转化生长因子β1基因产物在人非小细胞肺癌中的表达研究

目的探讨转化生长因子β１基因表达产物在人非小细胞肺癌中的表达水平及其临床意义。方法采用免疫组织化学方法对７３例人非小细胞肺癌组织中转化生长因子β１基因表达蛋白水平进行了研究。结果转化生长因子β１基因表达水平与肺癌的病期、组织学类型、细胞分化程度，以及肺癌转移有密切关系。转化生长因子β１基因表达水平在腺癌明显高于鳞癌和腺鳞癌，低分化癌明显低于中－高分化癌，Ⅲ、Ⅳ期癌明显低于Ⅰ、Ⅱ期癌，转移癌明显低于原发癌，有淋巴结转移的原发癌明显低于无淋巴结转移的原发癌（Ｐ＜０．０１或Ｐ＜０．０５）。结论转化生长因子β１基因参与调控肺癌的发生、发展和转移过程。     

人非小细胞肺癌中p16基因产物表达研究

目的 探讨人非小细胞肺癌中ｐ１６基因表达产物的表达及其临床意义。方法 应用免疫组织化学ＬＳＡＢ法检测７０例人非小细胞肺癌组织ｐ１６基因产物的表达水平，并以２０例正常肺组织标本作对照。结果 肺癌组织ｐ１６基因产物阳性表达率为６１．３８％，癌旁肺组织为８９．１４％，正常肺组织为８８．２４％。肺癌中Ｐ１６表达水平降低的程度与肺癌细胞分化、原发肿瘤大小和肺癌转移有密切关系（Ｐ〈０．０１或Ｐ〈０．０５），而     

胃癌及其癌旁病变中p16,nm23—H1基因蛋白的表达及意义

目的：应用免疫组化方法探讨ｐ１６蛋白在胃癌发生中的作用。方法：应用免疫组化方法对５７例胃癌切除标本进行Ｐ１６蛋白和ｎｍ２３－Ｈ１基因产物的表达检测。结果：５７例胃癌中Ｐ１６蛋白表达阳阳性率４０／５７（７０．２％），显著低于癌旁无正常胃粘膜（Ｐ〈０．０１）。胃癌高发化组的阳性率显著高于低分化组（Ｐ〈０．０５），不同临床分期（ＵＩＣＣ分期）及有无淋巴结转移的胃癌病例中，Ｐ１６蛋白的表达差异无显著性。癌     

p16基因蛋白在肝癌中的表达及其意义

目的研究ｐ１６基因在肝细胞癌中的表达,探讨ｐ１６基因与肝细胞癌的关系。方法采用免疫组织化学方法,检测２５例肝细胞癌及癌旁组织中ｐ１６基因蛋白的表达。结果①ｐ１６蛋白在肝癌组织与癌周肝组织中的表达差异有显著意义（Ｐ＜０．０１）。②ｐ１６蛋白的表达与ＨＣＣ分化程度关系密切（Ｐ＜０．０５）,而与肿瘤大小、ＡＦＰ值无密切关系（Ｐ＞０．０５）。结论ｐ１６基因蛋白的表达与肝癌的恶性程度有非常密切的关系。ｐ１６基因在肝细胞癌变过程中起一定作用。     

MDR1基因产物在非小细胞肺癌中的表达研究

目的探讨ＭＤＲ１基因表达产物Ｐ－糖蛋白（Ｐ－ｇｐ）在非小细胞肺癌中的表达水平及其临床意义。方法采用免疫组织化学标记链亲和素－生物素法检测１２６例非小细胞肺癌标本中Ｐ－ｇｐ的表达。结果（１）Ｐ－ｇｐ总的阳性表达率为５６．３％（７１／１２６）；（２）腺癌与鳞癌之间，鳞癌与腺鳞癌之间Ｐ－ｇｐ的表达阳性率无显著差异（Ｐ＞０．０５），但腺鳞癌Ｐ－ｇｐ的阳性表达率高于腺癌（Ｐ＜０．０５）；（３）Ｐ－ｇｐ的表达与性别、年龄、肿瘤生长部位、病理分期及是否伴有淋巴结转移无关。结论Ｐ－ｇｐ在非小细胞肺癌中有较高的阳性表达率，且与病理类型有一定关系，提示在非小细胞肺癌尤其是Ｐ－ｇｐ高度表达类型肺癌的化疗中，应重视Ｐ－ｇｐ介导的多药耐药性。     

p16抑癌基因在胆管细胞性肝癌中的表达与预后的关系

目的研究ｐ１６抑癌基因与胆管细胞性肝癌发生、发展及预后的关系。方法用免疫组织化学染色ＳＰ法检测胆管细胞性肝癌３８例、癌旁胆管异型增生组织２６例及正常肝内胆管组织中ｐ１６抑癌基因１６例的表达情况。结果ｐ１６抑癌基因在胆管细胞性肝癌组织中表达率为２６％,明显低于癌旁胆管异型增生组织（６９％,Ｐ＜００１）及正常肝内胆管组织（８１％,Ｐ＜００１）;中、低分化胆管细胞性肝癌ｐ１６抑癌基因表达率（１５％）显著低于高分化胆管细胞性肝癌的ｐ１６抑癌基因表达率（５４％,Ｐ＜００５）;在伴有淋巴结转移和门静脉癌栓的病例中,ｐ１６抑癌基因表达率明显低于相应的对照组（Ｐ＜００５）;ｐ１６抑癌基因阳性病人５年生存率为５６％,而ｐ１６抑癌基因阴性病人５年生存率仅为１４％,二者相比差异有显著意义（Ｐ＜００５）;ｐ１６抑癌基因的表达与癌灶体积、癌灶数目及ＨＢｓＡｇ无关。结论ｐ１６抑癌基因的失表达可能在胆管细胞性肝癌的发生发展中起重要作用;ｐ１６抑癌基因表达与胆管细胞性肝癌的分化程度及有无淋巴结转移和门静脉癌栓形成有关,是判定胆管细胞性肝癌恶性程度及估计预后的重要指标之一。     

胃癌组织中p16,p53蛋白的表达及其临床意义

为探讨ｐ１６，ｐ５３蛋白在胃癌发生、发展中的作用及其临床意义。应用免疫组化方法，对６０例胃癌、１８例胃良性疾病及１５例胃正常组织中ｐ１６，ｐ５３蛋白的表达情况进行检测。结果显示：胃癌组织中ｐ１６蛋白的阳性率（２５％）低于胃良性疾病（６１．１１％）及胃正常组织中的阳性率（６３．３３％），有显著性差异（Ｐ＜０．０５）；而胃癌组织中ｐ５３蛋白的阳性率（６１．６７％）高于胃良性疾病（１１．１１％）及胃正常组织（０），差异非常显著（Ｐ＜０．００１）。ｐ１６，ｐ５３蛋白的表达与胃癌的组织学分化、临床分期及淋巴结转移密切相关，与患者年龄、性别、肿瘤位置无关；ｐ１６蛋白表达还与肿瘤大小有关。研究结果表明，ｐ１６蛋白的失表达发生在胃癌发生、发展的晚期阶段，ｐ１６，ｐ５３蛋白可作为判别胃的良、恶性疾病及胃癌患者预后的一个指标。     

食管癌组织中P16蛋白表达及其临床意义

目的探讨Ｐ１６蛋白表达在食管癌中的临床意义。方法应用免疫组织化学Ｓ－Ｐ法研究了６１例食管癌组织标本中Ｐ１６蛋白表达与食管癌临床病理特征及预后的关系，以及与增殖细胞核抗原（ＰＣＮＡ）的关系。结果Ｐ１６蛋白阳性表达率为４４．３％，其表达与浸润程度、有无淋巴结转移在统计学上无差异（Ｐ＞０．０５），与分化程度、ＴＮＭ分期有关（Ｐ＜０．０５），与ＰＣＮＡ之间存在相关（Ｐ＜０．０１），与术后肿瘤有无转移、复发在统计学上有差异（Ｐ＜０．０５），Ｐ１６阳性表达组的术后生存时间明显高于阴性组（Ｐ＜０．０１）。结论食管癌组织中Ｐ１６蛋白表达对细胞增殖起负性调控作用，检测其表达有助于对食管癌患者预后的判断。     

转移抑制基因nm23—H1在人非小细胞肺癌中的表达研究

目的探讨ｎｍ２３－Ｈ１基因表达产物的表达水平与肺癌发生、发展和转移的关系。方法应用免疫组织化学法研究人非小细胞肺癌细胞中ｎｍ２３－Ｈ１基因表达产物的表达水平。结果ｎｍ２３－Ｈ１在肺癌组织中的表达水平（５４．０３％）明显低于癌旁正常肺组织（７３．４８％，Ｐ＜０．０１）。有淋巴结转移的原发癌ｎｍ２３－Ｈ１表达水平明显低于无淋巴结转移的原发癌（Ｐ＜０．０１）；转移癌组织表达水平明显低于原发癌组织（Ｐ＜０．０１）；低分化肺癌明显低于中－高分化肺癌（Ｐ＜０．０１）。结论ｎｍ２３－Ｈ１基因可能参与肺癌的发生、发展和转移过程的调控，ｎｍ２３－Ｈ１基因表达水平降低，预示肺癌的转移和预后不良。     

抑癌基因p16在人胃癌中的表达及其临床意义

目的 观察ｐ１６基因在胃癌中的表达及其临床应用价值。方法 应用ＳＰ免疫组化及原位杂交技术检测人胃癌中ｐ１６蛋白及其ｍＲＮＡ的表达。结果 ｐ１６蛋白在胃癌中的表达阳性率为６５．８８％（５６／８５）,阴性表达者浸润较深、分化较差,术后生存期较短（Ｐ〈０．０５）;ｐ１６ｍＲＮＡ在胃癌中的表达阳性率为４７．３７％（１８／３８）。结论 ｐ１６基因与胃癌发生、进展有关,原位检测其表达有助于对胃癌生物学行为的了     

肺癌跳跃式纵隔淋巴结转移的临床病理探讨

目的　探索肺癌跳跃式纵隔淋巴结转移的病理特点 ,为合理施行淋巴结清除术提供可靠的理论依据。方法　 1992年 10月至 1998年 6月 ,为 398例肺癌病人施行了根治性肺切除、规范淋巴结清除术 ,对其中 4 7例 ( 2 9 4 % )跳跃式纵隔转移淋巴结病例进行病理学研究。结果　各型或各叶肺癌中 ,跳跃式转移淋巴结分布最密集的部位依次是第 7、4、3、5组淋巴结 ,分别占 2 9 8%、2 4 5 %、14 9%与10 6 % ;就鳞癌与腺癌而言 ,肿瘤长径在 1cm以内者均无跳跃式淋巴结转移 ,跳跃式淋巴结转移率随长径增加而增加 ;低分化腺癌淋巴结转移率明显高于高分化者 (P <0 0 1) ;发生跳跃式淋巴结转移的肿瘤平均长径鳞癌与腺癌分别为 15 3mm与 9 1mm。结论　对肺癌淋巴结的廓清 ,切勿仅凭手触摸或靠肉眼观察淋巴结大小而盲目判定其是否转移或清除。除T1 中肿瘤长径 <1cm的鳞癌外 ,淋巴结的规范清除应重视其跳跃性 ,原则上必须包括同侧胸腔的肺门及上、下纵隔各组淋巴结 ,尤其要重视跳跃式淋巴结转移分布较密集区域 ,即右侧的第 3、4、7组与左侧的第 4、5、7组淋巴结     

21-year-old man with squamous cell carcinoma of the lung

Lung cancer among people in their twenties is rare and accounts for only 0.1-0.4% of all cases. We describe a case of squamous cell carcinoma of the lung in a 21-year-old man. The otherwise healthy patient presented with a 1 month history of cough. Chest radiography showed a well-defined round mass 5 cm in size in the right lower lobe. Computed tomography also showed a 3 cm hilar lymph node. Bronchoscopy revealed a white polypoid mass obstructing the right basal bronchus. Transbronchial biopsy revealed poorly differentiated squamous cell carcinoma of the lung. Clinical diagnosis was T2N1M0, stage IIB lung cancer. Right lower lobectomy with mediastinal lymph node dissection was performed. Lymph node metastases were proven histologically in the pretracheal, subcarinal, hilar, and intrapulmonary regions. Pathological diagnosis was T2N2M0, stage IIIA lung cancer. Endobronchial and mediastinal lymph node metastases were found 2 months after surgery. He received 3 rounds of chemotherapy with cisplatin and docetaxel and irradiation to the right hilum and mediastinum at a total dose of 60 Gy in 30 fractions. He is alive 6 months after surgery.     

T1、T2肺鳞癌及腺癌淋巴结转移特点及其临床意义

目的 研究Ｔ１、Ｔ２肺鳞及腺癌淋巴结转移频度、分布范围及特点,为广泛清扫提供依据。方法 按Ｎａｒｕｋｅ肺癌淋巴结分布图对２５４例Ｔ１、Ｔ２肺鳞癌及腺癌施行了手术切除及广泛肺内、叶间及纵阴淋巴结清扫术并对其进行统计分析。结果 清除淋巴结１６８５组。Ｎ１淋巴结转移率２０．０％,Ｎ２淋巴结转移率为１０．２％。Ｔ１、Ｔ２间淋巴结转移率差异有非常显著性意义（Ｐ〈０．０１）。Ｔ１鳞癌无Ｎ２转移,Ｎ２转移在鳞癌     

肺癌淋巴结转移规律的临床研究

目的 探讨原发性肺癌淋巴结转移频率,分布范围及特点,为广泛廓清提供依据。方法 按Ｎａｒｕｋｅ肺癌淋巴结分布图对３８６例肺癌病人施行了手术切除及广泛肺门、叶间及纵隔淋巴结廓清术。结果 清除淋巴结２６０３组,Ｎ１淋巴结转移率２０．１％,Ｎ２淋巴结转移率１６．２％。Ｔ１,Ｔ２,Ｔ３间淋巴结经差异非常显著。     

Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer

OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is one of the leading causes of death in the world. Lymph node metastasis is not only an important factor in estimating the extent and the metastatic potential of an NSCLC but also in prognosticating the patient outcome. Preoperative prediction of lymph node metastasis might greatly facilitate the choice of appropriate surgical and medical options in patients with NSCLC. METHODS AND RESULTS: Using a cDNA array, we analyzed the expression profiles of 1,289 genes in 92 cancer tissues of NSCLC (37 squamous cell carcinomas and 55 adenocarcinomas). We divided the patients into two groups (classes) for each of various pathological factors, such as lymph node metastasis and pT-stage. For each pair of classes, we searched for an optimal combination of genes to classify the cases using a sequential forward selection algorithm starting from a gene set that showed significant difference in expression between the classes. We used the leave-one-out error cross-validation on a k-nearest neighbor classifier to sequentially choose the gene. Using the optimized set of genes, it was possible to stratify the patients for lymph node metastasis (pN-stage) and pT-stage at, respectively, 100% (23 genes) and 100% (55 genes) for cases with squamous cell carcinomas and 94% (43 genes) and 92% (35 genes) for those with adenocarcinomas. CONCLUSION: We conclude that expression profiling using feature selection provides a powerful means of stratification (personalization) of NSCLC patients and choice in treatment options, particularly for factors such as lymph node metastasis whose radiological diagnosis is presently incomplete.     

Peripheral small squamous cell carcinoma (9 mm) of the lung with metastasis to mediastinal lymph nodes

A 61-year-old man was pointed out a small peripheral lung nodule and mediastinal lymph node swelling on the chest computed tomography (CT). At the operation, it was diagnosed squamous cell carcinoma and right upper lobectomy and nodal dissection were done. The tumor was 9 mm in size and diagnosed as well differentiated squamous cell carcinoma with metastasis to mediastinal lymph nodes. Postoperative radiotherapy was done (50 Gy). The patient is doing well without apparent recurrence 33 months after surgery. We reported a case of peripheral small squamous cell carcinoma (9 mm) of the lung with metastasis to mediastinal lymph nodes.     

E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer

BACKGROUND: E-Cadherin plays a major role in maintaining the intercellular junctions in epithelial tissues. The reduction of E-cadherin expression in cancer cells may be associated with tumor differentiation, metastasis, and a poor prognosis. METHODS: Immunohistochemistry for E-cadherin expression was performed on 109 tumors from patients with non-small cell lung cancer who underwent operations. RESULTS: With respect to membranous immunostaining, 57 carcinomas were E-cadherin-positive, 39 carcinomas E-cadherin-reduced, and 13 carcinomas E-cadherin-negative. The percentage of poorly differentiated tumors in the impaired E-cadherin expression group was significantly higher than that in the E-cadherin-positive group (p = 0.005). Furthermore, the frequency of lymph node metastases in tumors with impaired E-cadherin expression was significantly higher than that in the E-cadherin-positive tumors (p = 0.011). A Cox regression analysis revealed that E-cadherin expression was a significant factor in the prediction of survival for patients with non-small cell lung cancer (p = 0.002). CONCLUSIONS: E-Cadherin expression was associated with tumor differentiation, lymph node metastasis, and prognosis in patients with non-small cell lung cancer.     

Complete mediastinal lymphadenectomy: the core component of the multidisciplinary therapy in resectable non-small cell lung cancer.

There is a great deal of concern about metastasis of lung cancer to regional lymph nodes, due partly to the work of groups of thoracic surgeons in Japan and North America beginning in the 1970s. The classification of regional lymph node stations for lung cancer staging published by Mountain and Dresler has been widely adopted for more than ten years. Anatomic landmarks for 14 levels of intrapulmonary, hilar, and mediastinal lymph nodes stations are designated. Skip transfer and occult lymph node metastasis, confirmed by studies regarding the mode of spread of intrathoracic lymphatic metastasis, are two theoretical bases for complete mediastinal lymphadenectomy of lung cancer. However, whether or not the degree of the dissection influences prognosis, the role of systematic nodal dissection (SND) vs mediastinal lymph node sampling (MLD) in resectable non-small cell lung cancer (NSCLC) remains controversial. A systematic literature search was performed to identify relevant reports, making full use of the 'Cited by,' 'Related Records,' 'References,' and 'Author Index' functions in the PubMed and ISI Web of Science databases. This paper presents a review of the role of mediastinal lymph node distribution and methods of determining suitability for hilar and mediastinal lymphadenectomy based on the four subsets of stage IIIA-N2, balancing the cost vs effect of mediastinal lymph node dissection in resectable NSCLC, focusing on the stage migration bias in clinical trials comparing SND and MLS, recommending a reasonable node dissection sequence, improving the prospects for the perioperative anti-tumor therapy based on mediastinal lymphadenectomy, and evaluating the various preoperative staging techniques. Finally, we believe that, besides the role of complete resection and accurate staging, the complete mediastinal lymphadenectomy is the core component of the lung cancer multidisciplinary therapy, and suggest that the values of lymphadenectomy should be further assessed using decision-tree analysis based on large-scale prospective randomized trials and pooled analysis to evaluate the costs vs effects.     

Sampling or node dissection for intraoperative staging of lung cancer: a multicentric cross-sectional study.

OBJECTIVE: This study compares accuracy of sampling versus formal node dissection in patients with primary lung cancer. PATIENTS AND METHODS: During a 4-month period, 208 consecutive patients (172 men, 36 women) without bulky disease underwent resection for primary lung cancer in three centers. The surgeon first sampled the main lymph node stations, and subsequently performed a radical mediastinal dissection. Endpoints were accuracy of prediction for stage N2 and radicality of node sampling compared to dissection. RESULTS: Resection consisted of 1 segmentectomy, 142 standard lobectomies, 6 bilobectomies, 14 sleeve-lobectomies, and 45 pneumonectomies. There were 108 squamous cell carcinomas, 621 adenocarcinomas, 18 bronchoalveolar carcinomas, 8 large cell carcinomas, 4 adenosquamous carcinomas and 8 neuroendocrine carcinomas. Primary tumor was stage T1 in 49 patients, T2 in 110, T3 in 43, and T4 in 6. Lymph node status (dissection) was N0 in 113, N1 in 35, and N2 in 60 patients. N2 disease concerned a single node in 16, a single node station in 19, and multiple levels in 25. Both N1 and N2 nodes were diseased in 36 patients. Sampling adequately recognized N2 disease in 31 patients (52%). Multiple level N2 was accurately identified in 10 patients (40%). Resection based on sampling would have been incomplete in 53 patients (88%). CONCLUSION: Radical mediastinal dissection is a mandatory adjunct to resection for lung cancer with curative attempt.     

Detection of mediastinal lymph node metastasis from lung cancer with positron emission tomography (PET) using 11C-methionine]

Twenty-five patients with primary non-small cell lung cancer underwent the positron emission tomography (PET) using 11C-methionine to detect the mediastinal lymph node metastasis. We introduced the positron angiography to recognize precisely the anatomical orientation of the mediastinal lymph nodes. The 11C-uptake of the lymph node was expressed with distribution absorption ratio (DAR). A total 107 lymph nodes were examined. The average DAR in metastatic lymph nodes (n = 28) was 3.89 while that of non-metastatic nodes (n = 79) was 2.38 indicating a significant difference (p < 0.001). The most adequate threshold for detection of metastasis was 3.3 with sensitivity of 100%, and specificity of 87.3% and overall accuracy of 89.7%. Metastasis of squamous cell carcinoma was diagnosed more accurately than that of adenocarcinoma. Thus, PET using 11C-methionine may offer a new method to detect the mediastinal lymph node metastasis from lung cancer.