瘦素和瘦素受体在乳腺癌组织中的表达及其与临床预后的关系

目的　检测瘦素（ＯＢ）和瘦素受体（ＯｂＲ）在人乳腺癌组织中的表达情况,探讨二者与ＨＥＲ-２以及临床病理之间的关系,并分析它们对预后的影响。方法　用免疫组织化学的方法检测１１４例乳腺癌组织中ＯＢ和ＯｂＲ的表达,回顾分析相关的临床病理资料和随访情况。结果　ＯＢ和ＯｂＲ在大多数乳腺癌组织中均有表达,阳性率分别为７９.８％和８５.１％;ＯＢ和ＯｂＲ的表达与患者的年龄、绝经状态、肿瘤大小、肿瘤病理学分型、淋巴结转移及远处转移均无关（Ｐ＞０.０５）;与ＥＲ、ＰＲ、ｐ５３的表达状态也无关（P＞０.０５）;ＯｂＲ的表达与ＨＥＲ-２相关（P＝０.０１８）;ＯＢ阳性者的总生存时间（ＯＳ）短（Ｐ＝０.００９）;在亚组分析中,绝经后、三阴乳腺癌和淋巴结转移组中ＯＢ阳性的ＯＳ均短于ＯＢ阴性（P分别为０.０３８、０.００６和０.００４）。结论 ＯｂＲ与ＨＥＲ-２在乳腺癌中的表达具有相关性,ＯＢ可能是导致乳腺癌预后不良的因素。     

瘦素及瘦素受体与乳腺癌浸润、转移关系的研究

目的：了解瘦素及瘦素受体与乳腺癌浸润、转移关系。方法测量对比良性乳腺疾病与乳腺癌患者体重指数（body mass index,BMI）的差别;按腋窝淋巴结转移数由低到高分5组,S-P 方法检测不同分组中乳腺癌组织中瘦素及其受体的表达,ELASE 方法检测乳腺癌患者血清中瘦素的表达。结果良性乳腺疾病患者 BMI 为24．36±3．74,乳腺癌患者 BMI 为25．77±4．12,二者比较P＝0．028。瘦素在乳腺癌组织中的表达为：A 组163．87±16．33,B 组147．24±8．03,C 组133．54±18．82,D 组105．73±10．39,E 组81．52±8．72;乳腺癌组织中瘦素受体的表达为：A 组147．93±12．31,B 组125．03±16．15,C 组113．85±17．59,D 组107．25±12．85,E 组80．47±7．38;乳腺癌血清中瘦素的表达为：A组16．378±0．471,B 组21．393±1．551,C 组28．978±2．570,D 组35．706±2．942,E 组39．186±7．377。结论肥胖是乳腺癌发病的高危因素。瘦素及其受体在乳腺癌组织中的表达随淋巴结转移数增多而依次升高,提示瘦素及其受体促进乳腺癌的转移、复发。     

瘦素受体基因变异与乳腺癌发生的关系

目的 探讨瘦素受体基因(OB-R)第exon 4、6、9、20核苷酸位点变异与乳腺癌发生的关系.方法 采用体外基因扩增、测序的方法,检测155例乳腺癌患者肿瘤组织、56例乳腺良性病组织和100例健康人的抗凝血中OB-R基因核苷酸位点变异情况.结果 OB-R基因第exon 4在乳腺癌组、乳腺良性病组和健康对照组受检者中均未发生核苷酸位点变异,而第exon 9的1029核苷酸位点均发生了碱基置换,3组之间比较,差异无统计学意义(P=0.574).第exon 6的668核苷酸位点发生了碱基颠换,导致多态性Gln223Arg.Gln223Arg的GG、GA、AA基因型在乳腺癌组中的表达频率分别为70.9%、17.4%和12.3%,在乳腺良性病组中的表达频率分别为80.4%、14.3%和5.4%,在健康对照组中的表达频率分别为81.0%、16.0%和3.0%;G和A等位基因在乳腺癌组中的表达频率分别为79.1%和20.8%,在乳腺良性病组中的表达频率分别为87.5%和12.5%,在健康对照组中的表达频率分别为89.0%和11.0%.3组Gln223Arg基因型和等位基因表达频率比较,差异有统计学意义(x2=16.11,P＜0.005;x2=11.41,P＜0.01).第exor 20的3057核苷酸位点发生了碱基颠换,导致多态性Pro1019Pro.Pro1019Pro的GG、GA、AA基因型在乳腺癌组中的表达频率分别为11.6%、30.3%和56.1%,在乳腺良性病组中的表达频率分别为32.1%、44.0%和28.5%,在健康对照组中的表达频率分别为32.0%、45.0%和23.0%;G和A等位基因在乳腺癌组中的表达频率分别为26.8%和73.2%,在乳腺良性病组中的表达频率分别为51.8%和48.2%,在健康对照组中的表达频率分别为54.5%和45.5%.3组Pro1019Pro基因型和等位基因变异频率比较,差异有统计学意义(x2=6.56,P＜0.03;x2=5.45,P＜0.05).乳腺癌组超重和肥胖者第exon 6、exon 20发生碱基颠换的频率明显高于正常体重者,差异有统计学意义(P＜0.05,P＜0.01).结论 OB-R基因第exon9核苷酸位点变异与乳腺癌发生无关,而第exon 6和第exon 20核苷酸位点变异可能与乳腺癌的发生风险有关.

Abstract：

Objective The aim of this study was to investigate the relationship of the mutations of leptin receptor gene exon 4, exon 6, exon9, and exon20 with the tumorigenesis of breast cancer. Methods Genomic DNA was extracted from breast cancer tissues of 155 patients, benign lesions of 56 patients and normal tissues and blood samples from 100 health control subjects. The leptin receptor genes were assayed with polymerase chain reaction (PCR) amplification and direct sequence analysis. Results Nucleotide substitutions no mutations were found at exon 4, and nucleotide substitutions occurred at codon 1029 in exon 9, no significant difference among the three groups (P =0.574). The nucleotide substitutions at codon 668 in exon 6 resulted in Gln223Arg polymorphisms. The occurring frequencies of GG, GA, AA in breast cancer, breast benign lesions tissues and health tissues control group were 70.9% and 17.4%, 12.3%;80.4%, 14.3% and 5.4%; and 81.0%, 16.0%, and 3.0%, respectively. Alleles of G and A in the three groups were 79.1% and 20.8%, 87.5% and12.5%, and 89.0% and 11.0%, respectively. Compared the Gln223Arg genotype with the three allele groups, there were significant differences (x2 = 16. 11 ,P ＜0.005 and x2 = 11.41, P ＜ 0. 01 ), respectively. The nucleotide substitutions at codon 3057 in exon 20 resulted in Pro1019Pro polymorphisms. The occurrence frequencies of GG, GA, AA in the breast cancer,benign disease and health control groups were 11.6%, 30.3% and 56. 1%; 32.1%, 44.0% and 28.5%;and 32.0%, 45.0% And 23.0%, respectively. Alleles of G and A in the three groups were 26.8% and 73.2% ,51.8% and 48.2%, and 54.5% and 45.5%, respectively. There are significant differences among the three groups (x2 = 6.56, P ＜ 0. 03 and x2 = 5.45, P ＜ 0. 05 ), respectively. Nucleotide substitutions occurred at relatively high frequencies at exon 6 and exon 20 in obese and overweight breast cancer patients compared with those in normal weight breast cancer patients, there were significant differences ( P ＜ 0.05and P＜0.01). Conclusions Our findings show that there is no relationship between the variations of leptin receptor gene exon 9 and tumorigenesis of breast cancer. The variation rate of leptin receptor gene exon 6 and exon 20 are significantly increased in the obese and overweight breast cancer paztients.     

瘦素及瘦素受体与肿瘤

瘦素(LEP)是肥胖基因的表达产物，它与其受体结合可发挥生物学作用，是近几年来肥胖及相关疾病发病机制和防治研究的重点。现综述LEP及其受体在肿瘤发生发展过程中的研究进展。     

乳腺癌组织瘦素和瘦素受体表达及其临床意义的研究

目的:检测Leptin和Ob-R在乳腺癌中的表达,并探讨其临床意义.方法:用免疫组化的方法检测60例乳腺癌、30例乳腺良性病变及30例癌旁正常乳腺组织中Leptin和0b-R的表达.结果:乳腺癌Leptin和Ob-R表达与癌旁乳腺组织相比差异有统计学意义(P1=0.000;P2=0.000),乳腺癌Leptin和Ob-R表达与乳腺良性病变相比差异亦有统计学意义(P1=0.000;P2=0.000),而乳腺良性病变和癌旁乳腺组织相比差异均无统计学意义(P1=0.169;P2=0.545);乳腺癌中有淋巴结转移组Leptin和Ob-R表达与无淋巴结转移组相比,差异均有统计学意义(P=0.036);乳腺癌不同TNM分期与Leptin和Ob-R表达均呈正相关(P J=0.021,γ1=0.297;P2=0.007,γ2=0.342).结论:瘦素可以作为诊断乳腺癌、判断乳腺癌分期和预后的辅助手段,能够为乳腺癌治疗提供新的思路.     

瘦素和瘦素受体在肺癌组织中的表达

目的探讨瘦素及其受体在肺癌发生、发展中的作用。方法采用免疫组化S-P法检测68例肺癌组织、相应癌旁组织和正常肺组织中瘦素及其受体的表达。结果瘦素及其受体在肺癌组织中的表达率分别为72.06%(49/68)、64.71%(44/68),相应癌旁组织分别为42.65%(29/68)、33.83%(23/68),正常肺组织分别为26.47%(18/68)、29.41%(20/68)。瘦素及其受体在肺癌组织的表达高于相应癌旁组织及正常肺组织(P<0.05)。在肺癌组织中瘦素与瘦素受体的表达呈正相关关系(r=0.754,P<0.01)。结论瘦素及其受体的表达在肺癌的发生、发展中起一定的促进作用。     

瘦素及瘦素受体与肿瘤

瘦素(LEP)是肥胖基因的表达产物,它与其受体结合可发挥生物学作用,是近几年来肥胖及相关疾病发病机制和防治研究的重点.现综述LEP及其受体在肿瘤发生发展过程中的研究进展.     

212例乳腺癌雌激素受体水平与临床病理的关系分析

２１２例乳腺癌雌激素受体水平与临床病理的关系分析曹飞麟，周涛，方志沂，丁秀敏浙江省台州医院（台州市３１７０００）乳腺癌的治疗和预后与乳腺癌组织中的雌激素受体（ＥＲ）水平有密切关系。现收集浙江省台州医院和天津市肿瘤医院１９８６年１月至１９８７年１２月经...     

人乳腺癌雌激素受体和孕酮受体与外周血性激素水平的关系

测定了30例未绝经和73例的绝经后乳腺癌妇女的雌激素受体(ER)、孕酮受体(PR)和外周血雌酮(E_1)、雌二醇(E_2)、孕酮(P)和睾酮(T)水平。结果表明:(1)乳腺癌病人外周血E_1和P水平在ER_ 组和ER PR-组明显高于ER-组和ER-PR-组(P<0.05)。(2)乳腺癌病人外周血E_2水平在PR 组和ER~ PR~ 组明显高于PR-组和ER-PR-组(3)乳腺癌病人术后生存期与外周血T水平有关,ER-组和PR-组乳腺癌病人中,术后生存期≥5年组和术后生存期<5年组之间外周血T水平有显著差异(P<0.05,P<0.001)。     

血清瘦素水平及体质指数与乳腺癌发生的相关性研究

  目的 探讨血清瘦素水平及体质指数与乳腺癌发生的相关性，为乳腺癌的防治寻找科学依据。方法 收集术前乳腺癌患者90例，乳腺良性疾病患者32例，健康对照103例血清，采用放射免疫分析法测定瘦素水平，并进行体质指数的测量与计算。采用SPSS软件包进行统计学处理。结果 乳腺癌组血清瘦素水平与体质指数明显高于乳腺良性疾病和健康对照组，差异均具有统计学意义（P＜0.01）；三组人群瘦素水平与体质指数均呈正相关，相关系数分别为0.327（P＜0.001），0.416（P＜0.001），0.525（P＜0.001）；Logistic回归分析，血清瘦素水平的升高是乳腺癌发生的危险因素，OR值为1.14（95 %CI：1.076 ~ 1.209）。结论 血清瘦素水平、体质指数升高可能与乳腺癌发生有关。     

Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea

Leptin plays an important role in the regulation of body fat homeostasis, and potential associations of leptin receptor gene (LEPR) polymorphisms with obesity have been suggested. Obesity is considered to relate to breast cancer. We assessed the role of leptin in relation to breast cancer. We measured the serum leptin concentrations of 45 Korean pre-treatment patients with breast cancer and 45 age-matched controls. By direct sequencing, we investigated four leptin receptor gene (LEPR) polymorphisms at codons 109, 223, 656, and 1019. There was no significant difference between the mean leptin concentrations of the patient and control groups in both pre- and post-menopausal women. The frequencies of the wild-type for LEPR codons 109, 223, and 1019 were very low. No increased risk estimate was found for the four LEPR polymorphisms. Our results indicate that it is difficult to explain breast cancer on the basis of serum leptin concentrations or polymorphisms in the LEPR gene.     

８６９例乳腺癌临床病理特征分析

目的　分析乳腺癌的临床病理特征,以提高临床诊治水平。方法　回顾性分析２００１年１月至２００９年１月我院收治的８６９例乳腺癌患者临床资料,采用免疫组化ＳＰ法检测激素受体状况,结合临床病理特征进行分析。结果　４０～４９岁和５０～５９岁两组病例所占百分比最高,分别为３１.１％和２４.７％。组织学类型以浸润性非特殊型癌最多,占８０.２％（６９７／８６９）。诊断时Ⅰ ～Ⅱ期占８０.１％（６９６／８６９）,其中发病时无淋巴结转移者占６０４％。本组ＥＲ阳性者占６６９％（５８１／８６９）,ＰＲ阳性者占６９.５％（６０４／８６９）,ＨＥＲ-２阳性者占３９.７％（３４５／８６９）。ＥＲ、ＰＲ表达与发病年龄呈明显正相关（Ｐ＜０.０５）,ＨＥＲ-２表达与乳腺癌发病年龄无相关性（Ｐ＞０.０５）。结论　乳腺癌患病年龄较以往提前,早期乳腺癌可行保乳手术,受体阳性患者比例高,可采用内分泌治疗。     

Serum adiponectin and leptin levels in Taiwanese breast cancer patients

The role of two adipocytokines, adiponectin and leptin, in Taiwanese breast cancer patients remains to be determined. In this study, we analyzed the correlations between the serum levels of adiponectin and leptin and the various clinicopathological parameters in 100 newly diagnosed, histologically confirmed breast cancer patients and 100 controls. We found serum levels were decreased significantly for adiponectin in the breast cancer patients, in comparison to controls (Student t-test, P=0.003), while serum levels were increased significantly for leptin in the breast cancer patients in comparison to controls (Student t-test, P=0.025). Leptin/adiponectin (L/A ratio) were increased significantly in the breast cancer patients, in comparison to controls (Student t-test, P=0.009). Among the clinicopathological parameters, estrogen receptor, progesterone receptor, HER2/neu, lymph node metastasis, tumor stage, and tumor grade all showed no effect on the serum levels of adiponectin and leptin. BMI was negatively and positively correlated to serum adiponectin and leptin levels, respectively (Spearman's correlation, r=-0.333 and 0.323, respectively; P<0.001 for both). Intriguingly, serum L/A ratio disclosed a positive correlation to tumor size (r=0.21, P=0.036). In summary, our results suggest that low serum adiponectin levels and high serum leptin levels are associated with an increased risk for breast cancer. Also, independent of the effect of BMI, the increased serum ratio of L/A may indicate the presence of aggressive breast cancers.     

Molecular mechanisms of leptin and adiponectin in breast cancer

Obesity is associated with an increased risk of breast cancer in postmenopausal women. Accumulating evidence suggests that adipose tissue, which is an endocrine organ producing a large range of factors, may interfere with breast cancer development. Leptin and adiponectin are two major adipocyte-secreted hormones. The pro-carcinogenic effect of leptin and conversely, the anti-carcinogenic effect of adiponectin result from two main mechanisms: a modulation in the signalling pathways involved in proliferation process and a subtle regulation of the apoptotic response. This review provides insight into recent findings on the molecular mechanisms of leptin and adiponectin in mammary tumours, and discusses the potential interplay between these two adipokines in breast cancer.     

Relationship between the expressions of survivin and the prognostic related factors in breast cancer

Objective： To study the relationship between the Survivin expression and the histological grade, status of ER, expression of PS2 and the prognosis of patients with primary invasive breast cancer. Method： By using LSAB and SP immunohistochemical method, the expression of Survivin, PS2 and ER in 95 cases of invasive breast cancer were detected. Results： the positive rate of Survivin was 70.5% （67/95） and the expression of Survivin was positively related to the histological grade and status of PS2 and ER. The survival time after operation of patients without expression of Survivin was longer than those with positive Survivin. Conclusion： These data suggest that Survivin expression may be considered as a new unfavorable prognostic factor of breast cancer.     

Associations between polymorphisms in leptin and leptin receptor genes and colorectal cancer survival

Objective:Leptin(LEP) is an obesity-associated adipokine associated with tumor cell growth. We examined the relevance of genetic variants of LEP and leptin receptor(LEPR) to colorectal cancer(CRC) survival by using data from the Newfoundland Familial Colorectal Cancer Study.Methods:A total of 532 patients newly diagnosed with CRC between 1997 and 2003 were followed up until April 2010. Data on their demographics and lifestyles were collected via questionnaires. Genotyping of blood samples was pe...     

新疆维吾尔族女性乳腺癌临床病理特点与预后分析

 目的 探讨新疆地区维吾尔族女性乳腺癌的发病特点、临床与病理特征及其与预后的关系。方法 对74例有完整病例资料及随访的维吾尔族女性乳腺癌患者的临床病理资料进行多因素COX回归分析。结果 74例女性维吾尔族乳腺癌3年生存率和5年生存率分别为 75.00 %（48／64）和43.50 %（20／46），经多因素COX回归分析显示，年龄、月经状况、淋巴结转移、TNM分期及PR表达5项指标反应维吾尔族女性乳腺癌的预后情况，危险度分别为0.037，0.103，13.851，18.877和0.046。结论 新疆维吾尔族女性乳腺癌患病的比重小，但发病年龄较早，以36～50岁多见，且以Ⅱ，Ⅲ期居多，预后较差。年龄、月经状况、淋巴结转移、TNM分期、PR表达是影响维吾尔族女性乳腺癌预后的独立指标。早诊断、早治疗是提高其生存率的关键。