜０．０５）。腺癌伴有淋巴结转移组，ＣＤ表达显著高于淋巴结阴性组（Ｐ＜０．０１）。结论肺癌组织ＣＤ高表达与肿瘤临床分期和腺癌的淋巴结转移关系密切，ＣＤ有可能作为ＮＳＣＬＣ患者的预后指标。     

肺癌前病变、肺癌中FHIT基因表达的临床研究

背景与目的FHIT基因为近年发现的新候选抑癌基因，位于3P14．2跨越FRA3B易脆点，在包括肺癌在内的人类多种肿瘤中均存在异常表达。本研究旨在观察FHIT基因在人肺癌前病变、肺癌中表达情况，探讨FHIT基因在人肺癌发生、发展过程中的可能作用。方法采用免疫组化方法检测298例甲醛固定、石蜡包埋的标本（包括161例肺癌、51例肺癌前病变、30例正常肺组织、23例肺良性病变和33例肺癌转移淋巴结）中FHIT蛋白表达情况。结果FHIT蛋白在正常肺组织及肺良性病变组织中均无失表达；癌前病变组织及肺癌组织中失表达率分别为54．9％（28／51）和59．0％（95／161）：肺癌转移淋巴结组织中FHIT蛋白失表达率78．8％（26／33），各组问比较有显著性差异（P〈0．05）。肺癌组织中FHIT基因表达水平与肺癌组织学类型、肿瘤细胞分化程度、患者P-TNM分期、淋巴结转移程度存在相关性（P〈0．05）。FHIT蛋白失表达组肺癌患者的术后五年生存率显著低于表达组（P〈0．01）。吸烟组患者FHIT基因失表达率69．1％（94／136）显著高于无吸烟组49．5％（49／99）（P〈0．01）。结论FHIT蛋白失表达可能是肺癌发生过程中的早期分子事件，与肺癌的发生、发展及预后有关；吸烟导致FHIT蛋白表达下降可能是诱发肺癌的原因之一。     

p27蛋白在肺腺癌中的表达及临床意义

目的 探讨p27蛋白在肺腺癌的表达及临床意义.方法 应用免疫组化技术检测44例肺腺癌患者的p27蛋白表达,分析p27蛋白表达与性别、年龄、肿瘤大小、临床分期、分化程度和淋巴结转移以及预后的关系.结果 p27蛋白水平与肺腺癌的分化程度相关,与患者的年龄、性别、肿瘤大小、淋巴结转移、TMN分期无关.p27蛋白低表达者的平均生存期（18.6个月）明显低于p27蛋白高表达者（34.5个月）.结论 p27蛋白表达可以作为评价肺腺癌恶性程度和预后的一个重要指标.     

肺鳞癌、腺癌中Survivin表达及其与VEGF和P53表达的相关性研究

目的探讨肺鳞癌、腺癌组织中survivin表达、临床意义及其与VEGF、P53表达的相关性。方法采用免疫组织化学（Envision二步法）检测survivin、VEGF和P53在116例肺鳞癌、腺癌组织及15例肺良性病变组织中的表达情况。结果 survivin、VEGF、P53的阳性率分别为62.1%（72/116）、72.4%（84/116）、55.2%（64/116）,显著高于肺良性病变组织的survivin表达与肺鳞癌、腺癌的低分化（P〈0.05）、淋巴结转移呈正相关（P〈0.05）,与患者预后负相关（P〈0.05）;VEGF和p53的表达与肺癌组织的分化程度、TNM分期及淋巴结转移均有关（P〈0.05）;并且Survivin表达与VEGF、P53表达呈正相关（P〈0.05）。结论 Survivin的表达与肺鳞癌、腺癌的低分化、淋巴结转移正相关;过度表达提示预后不良;Survivin有望成为肺癌诊断和基因治疗的新靶点;survivin、VEGF和P53三者的协同表达可能是促进肺癌恶性进展的重要因素。     

非小细胞肺癌中MMP-2、CD44V6的表达及其临床意义

目的 探讨细胞黏附因子（CD44V6）和基质金属蛋白酶-2（MMP-2）在非小细胞肺癌（NSCLC）组织中的表达及其与肺癌浸润、转移和预后的关系。方法 回顾性分析43例术前未进行放、化疗的肺癌患者的切除标本,采用免疫组化SP法检测肺癌组织中的CD44V6和MMP-2的表达。结果 肺鳞癌与肺腺癌中CD44V6的阳性表达率分别为58．33％（14／24）和68．42％（13／19）;MMP-2的阳性表达率分别为54．16％（13／24）和84．21％（16／19）。CD44V6与MMP-2的阳性表达与淋巴结转移、肺癌病理分期以及术后血行转移显著相关（P〈0．05）,CD44V6阳性表达者的3年生存率为25．62％,5年生存率为6．41％;阴性表达者的3年生存率为64．71％,5年生存率为56．82％,两者差异显著（P=0．000）。MMP-2阳性者的3年生存率为18．8％,5年生存率为8．67％;阴性表达者的3年生存率为66．30％,5年生存率为42．66％,两者差异显著（P=0．0067）。CD44V6和MMP-2的阳性表达呈显著性相关（P：0．007）。结论CD44V6和MMP-2对于肺癌的侵袭、淋巴结转移、术后血行转移以及预后有一定作用。     

TTF-1和p63在肺腺癌与鳞癌的鉴别中的意义

目的研究TTF-1和p63在肺腺癌及肺鳞癌中的表达及鉴别诊断中的价值。方法收集肺鳞癌69例,腺癌62例,采用免疫组织化学PV-9000法分别检测TTF-1和p63在肺腺癌及肺鳞癌中的表达情况。结果 TTF-1在肺鳞癌中未见表达(0/69),在肺腺癌中的阳性表达率为87.10%(54/62),TTF-1表达在肺鳞癌与肺腺癌中的表达差异有显著统计学意义(P0.01);P63在肺鳞癌中的阳性表达率为97.10%(67/69),在肺腺癌中的阳性表达为4.84%(3/62),p63表达在肺鳞癌与肺腺癌中的表达差异有显著统计学意义(P0.01)。结论根据TTF-1和p63在肺癌组织的存在特异性表达,联合检测两者有助于在肺活检标本中对肺鳞癌和肺腺癌的鉴别诊断。     

Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer

STUDY OBJECTIVES: To perform a prospective comparison of direct real-time endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), positron emission tomography (PET), and thoracic CT for detection of mediastinal and hilar lymph node metastasis in patients with lung cancer considered for surgical resection. DESIGN: Prospective patient enrollment. SETTING: University teaching hospital. PATIENTS: One hundred two potentially operable patients with proven (n = 96) or radiologically suspected (n = 6) lung cancer were included in the study. INTERVENTIONS: CT, PET, and EBUS-TBNA were performed prior to surgery for the evaluation of mediastinal and hilar lymph node metastasis. The convex probe EBUS, which is integrated with a convex scanning probe on its tip, was used for EBUS-TBNA. Surgical histology was used as the "gold standard" to confirm lymph node metastasis unless patients were found inoperable for N3 or extensive N2 disease proven by EBUS-TBNA. Main results: EBUS-TBNA was successfully performed in all 102 patients (mean age, 67.8 years) from 147 mediastinal and 53 hilar lymph nodes. EBUS-TBNA proved malignancy in 37 lymph node stations in 24 patients. CT identified 92 positive lymph nodes, and PET identified 89 positive lymph nodes (4 supraclavicular, 63 mediastinal, 22 hilar). The sensitivities of CT, PET, and EBUS-TBNA for the correct diagnosis of mediastinal and hilar lymph node staging were 76.9%, 80.0%, and 92.3%, respectively; specificities were 55.3%, 70.1%, and 100%, and diagnostic accuracies were 60.8%, 72.5%, and 98.0%. EBUS-TBNA was uneventful, and there were no complications. CONCLUSION: Compared to CT and PET, EBUS-TBNA has a high sensitivity as well as specificity for mediastinal and hilar lymph node staging in patients with lung cancer. EBUS-TBNA should be considered for evaluation of the mediastinum early in the staging process of lung cancer.     

胃癌p53基因表达与转移及预后的研究

目的观察胃癌组织ｐ５３基因的超表达及其与预后的关系。方法用抗人Ｐ５３基因蛋白单克隆抗体Ｓ＿Ｐ免疫组织化学方法，观察１２８例胃癌组织ｐ５３表达状况，并对ｐ５３表达与胃癌淋巴结转移状态和术后５年生存率进行比较分析。结果胃癌组织１２８例的ｐ５３表达阳性率为４３８％（５６／１２８）；ｐ５３表达阳性和阴性组的胃癌局部和远处淋巴结转移率分别为６７９％（３８／５６）和５１４％（３７／７２），两者经统计学处理无显著性差异（Ｐ＞００５）。获得随访９８例，胃癌术后５年生存率的随访结果显示，ｐ５３阳性和阴性组分别为３８１％（１６／４２）和３０１％（１７／５６），两组间无统计学意义（Ｐ＞００５）。结论胃癌的发生与ｐ５３基因突变关系密切，并可用免疫组化检测，但Ｐ５３基因蛋白在胃癌组织中的超表达，似不能作为判断胃癌预后的参考指标，应进一步探讨     

Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma

BACKGROUND: The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas. AIMS: To investigate whether CD44v, especially the CD44v2 (v2) isoform, may be a useful prognostic factor for patients with oesophageal squamous cell carcinoma, using a recently developed monoclonal antibody against a v2 epitope. PATIENTS: 233 patients (211 men and 22 women; mean age 61.9 years), with oesophageal squamous cell carcinomas curatively removed without additional treatment between 1987 and 1996 at the National Cancer Center Hospital, were analysed for CD44v expression. METHODS: The expression of CD44v was evaluated immunohistochemically using monoclonal antibodies against epitopes of the standard and variant protein, in paraffin embedded oesophageal squamous cell carcinoma tissue from 233 patients who had undergone cervical, mediastinal, and abdominal lymphadenectomy (three field dissection) for oesophagectomy. The data were evaluated for any correlation with clinicopathological indices or prognosis. RESULTS: Although total CD44 and CD44v6 (v6) were respectively observed in 99% and 97% of the cancer specimens, the expression of v2 was only 30%. Patients whose tumours were v2 positive had a significantly better prognosis than those whose tumours were v2 negative (p = 0.031). Furthermore, in patients without lymph node metastasis, v2 positivity alone was a significant independent factor of prognosis (relative risk of death associated with v2 negativity, 4.7; p = 0.037) in multivariate analysis. CONCLUSIONS: These results indicate that v2 is a useful marker for clinical prognosis in patients with oesophageal squamous cell carcinoma. Particularly in patients without lymph node metastasis, v2 status may thus have implications for the use of adjuvant chemotherapy and/or radiotherapy in patients with oesophageal cancer at an early stage.     

Ⅲ期非小细胞肺癌纵隔淋巴结跳跃式转移的临床意义

目的探讨Ⅲ期非小细胞肺癌(NSCLC)患者纵隔淋巴结跳跃式转移的临床意义。方法65例术后病理证实的NSCLC患者,分为纵隔淋巴结(pN2期)跳跃转移组(21例)及非跳跃转移组(44例),回顾分析两组患者的临床、手术及病理资料。结果两组患者的性别、年龄及肿瘤的病理类型、大小、部位和术后转移情况差异无统计学意义(P均>0·05);非跳跃转移组发生多组淋巴结转移的概率为36.4%(16/44)显著高于跳跃转移组的9.5%(2/21;χ2=8·571,P=0·036)。跳跃转移组患者术后平均生存时间为44个月,5年生存率为41%;非跳跃转移组术后平均生存时间为26个月,5年生存率为21%,两者差异有统计学意义(χ2=9·325,P<0·05)。纵隔淋巴结跳跃式转移可以作为肺癌术后一个独立的预后因素(P=0·003,RR=0·347)。结论纵隔淋巴结跳跃式转移的临床Ⅲ期NSCLC患者生存期较无跳跃式转移的患者长,纵隔淋巴结跳跃式转移可以作为一个独立的生存预后因素;跳跃式转移可能是pN期肺癌中的一个亚群。     

Surgical management of non-small cell lung cancer with synchronous brain metastases

OBJECTIVES: Published series on the synchronous combined resection of brain metastases and primary non-small cell lung cancer are small and scarce. We therefore undertook a multicenter retrospective study to determine long-term survival and identify potential prognostic factors. DESIGN: Our series includes 103 patients who were operated on between 1985 and 1998 for the following tumors: adenocarcinomas (74); squamous cell carcinomas (20); and large cell carcinomas (9). Three patients had two brain metastases, and one patient had three metastases; the remaining patients had a single metastasis. Ninety-three patients presented with neurologic signs that regressed completely after resection in 60 patients and partially, in 26 patients. Neurosurgical resection was incomplete in six patients. Seventy-five patients received postoperative brain radiotherapy. The time interval between the brain operation and the lung resection was < 4 months. Pulmonary resection was incomplete in eight patients. RESULTS: The survival calculated from the date of the first operation was 56% at 1 year, 28% at 2 years, and 11% at 5 years. Univariate analysis showed a better prognosis for adenocarcinomas (p = 0.019) and a trend toward a better prognosis for patients with small pulmonary tumors (T1 vs T3, p = 0.068), N0 stage disease (N0 vs N+, p = 0.069), and complete pulmonary resection (p = 0.057). In a multivariate analysis, adenocarcinoma histology also affected the survival rate (p = 0.03). CONCLUSIONS: It seems legitimate to proceed with lung resection after complete resection of a single brain metastasis, at least in patients with an adenocarcinoma and a small lung tumor and without abnormal mediastinal lymph nodes seen on the CT scan or during mediastinoscopy.     

耐多药相关蛋白在人非小细胞肺癌组织中的表达

目的　检测人非小细胞肺癌组织中耐多药相关蛋白（ＭＲＰ） 的表达,探讨其与瘤组织学类型、分化程度、临床分期及预后的关系。方法　采用免疫组化方法及逆转录聚合酶链反应（ＲＴＰＣＲ）技术,分别检测了９２ 份人非小细胞肺癌石蜡组织中ＭＲＰ的表达及１６ 份人非小细胞肺癌新鲜组织中ＭＲＰ基因的表达。结果　９２ 份人非小细胞肺癌组织中（ 鳞癌４３ 例,腺癌４９ 例）ＭＲＰ表达阳性检出率为５４％（５０／９２） ,１６ 份人非小细胞肺癌组织中ＭＲＰ基因表达阳性检出率为３１％ （５／１６）。ＭＲＰ在腺癌中的表达阳性率明显高于鳞癌（ Ｐ＜ ０－０５） ,ＭＲＰ表达与瘤分化程度、肿瘤大小及淋巴结转移无显著相关。ＭＲＰ阳性患者术后５ 年生存率为１６％ （８／５０）,ＭＲＰ 阴性患者术后５ 年生存率为５２％ （２２／４２） ,二者经统计学处理,差异有显著性（ Ｐ＜ ０－０５）。ＭＲＰ阳性患者术后５ 年生存率有随其瘤组织中该蛋白表达阳性程度的增加而降低之趋势。结论　非小细胞肺癌患者瘤组织中ＭＲＰ的表达与瘤组织学类型及预后明显相关。     

Endobronchial ultrasonography for mediastinal and hilar lymph node metastases of lung cancer

STUDY OBJECTIVES: Conventional radiologic procedures are frequently unreliable in the diagnosis of mediastinal and hilar lymph node metastases of lung cancer. In order to improve diagnostic accuracy, we performed endobronchial ultrasonography (EBUS) during bronchofiberscopic examinations of patients with lung cancer. METHODS AND PATIENTS: To evaluate mediastinal and hilar lymph node metastases, EBUS was performed prospectively using a radial scanning probe of 20 MHz through a bronchofiberscope. RESULTS: We observed hilar lymph nodes (10R, 11R superior, 11R inferior, 12R, 10L, 11L, 12L) in 20 of 37 patients who underwent EBUS, and we could clearly identify whether direct invasion of the pulmonary artery by a lymph node had occurred. Of the 27 patients who showed no hilar lymph nodes on chest CT scan, lymph node swellings < 10 mm or > or = 10 mm in diameter were identified by EBUS in 9 patients and 2 patients, respectively. Interestingly, EBUS also revealed that the pulmonary artery was directly invaded by an interlobar lymph node < 10 mm in diameter in one patient. In most patients, lymph node 7 was easily identified and was clearly differentiated from the surrounding esophagus, vessels, and mediastinal fat tissue by EBUS. However, fused lymph nodes or lymph nodes with low central density when visualized by chest CT scan were occasionally observed as independent lymph nodes by EBUS. When compared with the pathologic diagnosis of lymph node metastasis in 16 patients who underwent surgery, the most specific and sensitive method for identifying lymph node metastases were EBUS alone (92%) and EBUS in combination with CT scan (100%), respectively. The overall accuracy of EBUS was 94% for the diagnosis of direct invasion of the pulmonary arteries by a hilar lymph node. CONCLUSIONS: EBUS in combination with conventional radiologic tools may contribute to improved staging, especially in surgical cases with hilar lymph node metastases.     

可切除性肺癌胸内淋巴结转移的临床研究

目的　探讨可切除性肺癌的胸内淋巴结转移规律。方法　收集１９９２ 年１ 月～１９９８ 年７月可切除性肺癌１６０ 例,在肺癌术中分区摘除肺门淋巴结（Ｎ１） 和纵隔淋巴结（Ｎ２）,记录各区淋巴结的数量、大小和颜色,按区检查每一个淋巴结有无转移癌。结果　１６０ 例肺癌中有淋巴结转移者９９ 例（６１－９％ ）,Ｎ２ 转移者７３ 例（４５－６％ ） 。离肺门或肺根部最近的１１、１０ 、７、５ 和４ 区淋巴结的转移频度较高,较远的９、６、３、２ 和１ 区则明显降低。淋巴结≥２ ｃｍ 的癌转移度为６０－７ ％ 、≥１ ｃｍ 为１５－５％ 、＜ １ｃｍ 为４－３％ 。有转移癌的最小淋巴结为０－２ ｃｍ 。小细胞肺癌（ＳＣＬＣ）的淋巴结转移明显高于非小细胞肺癌（ＮＳＣＬＣ）（ Ｐ＜ ０－０５） 。结论　多数肺癌的淋巴结转移遵循由近向远、由下向上、由肺内经肺门向纵隔顺序转移的规律。淋巴结转移与肿瘤的部位、大小、病程均无关,ＳＣＬＣ更易发生淋巴结转移。确诊淋巴结有无转移癌必须依靠病理检查。     

Expression of Bax protein in gastric carcinomas. A clinicopathological and immunohistochemical study

BACKGROUND AND STUDY AIMS: Reduced Bax protein expression has been shown to be a negative prognostic factor in patients with breast, ovarian, colorectal, esophageal and pancreatic cancer. Our aim was to immunohistochemically study Bax protein expression in gastric carcinomas and correlate its expression with clinicopathological parameters and prognosis. PATIENTS AND METHODS: Immunohistochemistry was performed, using a monoclonal antibody against bax, in paraffin-embedded tumor specimens from 47 cases of gastric cancer. RESULTS: Positive staining for the Bax protein was found in 20/47 (42.4%) adenocarcinomas examined. Negative Bax protein expression in tumour cells was correlated with lymph node metastasis (P < 0.05), and degree of differentiation (p < 0.05). Univariate analysis showed that the variables with a significant negative impact on survival were: high TNM tumour stage, depth of penetration in the gastric wall, lymph node involvement, and Bax protein expression. Multivariate analysis showed that the only variable with an impact on survival was Bax protein expression (p < 0.05, Relative Risk: 3.34). Kaplan-Meier curves showed that the 5-year survival was 36.8% in cases with positive compared with 16% in cases with negative Bax protein expression (p = 0.0427). CONCLUSION: Negative Bax expression in gastric cancer is associated with de-differentiation, lymph node metastases, and poor clinical prognosis. Bax protein expression might play an important role in the development and phenotypic differentiation of gastric carcinomas and tumor progression.