TTF-I和p63在NSCLC组织中的表达及临床意义

背景与目的 TTF-1和p63近年被发现在肺癌中有高表达,并可能与肺癌的发生、发展相关.本文旨在研究TTF-1和p63在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达,并探讨其临床意义.方法 收集长海医院2008年原发性NSCLC组织标本404例和良性肺疾患(benign pulmonary disease,BPD)组织标本28例.采集病例相关的临床病理资料.采用免疫组化EnVision两步法分别检测TTF-1和p63蛋白在NSCLC中的表达并对其结果进行分析.结果 TTF-1和p63蛋白在NSCLC中阳性表达率分别为51.7%(209/404)和37.9%(153/404),而在BPD对照组病灶均为阴性表达.TTF-1蛋白在女性、不吸烟及无症状者升高明显(P<0.05),主要表达于肺腺癌(191/227),其诊断敏感性和特异性分别达84.1%和89.8%,阳性表达率随着腺癌分化程度的增加而增加(P<0.001).p63蛋白阳性表达多见于男性、吸烟人群(P<0.001),对肺鳞癌的诊断敏感性高达95.5%.特异性为98.8%.p63阳性表达与鳞癌的分化程度正相关(P=0.008).与临床分期呈负相关(P=0.002),但与其他因素无关.Logistic多因素分析显示,病人吸烟史及肿瘤病理类型为影响TTF-1、p63表达的因素.两者联合检测,TTF-1(+)/p63(-)表型腺癌占93.1%,TTF-1(-)/p63(+)表型鳞癌占98.6%,TTF-1与p63的阳性表达呈负相关(r=-0.757,P<0.001).结论 NSCLC中TTF-1、p63的表达与病人吸烟史及肿瘤病理类型密切相关,二者分别是肺腺癌、鳞癌有效的生物学标志物,其联合应用有利于NSCLC的诊断及鉴别.     

CK7、TTF-1、p63在非小细胞肺癌患者体内表达变化的意义研究

目的 观察细胞角蛋白7(CK7)、甲状腺转录因子-1(TTF-1)、p63蛋白在非小细胞肺癌患者体内的表达情况,并分析其临床意义.方法 选取80例非小细胞肺癌患者的非小细胞肺癌组织作为非小细胞肺癌组,另选取其正常肺组织作为对照组.观察非小细胞肺癌组织中CK7、TTF-1、p63的阳性表达率,比较不同临床病理特征非小细胞肺癌患者CK7、TTF-1、p63阳性表达率的差异,分析影响非小细胞肺癌患者CK7、TTF-1、p63阳性表达率的因素.结果 非小细胞肺癌组织中的CK7、TTF-1、p63阳性表达率均明显高于正常肺组织(P﹤0.001);不同TNM分期、淋巴结转移、组织学分型和分化程度非小细胞肺癌患者CK7、TTF-1、p63的阳性表达率比较,差异均有统计学意义(P﹤0.05),不同年龄、性别非小细胞肺癌患者CK7、TTF-1、p63的阳性表达率比较,差异均无统计学意义(P﹥0.05);多因素Logistic回归分析结果显示,淋巴结转移和组织学分型是非小细胞肺癌患者CK7、TTF-1、p63阳性表达的影响因素(P﹤0.05).结论 CK7、TTF-1、p63在非小细胞肺癌患者体内高表达,且与患者的淋巴结转移情况和组织学分型密切相关.     

非小细胞肺癌组织COX-2和p53表达及其临床意义的探讨

目的:探讨COX-2 和突变性p53蛋白在非小细胞肺癌(NSCLC)发生、发展中的作用机制及两者之间的相关性.方法:流式细胞仪检测80例NSCLC组织和20例癌旁正常肺组织中COX-2 蛋白、突变型p53蛋白的表达情况.结果:NSCLC组织中COX-2蛋白较正常组织高表达,P<0.01.COX-2表达与有无淋巴结转移(P=0.002)和肿瘤大小(P=0.045)有关,与NSCLC患者性别、TNM分期、分化程度和组织学类型无关,P>0.05.NSCLC组织中p53蛋白较正常组织高表达,P<0.01.p53蛋白表达与有无淋巴结转移(P=0.01)有关;而与NSCLC患者性别、肿瘤的大小、TNM分期、肿瘤分化程度和组织学类型无关,P>0.05.NSCLC组织中p53和COX-2蛋白同时阳性表达率为47.82%(22/46),p53阴性COX-2蛋白阳性表达率为58.82%(20/34),两者表达无相关性,P=0.33.结论:COX-2的过表达及p53蛋白突变与NSCLC的发生发展有关,两者之间无相关性.     

非小细胞肺癌组织中p63蛋白的表达及其意义

目的 检测p63蛋白在非小细胞肺癌（NSCLC）组织中的表达情况，并探讨其与NSCLC临床病理特征的关系。方法 采用免疫组化（S-P法）检测p63蛋白在76例NSCLC及12例癌旁肺组织中的表达情况。结果 p63蛋白在NSCLC组织中的阳性表达率为55。3％（42／76），而在癌旁肺组织中无阳性表达，两者比较有非常显著性差异（P〈0．01）。p63蛋白的表达与NSCLC病理类型密切相关（P〈0.01），其在肺鳞癌中的阳性表达率（80．0％）显著高于在肺腺癌（33.3％）和肺腺鳞癌（36.4％）中的阳性表达率；在不同分化程度的肺鳞癌中p63的阳性表达率相互比较有显著性差异（P〈0.05）。p63蛋白的表达与NSCLC的TNM分期、淋巴结转移、术后复发及生存期均无明显相关（P〉0.05）。结论 p63蛋白在NSCLC中表达上调，可能是1个有价值的诊断肺鳞癌和判断肺鳞癌分化的标志物。     

Survivin、p53、Bcl-2蛋白在非小细胞肺癌中的表达及意义

目的:探讨Survivin基因在非小细胞肺癌(NSCLC)中的表达,以及与P53,Bcl-2蛋白表达的相互关系。方法:应用免疫组织化学法(SP)检测80例NSCLC肿瘤组织、20例肺良性病变组织中Survivin蛋白、P53蛋白、Bcl-2蛋白表达情况,并将结果进行了相关分析。结果:Survivin蛋白在肺良性病变组织中不表达,在61.3%(49/80)的NSCLC组织中有表达,且Survivin的表达与肺癌患者的TNM分期有关,但与肺癌的细胞类型、分化程度及淋巴结转移无明显关系;肺癌组织p53蛋白阳性表达率55.0%(44/80),与肺癌的TNM分期及淋巴结转移有关,肺良性病变组织中无p53蛋白表达;肺癌组织Bcl-2蛋白阳性表达率50.0%(40/80)明显高于肺良性病变组织的10.0%(2/20),其中鳞癌组织的表达率62.2%,明显高于腺癌组织的表达率34.3%(P<0.05);肺癌组织中P53,Bcl-2蛋白与Survivin蛋白表达显著相关(P<0.05)。结论:Survivin蛋白在肺癌组织中表达上调,提示该基因对NSCLC的发生发展起重要作用。Survivin基因有望成为肺癌基因治疗的新靶点;Survivin蛋白表达与肺癌的TNM分期密切相关,提示可作为判断病情和评价预后的指标。Sur vivin蛋白的表达与p53蛋白、Bcl-2蛋白的表达均呈正相关,三者在肺癌的发生中可能起协同作用。     

TC-1在非小细胞肺癌的表达及与淋巴结转移的关系

目的:探讨TC-1蛋白在非小细胞肺癌(NSCLC)组织中的表达及其在病理分类、分级、TNM分期中的差异性,为进一步研究TC-1在NSCLC中的作用及其机制提供依据。方法:采用免疫组化EnVinsion法检测TC-1蛋白在95例非小细胞肺癌中的表达,统计学分析其在病理分类、分级及临床TNM分期及淋巴结转移与否的差异性。结果:免疫组化结果显示TC-1阳性表达主要位于胞浆中和部分胞核。肺鳞癌和腺癌总阳性率分别为63.46%、72.09%,差异性不显著(P=0.154)。鳞癌高、中、低分级阳性率分别为20.00%、65.51%、72.22%,经Kruskal-Wallis H检验无明显差异性(P=0.075)。腺癌的高、中、低分级的阳性率分别是33.33%、65.21%、88.23%,差异性非常显著(P=0.005)。NSCLC(鳞癌、腺癌)的TNM分期Ⅰa、Ⅰb、Ⅱa、Ⅱb、Ⅲa、Ⅲb的表达强度经检验差异性显著(P=0.029)。有淋巴结转移者原发灶阳性率为90.57%(48/53)、无淋巴结转移者原发灶阳性率为38.09%(16/42),经Mann-Whitney U秩和检验差异性非常显著(P=0.000)。53例伴淋巴结转移的NSCLC原发灶与淋巴结转移灶阳性表达相关性用Spearman检验,有相关性(r=0.39,P=0.000)。结论:TC-1在非小细胞肺癌(NSCLC)组织中高表达,TC-1表达与病理分型、鳞癌分级无关,与腺癌分级、NSCLC TNM分期、淋巴结转移与否相关。提示TC-1在肺癌组织中表达高低与淋巴结转移密切相关。     

p63和TTF-1在肺癌组织中的表达及鉴别诊断意义

目的:探讨p63和TTF-1蛋白在肺癌不同组织类型中的表达特点及鉴别诊断的价值。方法:应用免疫组织化学S-P法检测116例原发性肺癌组织中p63和TTF-1蛋白的表达情况。结果:p63在肺鳞癌中阳性表达率为100%(47/47),而在其他组织类型肺癌中基本不表达。TTF-1在肺小细胞癌和肺腺癌中阳性表达率分别为93.3%(14/15)和93.5%(43/46),而在鳞癌中未见表达。结论:p63可作为肺鳞状上皮源性肿瘤标记物,是判断鳞癌的可靠指标。TTF-1可作为肺小细胞癌、腺癌的特异性标记。联合检测p63和TTF-1对肺癌不同组织类型的诊断、鉴别诊断具有较高的实用价值,尤其可作为鉴别分化差的鳞癌、腺癌和小细胞癌的指标。     

Trx-1和COX-2在非小细胞肺癌中的表达及意义

目的探讨硫氧化还原蛋白1(thioredoxin,Trx-1)和COX-2在非小细胞肺癌中的表达及其临床意义。方法免疫组织化学方法检测63例非小细胞肺癌组织和20例癌旁正常肺组织中Trx-1和COX-2的表达。结果63例非小细胞肺癌组织中Trx-1和COX-2均呈高表达,分别为63.5%（40/63）和59.1%（37/63）,20例正常肺组织Trx-1阳性3例,COX-2阳性2例,差异具有统计学意义(P<005)。Trx-1在低分化癌组织中阳性表达率高于中高分化癌组织,差异具有统计学意义(P<0.05);在不同TNM分期的非小细胞肺癌组织中,阳性表达率差异具有统计学意义(P< 0.05),在有淋巴结转移的癌组织中阳性表达率高于无淋巴结转移者,差异具有统计学意义(P<0.05)。COX-2的表达与TNM分期及淋巴结转移差异具有统计学意义(P<0.05)。结论Trx-1和COX-2的表达与非小细胞肺癌患者预后密切相关。     

血管紧张素Ⅱ1型受体在肺鳞癌、腺癌中的表达及与Survivin、p53相关性研究

目的:探讨在肺鳞癌、腺癌组织中血管紧张素Ⅱ1型受体(AngiotensinⅡtype-1 receptor,AT1R)的表达及临床意义,并探讨AT1R表达及与Survivin、p53之间的相关性。方法:采用免疫组织化学方法(SP法)检测72例肺鳞癌、腺癌组织和12例癌旁正常组织中AT1R、Survivin、p53的表达。结果:AT1R在肺鳞癌、腺癌组织中的阳性表达率为48.6%,在正常组织中未检出阳性结果。AT1R阳性表达率与淋巴结转移及TNM分期呈正相关(P<0.05),与组织学类型、病理分级及是否吸烟无相关性(P>0.05)。AT1R阳性表达患者p53蛋白、Survivin阳性表达率分别为71.4%和74.3%,AT1R不表达患者p53蛋白及Survivin阳性表达率分别为29.7%和40.5%。AT1R表达与Survivin、p53蛋白表达呈正相关(P<0.01)。结论:AT1R参与了肺鳞癌、腺癌的恶性增殖和侵袭,其表达能为肺癌诊断、治疗、判断预后提供新的依据。     

非小细胞肺癌患者肿瘤标志物的表达及与临床病理的关系

目的探讨非小细胞肺癌(NSCLC)患者蛋白激酶1活化受体(RACK1)、甲状腺转录因子1(TTF-1)和细胞角蛋白7(CK7)的表达及与临床病理之间的关系。方法选取2014年12月至2017年6月间重庆市合川区人民医院收治的110例NSCLC患者,以病理活检标本及手术时所取肺癌组织标本作为研究组,以距离癌组织2cm的癌旁组织标本作为对照组。采用免疫组化法检测RACK1、TTF-1和CK7蛋白的表达情况,分析三项指标与临床病理参数的关系,采用Pearson相关性分析方法分析RACK1、TTF-1和CK7蛋白表达的相关性。结果研究组RACK1、TTF-1和CK7蛋白阳性表达率均明显高于对照组,差异均有统计学意义(均P<0.05)。腺癌患者RACK1、TTF-1和CK7的阳性表达率显著高于鳞癌,高分化患者RACK1、TTF-1和CK7阳性表达率显著低于中低分化患者,临床分期Ⅰ~Ⅱ期患者RACK1、TTF-1和CK7阳性表达率显著低于Ⅲ~Ⅳ期患者,无淋巴结转移患者RACK1、TTF-1和CK7的阳性表达率明显低于有淋巴结转移患者,差异均有统计学意义(均P<0.05)。RACK1、TTF-1和CK7蛋白的表达与患者性别和年龄无关,差异无统计学意义(P>0.05)。Pearson相关性分析显示,NSCLC组织中RACK1表达与TTF-1和CK7表达均呈正相关关系,差异均有统计学意义(均P<0.05)。结论 RACK1、TTF-1和CK7在NSCLC组织中表达可能与NSCLC的发生发展有关,提示RACK1、TTF-1和CK7可作为新的分子靶点用于NSCLC的早期诊断及病情评估。     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

Occupational and environmental radiation and cancer

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

肾上腺素能β受体与肿瘤生长及转移

大量研究表明肿瘤细胞可表达β受体，而一些神经递质、药物和社会心理因素可能通过β受体影响肿瘤的生长和转移，β受体激动剂、β受体阻滞剂以及抑郁等社会心理因素可加强或削弱这种作用。这为表达β受体肿瘤的治疗开辟了新的道路，提供了新的治疗靶点。     

Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance

This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can significantly disrupt important molecular pathways in the networks of communications needed to sustain orderly tissue/organ structure and function. However, genetic lesions can also, themselves, be induced by abnormal cell interactions initiated by extrinsic carcinogenic agents such as chemicals, viruses, hormones and radiation. The evidence shows that, irrespective of the initiating cause, it is this miscommunication in the region of a developing tumour and its metastases that is ultimately responsible for the emergence and progression of the disease. The article describes how this information collectively, provides a framework for designing specific novel therapeutic approaches targeting the cell and tissue interactions driving tumour metastasis and its manifold effects on the whole body.     

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60–3.53) and 1.64 (95% CI 1.02–2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63–1.13) for CM and 1.03 (95% CI 0.95–1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.