12例化生性乳腺癌临床病理分析

目的分析化生性乳腺癌的临床病理特征及其与基底样乳腺癌的关系。方法应用免疫组化法检测12例化生性乳腺癌中ER、PR、HER2、CK5/6、CK14、P63和EGFR的蛋白表达,应用荧光原位杂交检测化生性乳腺癌中的HER2基因扩增,用电镜观测化生性乳腺癌的超微结构,对CK5/6在化生性乳腺癌诊断中的敏感性及化生性乳腺癌预后因素进行分析。结果 12例化生性乳腺癌的ER、PR及HER2免疫染色均为阴性,而CK5/6则为100%(12/12)的阳性表达,CK14、EGFR及P63的阳性表达率分别为75.0%(9/12)、83.3%(10/12)和66.7%(8/12)。FISH实验结果显示化生性乳腺癌中无HER2基因扩增(Ratio1.8)。超微结构观察见癌细胞胞浆内有张力原纤维丝、细肌丝和密体。CK5/6、CK14、P63和EGFR免疫染色阳性反应之间有显著统计学意义(P=0.000)。年龄和淋巴结转移与化生性乳腺癌的预后具有显著统计学意义(P=0.004)。结论化生性乳腺癌为基底样乳腺癌表型。CK5/6、CK14、P63和EGFR可作为化生性乳腺癌的诊断标记物,其中CK5/6比CK14和P63更为敏感。化生性乳腺癌的预后与年龄和淋巴结转移有关。     

浸润性乳腺癌中CK5/6、EGFR以及激素受体表达的相关性分析

目的:了解浸润性乳腺癌中CK5/6、EGFR以及激素受体的表达情况及其相关性.方法:采用HE、免疫组化(EnVision法)检测146例浸润性乳腺癌.结果:146例患者均为女性,年龄33-82岁,平均54岁.组织学上部分肿瘤细胞显著多形性,核分裂象多见.免疫组化:146例浸润性乳腺癌中31例为ER、PR、HER2三阴性乳腺癌.CK5/6在浸润性乳腺癌及三阴性乳腺癌中的表达率分别为17.8%(26/146)和54.8%(17/31),EGFR在CK5/6阳性和CK5/6阴性乳腺癌中的表达率分别为65.3%(17/26)和16.6%(20/120).Ki-67在CK5/6阳性乳腺癌中的表达率显著高于CK5/6阴性乳腺癌中的表达率.结论:基底细胞样型乳腺癌在三阴性乳腺癌中发病率较高;Ki-67在基底细胞样型乳腺癌中高表达率提示该肿瘤预后差.     

浸润性乳腺癌中CK5/6、EGFR以及激素受体表达的相关性分析

目的：了解浸润性乳腺癌中CK5/6、EGFR以及激素受体的表达情况及其相关性.方法：采用HE、免疫组化（EnVision法）检测146例浸润性乳腺癌.结果：146例患者均为女性,年龄33-82岁,平均54岁.组织学上部分肿瘤细胞显著多形性,核分裂象多见.免疫组化：146例浸润性乳腺癌中31例为ER、PR、HER2三阴性乳腺癌.CK5/6在浸润性乳腺癌及三阴性乳腺癌中的表达率分别为17.8%（26/146）和54.8%（17/31）,EGFR在CK5/6阳性和CK5/6阴性乳腺癌中的表达率分别为65.3%（17/26）和16.6%（20/120）.Ki-67在CK5/6阳性乳腺癌中的表达率显著高于CK5/6阴性乳腺癌中的表达率.结论：基底细胞样型乳腺癌在三阴性乳腺癌中发病率较高;Ki-67在基底细胞样型乳腺癌中高表达率提示该肿瘤预后差.     

不同分子分型的HR阴性乳腺癌临床病理特征及预后的研究

目的： 探讨激素受体 (hormone receptor,HR)阴性浸润性乳腺癌的分子分型情况,以及不同分子分型的临床病理特征和预后?方法：应用组织芯片技术及免疫组化将所选200例HR阴性[包括雌激素受体 (estrogen receptor,ER)和孕激素受体 (progesterone receptor ,PR)均为阴性]浸润性乳腺癌,依据HER2及基底细胞标记[包括细胞角蛋白5/6 (cytokeratin 5/6,CK5/6),细胞角蛋白14 (cytokeratin14,CK14)及上皮生长因子受体 (epidermal growth factor receptor,EGFR)]表达情况,分为以下类型：HER2过表达型、基底细胞样型及裸型;HER2过表达型又分两类亚型：单纯性HER2过表达型、基底细胞样-HER2过表达型;比较不同分子分型乳腺癌的病理特征及预后。结果：HR阴性乳腺癌具有病理分级高,临床分期晚,发病年龄近绝经期等特点,各分型间差异无统计学意义;基底细胞样-HER2过表达型远处转移率高于基底细胞样型 (P<0.05),其5年无病生存率及5年总生存率低于各分型 (P<0.05)。 结论：基底细胞样型并非影响乳腺癌预后的独立因素,基底细胞样-HER2过表达型乳腺癌较基底细胞样型具有更差的预后情况。     

HER2和ER/PR双阳性表达的Ⅰ～Ⅲ期乳腺癌患者生存分析

目的:研究HER2受体和激素受体(ER和/或PR)双阳性表达乳腺癌患者预后,以指导临床治疗.方法:收集我院2002年1月～2003年12月可手术且HER2阳性表达乳腺癌患者93例,HER2阳性表达采用免疫组化方法及荧光原位杂交方法确认,其中ER/PR阳性者59例,ER和PR阴性者34例,两组患者的临床特征(年龄、病理类型、肿瘤直径、淋巴结转移数目、治疗方案)无统计学差异,分析两组乳腺癌患者的5年总生存率及无病生存率.结果:HER2和ER/PR双阳性表达乳腺癌患者与HER2单阳性表达5年总生存率分别为92%和88%(P=0.380),5年无病生存率分别为81%和82%(P=0.999).结论:辅助蒽环类化疗及三苯氧胺内分泌治疗不能改善HER2和ER/PR双阳性乳腺癌患者的总生存率和无病生存率,对双阳性患者应加强治疗力度.     

HER3在乳腺癌中的表达及临床意义

目的探讨乳腺癌患者HER3与HER2、ER和PR之间的关系及其对乳腺癌预后的影响。方法采用免疫组织化学SP法检测癌组织中HER3、HER2、ER和PR蛋白的表达,对患者随访,随访终点为总生存时间(overall survival,OS)。结果 HER2、HER3、ER和PR在136例乳腺癌患者中的阳性表达率分别为:50%、41.18%、60.9%和27.21%。HER3与年龄、淋巴结转移、分期、肿瘤类型以及化疗状态的差异无统计学意义(P>0.05)。HER3阳性与阴性患者OS差异有统计学意义(P=0.015)。HER3(+)HER2(+)组乳腺癌患者较其他组OS明显缩短(P=0.047)。HER3的表达与PR表达无明显关系(P=0.214),但可抑制ER产生(P=0.001)。HER2阳性和HER3的过度表达高度相关(P=0.000)。结论HER3可作为独立的临床预后因子,HER3阴性患者OS较长。     

DNA-PKcs表达与乳腺癌临床病理特征关系的研究

目的:研究DNA依赖蛋白激酶催化亚单位(DNA-PKcs)表达与浸润性乳腺癌临床病理特征的关系。方法:应用组织芯片技术和免疫组织化学方法检测101例浸润性乳腺癌中DNA-PKcs以及ER、PR、c-erbB-2的表达情况,采用χ2检验及Spearman秩和相关检验分析结果。结果:DNA-PKcs表达与浸润性乳腺癌的肿瘤大小、淋巴结转移数量、TNM分期均呈负相关(分别为r=-0.319,P=0.001;r=-0.378,P=0.000;rs=-0.428,P=0.000);与ER表达呈正相关(rs=0.279,P=0.005);与患者年龄、肿瘤组织学分级、及PR、c-erbB-2表达的关系无统计学意义(P>0.05)。结论:DNA-PKcs低表达与浸润性乳腺癌的进展及淋巴结转移关系密切,有可能成为预测乳腺癌预后重要的生物学指标。     

乳腺癌组织中EGFR、IGF-1R、HER2/neu和p53蛋白的表达及意义

目的:探讨乳腺癌组织中表皮生长因子受体(EGFR)、胰岛素样生长因子- 1 受体(IGF 1R)、HER2/neu和p53的蛋白表达状况与临床分期、病理和生存的关系。方法:用免疫组织化学SP法检测210例乳腺癌患者原发肿瘤组织和其中49 例转移淋巴结组织中的EGFR、IGF -1R 、HER2/neu和p53蛋白表达水平。结果:210 例乳腺癌原发组织中,EGFR、IGF -1R 、HER2/neu和p53的表达阳性率分别为47. 1% ( 99/210 )、40. 5% ( 85/210 )、63. 8% (134/210)和55. 7% (117/210); 49 例乳腺癌中, HER2/neu 11 例、IGF 1R 6 例、p53 和EGFR各2例,在转移淋巴结组织与原发肿瘤组织中表达程度不一致。除IGF 1R外,不同的TNM分期,EGFR、HER2/neu、p53表达阳性率差异有统计学意义,P值分别为0 .25、0. 005、0 .025和0. 01;但均与病理类型无关,P值分别为0. 002、0. 6、0. 3和0 .1。Cox模型回归分析TNM分期、病理类型、年龄、EGFR、IGF- 1R 、HER2/neu、p53、ER 和PR的表达9 个因素对生存时间影响, TNM分期、年龄和IGF 1R表达状况的增加对生存时间为危险因素,P<0 .05,OR>1。3 年生存率为87%,5 年生存率为66%,中位生存期85个月。结论:检测乳腺癌组织中EGFR、IGF -1R、HER2/neu和p53的蛋白表达对乳腺癌的诊断、指导治疗及评价预后有重要的临床意     

DNA-PKcs表达与乳腺癌临床病理特征关系的研究

目的：研究DNA依赖蛋白激酶催化亚单位（DNA-PKcs）表达与浸润性乳腺癌临床病理特征的关系。方法：应用组织芯片技术和免疫组织化学方法检测101例浸润性乳腺癌中DNA-PKcs以及ER、PR、c-erbB-2的表达情况,采用χ2检验及Spearman秩和相关检验分析结果。结果：DNA-PKcs表达与浸润性乳腺癌的肿瘤大小、淋巴结转移数量、TNM分期均呈负相关（分别为r=-0.319,P=0.001;r=-0.378,P=0.000;rs=-0.428,P=0.000）;与ER表达呈正相关（rs=0.279,P=0.005）;与患者年龄、肿瘤组织学分级、及PR、c-erbB-2表达的关系无统计学意义（P〉0.05）。结论：DNA-PKcs低表达与浸润性乳腺癌的进展及淋巴结转移关系密切,有可能成为预测乳腺癌预后重要的生物学指标。     

浸润性乳腺癌钼靶X线表现与受体水平的关系

目的 对浸润性乳腺癌的钼靶X线表现与雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)的表达状况进行比较,分析其相关性.方法 70例经手术病理证实的浸润性乳腺癌,术前均行乳腺钼靶X线检查,术后病理标本经免疫组织化学染色判断ER、PR和HER2表达情况.将钼靶X线表现中的肿瘤毛刺征、恶性钙化及肿瘤大小等与ER、PR和HER2表达状况进行比较研究.结果 70例中,ER表达阳性者39例(55.7%),PR表达阳性者37例(52.9%),HER2过表达者18例(25.7%).毛刺组HER2过表达率低于无毛刺组(15.9%对42.3%),差异有显著性(P=0.015).钙化组和无钙化组间ER、PR阳性率和HER2过表达率差异均无显著性.40～49岁组PR阳性率明显高于其他组(P=0.034).而ER、PR和HER2表达状况与肿瘤大小及患者月经状况之间无显著性相关.结论 我国女性浸润性乳腺癌患者的钼靶X线表现可在一定程度上反映ER、PR和HER2的表达状况.     

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.     

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。     

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.     

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.