PTEN基因单核苷酸多态性与乳腺癌的关系

目的:研究PTEN基因-9C/G单核苷酸多态性与中国汉族女性人群乳腺癌之间的相关性。方法:采用基于人群的病例-对照研究,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行基因分型,检测210例中国汉族女性乳腺癌患者和210例健康女性的PTEN基因-9C/G多态性。结果:PTEN基因-9C/G位点(rs11202592)多态性基因型分布频率在两组间比较无显著性差异(P=0.862)。PTEN基因-9C/G单核甘酸多态性不同基因型间在ER、Her-2表达上无显著性差异(P>0.05)。结论:PTEN基因-9C/G位点多态性与中国汉族女性乳腺癌易感性无明显关联,ER、HER-2表达同此位点多态性也无明显关联。     

PTEN的研究进展及与乳腺癌的关系

PTEN是 1997年发现的具有双重特异性磷酸酶活性的抑癌基因 ,该基因的变异与人类多种肿瘤的发生发展及预后有关。本研究就PTEN的研究进展及其与乳腺癌的关系进行了综述     

ATM haplotypes and breast cancer risk in Jewish high-risk women

While genetic factors clearly play a role in conferring breast cancer risk, the contribution of ATM gene mutations to breast cancer is still unsettled. To shed light on this issue, ATM haplotypes were constructed using eight SNPs spanning the ATM gene region (142 kb) in ethnically diverse non-Ashkenazi Jewish controls (n=118) and high-risk (n=142) women. Of the 28 haplotypes noted, four were encountered in frequencies of 5% or more and accounted for 85% of all haplotypes. Subsequently, ATM haplotyping of high-risk, non-Ashkenazi Jews was performed on 66 women with breast cancer and 76 asymptomatic. One SNP (rs228589) was significantly more prevalent among breast cancer cases compared with controls (P=4 x 10(-9)), and one discriminative ATM haplotype was significantly more prevalent among breast cancer cases (33.3%) compared with controls (3.8%), (P< or =10(-10)). There was no significant difference in the SNP and haplotype distribution between asymptomatic high-risk and symptomatic women as a function of disease status. We conclude that a specific ATM SNP and a specific haplotype are associated with increased breast cancer risk in high-risk non-Ashkenazi Jews.     

Passive coping and psychological distress in women adhering to regular breast cancer surveillance

Since 2000 the MRISC study evaluates the psychological consequences of regular breast cancer surveillance for women at increased risk for hereditary breast cancer. Coping style may influence these psychological consequences. In a cohort of 357 women at increased risk for hereditary breast cancer, the impact of coping styles on the course, divided into level and trend of psychological distress (general and breast cancer specific) was examined, around two consecutive surveillance appointments. With structural equation modelling we found passive coping to be associated with higher levels of both general and breast cancer specific distress. Seeking social support, expression of emotions and thinking comforting thoughts were associated with lower levels of psychological distress. Coping style was not associated with the trend of psychological distress around the two surveillance appointments. It is recommendable to take coping styles into account when counselling these high-risk women.     

High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study

High-risk human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis. Based on this hypothesis, we recently studied the effect of E6/E7 onco-proteins of high-risk HPV type 16 in two non-invasive human breast cancer cell lines, BT20 and MCF7; we reported that E6/E7 converts these cell lines to invasive cells. This is accompanied by an overexpression of Id-1, which is an important regulator of breast metastasis. In this investigation, we examined the presence of high-risk HPVs (16, 18, 31, 33 and 35) and the expression of their E6 onco-protein as well as their correlation with Id-1 gene expression, using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis, respectively, in a cohort of 113 Syrian breast cancer patients. We found that high-risk HPV types 16, 18, 31, 33 and 35 are present in 8.84, 9.73, 7.07, 55.75 and 37.16% of our samples, respectively, which represent invasive breast cancers. Overall, 69 (61.06%) of the 113 samples are HPV positive; among these specimens 24 tissues (34.78%) are coinfected with more than one HPV type. Furthermore, we report that the expression of the E6 onco-protein of these high-risk HPVs is correlated with Id-1 overexpression in the majority of invasive breast cancer tissue samples. Our data suggest that high-risk HPV infections are associated with human breast cancer progression in Syrian women.     

PTEN在乳腺癌及癌前病变中的表达及意义

目的：探讨人第10号染色体缺失的磷酸酶（phosphatase and tensin homolog deleted on chromosometen, PTEN）在乳腺导管上皮不典型增生（ atypical ductal hyperplasia,ADH）、导管内癌（ ductal carcinoma in situ, DCIS）、浸润性导管癌（invasiveductal carcinoma,IDC）三组病变组织中的表达及意义。方法：收集 ADH 60例、DCIS 100例、IDC 165例,利用 Real - time RT - PCR 检测 ADH、DCIS、IDC 病变组织中 PTEN 基因在 mRNA 水平的表达情况;利用 Western - Blot 方法和免疫组织化学技术检测 ADH、DCIS、IDC 病变组织中 PTEN 蛋白的表达情况。结果：Real - time RT - PCR 技术结果显示,ADH 组 PTEN mRNA 表达水平最高,DCIS 组次之,IDC组最低差异具有统计学意义（t =26.661,P <0.05）。Western - Blot 技术检测 PTEN 蛋白在 ADH、DCIS、IDC 三组病变组织中的表达呈逐渐下降趋势,差异具有统计学意义（t =9.355,P <0.05）。免疫组织化学检测 PTEN蛋白在 ADH、DCIS、IDC 三组病变组织中的阳性表达率分别为91.9%、51.0%、36.9%,差异有统计学意义（χ2=54.734,P <0.05）。分析 PTEN 蛋白表达水平与乳腺癌患者临床资料的相关性,结果显示其与患者年龄无相关性（P >0.05）,而与患者的肿瘤分化程度、临床分级及转移有相关性,且差异有统计学意义（χ2=15.8,P <0.05）。结论：无论是在蛋白水平还是 mRNA 水平,PTEN 基因的表达从 ADH 到 DCIS 再到 IDC 呈下降趋势,提示 PTEN 可能参与了乳腺癌发生发展的过程,为日后治疗提供靶点理论依据。     

Genetic changes in the PTEN gene and their association with breast cancer in Pakistan

The PTEN gene, a candidate tumor suppressor, is one of the more commonly inactivated and extensively studied genes in cancer. However, few data are available about the role of germ line mutations of this gene in sporadic breast cancer cases. The purpose of this study was to determine extent of involvement of this gene in breast cancer in Pakistan. To test the hypothesis that genetic variations of PTEN play a role in the etiology of breast cancer, a population based case-control study was conducted in 350 breast cancer patients along 400 healthy controls. After extracting DNA from blood, the whole coding sequence of PTEN along with intron/exon boundaries was genotyped by polymerase chain reaction-single stranded conformational polymorphism. Sequencing analysis revealed nineteen different types of mutations in different regions of PTEN (in exon 2, 4, 5, 6, 7 and splicing sites of intron 2 and 4 and also in the 3' UTR region), including 3 silent, 8 missense, 2 frame shift and 6 splice site variations. Among the observed variations in this study, three missense mutations have already been reported i.e. 319G>A (Asp106Asn), 389G>A (Arg129Gln) and 482G>A (Arg160Lys) in different populations. The present results suggest that a wide range of germline PTEN mutations may play a role in the pathogenesis of breast cancer.     

The multimorbidity profile of South African women newly diagnosed with breast cancer

Multimorbidity in women with breast cancer may delay presentation, affect treatment decisions and outcomes. We described the multimorbidity profile of women with breast cancer, its determinants, associations with stage at diagnosis and treatments received. We collected self-reported data on five chronic conditions (hypertension, diabetes, cerebrovascular diseases, asthma/chronic obstructive pulmonary disease, tuberculosis), determined obesity using body mass index (BMI) and tested HIV status, in women newly diagnosed with breast cancer between January 2016 and April 2018 in five public hospitals in South Africa. We identified determinants of ≥2 of the seven above-mentioned conditions (defined as multimorbidity), multimorbidity itself with stage at diagnosis (advanced [III–IV] vs. early [0–II]) and multimorbidity with treatment modalities received. Among 2,281 women, 1,001 (44%) presented with multimorbidity. Obesity (52.8%), hypertension (41.3%), HIV (22.0%) and diabetes (13.7%) were the chronic conditions that occurred most frequently. Multimorbidity was more common with older age (OR = 1.02; 95% CI 1.01–1.03) and higher household socioeconomic status (HSES) (OR = 1.06; 95% CI 1.00–1.13). Multimorbidity was not associated with advanced-stage breast cancer at diagnosis, but for self-reported hypertension there was less likelihood of being diagnosed with advanced-stage disease in the adjusted model (OR 0.80; 95% CI 0.64–0.98). Multimorbidity was associated with first treatment received in those with early-stage disease, p = 0.003. The prevalence of multimorbidity is high among patients with breast cancer. Our findings suggest that multimorbidity had a significant impact on treatment received in those with early-stage disease. There is need to understand the impact of multimorbidity on breast cancer outcomes.     

超声联合弹性成像在非哺乳期乳腺癌诊断中的应用价值分析

目的：研究超声联合弹性成像在非哺乳期乳腺癌诊断中的应用价值。方法选择105例乳腺病灶患者,按照术后病理或超声引导穿刺结果分为乳腺癌组（41例）与乳腺炎组（64例）,两组均行超声、弹性成像检查,观察两组患者病灶影像学特征。结果两组患者共检出良性病灶68个,恶性病灶79个。良性病灶检出率最高为慢性乳腺炎（45.59%）,恶性病灶中检出率最高的为浸润性导管癌（75.95%）。良性病灶多数未见微小钙化,钙化病灶内部呈小条状或斑点状回声,多数病灶后方回声未见明显衰减。恶性病灶多呈微小钙化,钙化病灶内多呈簇状或散在点状强回声,病灶后方回声多明显衰减,良、恶性病灶微小钙化及后方回声衰减情况检出率有统计学差异（P﹤0.05）。恶性病灶内部Ⅱ～Ⅲ级血流比例（82.28%）多于良性病灶（58.82%）,差异有统计学意义（P﹤0.05）。恶性病灶血流多呈不规则穿入型血流信号,良性病灶周围血流信号程度不等。良性病灶弹性成像4～5分为20.59%,恶性病灶为91.14%,差异有统计学意义（P﹤0.05）。良性病灶RI≥0.70为26.47%,恶性病灶RI≥0.70为74.68%,差异有统计学意义（P﹤0.05）。常规超声恶性病灶诊断率（67.09%）低于常规超声联合弹性成像（86.08%）,差异有统计学意义（P﹤0.05）。结论超声联合弹性成像在诊断乳腺良恶性病变上较单纯超声更具优势。     

115例临床未触及肿块的乳腺癌诊断分析

背景与目的：早期诊断是提高乳腺癌治疗疗效的关键,乳腺癌病理分期越早,临床症状越不典型,本研究回顾性分析了临床体检未触及肿块（包括乳房及腋淋巴结均未触及肿块）乳腺癌诊断的方法与特点,以期提高乳腺癌的早期诊断率。方法：收集2006年9月—2009年3月期间收治的共115例体检未触及肿块的乳腺癌患者的临床检查资料,包括乳头溢液、钼靶X线片、超声检查的情况,并分析其病理特征及肿瘤分期情况。结果：115例患者（117侧乳房）中,原位癌（包括导管原位癌、导管上皮内肿瘤、小叶原位癌、神经内分泌性导管内癌、大汗腺性导管内癌）占33.3%,微小浸润性导管癌占22.2%,浸润性癌占44.5%。20例（22侧）单纯乳头溢液患者原位癌11侧,占50%;微小浸润导管癌3侧,占13.6%;浸润性癌8例（包括浸润性导管癌7例,粘液腺癌1例）,占36.4%。34例单纯钼靶表现异常者中原位癌（15例）和微小浸润导管癌（11例）共占76.5%。浸润性癌占23.5%;19例单纯表现为B超结节者中原位癌占31.6%,浸润性导管癌比例高达68.4%。乳头溢液伴钙化灶者,原位癌占50.0%;乳头溢液伴B超结节者,原位癌占33.3%;B超结节伴钙化灶,以及乳头溢液伴B超结节与钙化灶者,原位癌均占50.0%。术后病理分期情况,0～Ⅰ期96例（98侧）占83.8%,Ⅱ期15例,Ⅲ期4例;腋淋巴结转移1～3枚的11例,4～9枚的3例,〉10枚的1例。结论：乳房体检乳腺未触及肿块时,要重视B超、钼靶等影像学检查及乳头溢液的临床检查,其中一项异常,应积极进一步诊治。     

Stage of breast cancer at diagnosis among women with cosmetic breast implants

Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found.     

早期乳腺癌诊断的临床分析

目的：探讨早期乳腺癌的临床诊断方法。方法：对482例乳腺癌患者的诊治过程进行回顾性分析。结果：乳腺钼靶与彩超联合检查易发现早期乳癌。结论：乳腺普查可以发现无临床症状的早期乳癌患者。     

PTEN在乳腺浸润性导管癌中的表达及其与预后的关系

目的:研究抑癌基因PTEN在乳腺浸润性导管癌中的表达及其临床意义。方法:采用免疫组化技术(S蛳P)检测50例原发性乳腺浸润性导管癌中PTEN的表达情况。结果:PTEN总的表达缺失率为44 %(22/50)。PTEN表达缺失率随着肿瘤大小、组织学分级和临床分期的增高而升高(P<0.05)。生存时间在10 a以上病例的PTEN表达缺失率显著低于生存时间不足5 a组和5 a～10 a组(P<0.05)。有腋淋巴结转移组和无腋淋巴结转移组的PTEN表达缺失率分别为58.3 %和30.8 %,但统计学分析差异无显著性(P=0.05)。PTEN表达与ER状态关系不大,但两者联合检测可能对临床评估预后更有意义。结论:检测乳腺浸润性导管癌PTEN在蛋白水平的表达缺失状况可能有助于对其预后的判断。     

Forty-year trends in menopausal hormone therapy use and breast cancer incidence among postmenopausal black and white women

After reports from the Women's Health Initiative randomized trial evaluating estrogen plus progestin, there was a sudden, substantial, and sustained decrease in all categories of menopausal hormone therapy, and the first reduction in age-adjusted breast cancer incidence in more than 20 years was seen in 2003-2004 among US women 50 years of age or older. Subsequent trends in breast cancer incidence have been described, but most reports have not focused on the postmenopausal age group or fully engaged the potential influence of reduced hormone therapy on breast cancer incidence trends by race/ethnicity. To address this gap, this commentary examines trends for annual age-adjusted breast cancer incidence over a 40-year period from 1975 to 2015 for white and black women on the basis of findings from the Surveillance, Epidemiology, and End Results 9 registries. Overall, the sharp decline in breast cancer incidence seen in 2003-2004 was followed in the subsequent decade by a continued low breast cancer incidence plateau in white women that has largely persisted. In contrast, a new discordance between breast cancer incidence trends in black and white women has emerged. In the 2005-2015 decade, a sustained increase in breast cancer incidence in black women has resulted in annual incidence rates comparable, for the first time, to those in white women. This commentary explores the hypothesis that the over-decade-long and discordant changes in breast cancer incidence rates in postmenopausal black and white women are, to a large extent, associated with changes in hormone therapy use in these 2 groups.     

乳腺癌组织中核转录因子NF—κB和抑癌基因PTEN的表达及其意义

目的：探讨乳腺癌中核转录因子NF—κB和抑癌基因PTEN的表达及意义。方法：用免疫组织化学方法检测58例乳腺癌、20例乳腺增生症组织中NF—κB和抑癌基因PTEN的表达。结果：乳腺癌中NF—κB表达明显高于乳腺增生症组织，NF—κB表达强度与组织学分级和腋淋巴结转移有关（P〈0．05）。与患者年龄、肿瘤大小、组织学分型无关。乳腺癌中PTEN蛋白阳性率低于乳腺增生症组织，乳腺癌PTEN蛋白的表达与乳腺癌组织学分级有关（P〈0．05），与患者年龄、肿瘤大小、组织学分型、腋淋巴结无明显相关性（P〉0．05）。NF—κB p65与PTEN蛋白在乳腺癌组织中表达呈负相关（r=-0．355，P〈0．05）。结论：提示乳腺癌中NF—κB的高表达及PTEN缺失表达与乳腺癌的发生发展有关。     

Recommendations for the surveillance of young women at increased risk for breast cancer

A review of the published reports regarding screening for breast cancer in young, at‐risk women has been undertaken. Draft recommendations for surveillance of these women with imaging methods such as mammography, ultrasound and MRI have been made.     

抑癌基因PTEN、PI3K、AKT在肺癌中的表达及临床意义

目的：探讨抑癌基因PTEN、PI3K、AKT在肺癌中的表达及临床病理学意义研究。方法采用免疫组化SP法检测PTEN、PI3K和AKT蛋白在62例肺癌组织和30例癌旁肺组织中的表达情况,并分析两者的相关性及与临床病理特征的关系,探讨其在肺癌中的作用机制。结果 PTEN mRNA在肺癌组织中表达明显低于癌旁组织,但PI3K mRNA和AKT mRNA在肺癌组织中表达则高于癌旁组织,差异均有统计学意义（P＜0．05）。 PTEN在肺癌组织中的阳性表达率为48．39％（30/62）,明显低于癌旁组织,而PI3K和AKT在肺癌组织中的阳性表达率分别为79．03％（49/62）和70．97％（44/62）,明显高于癌旁组织,差异具有统计学意义（ P＜0．01）。 PTEN、PI3K表达与肺癌的分化程度、TNM分期、淋巴结转移及病理类型相关,而AKT表达与肺癌的TNM分期、淋巴结转移及病理类型相关（ P＜0．05）。 PI3K与AKT表达呈正相关（P＜0．05）,与PTEN表达呈负相关（P＜0．05）,AKT与PTEN表达呈负相关（P＜0．05）。结论抑癌基因PTEN在肺癌中的低表达和PI3K/AKT的高表达,提示了PTEN、PI3K及AKT可能促进了肺癌的发生、发展及转移,而PI3 K/AKT细胞信号通路在此过程中起重要作用,可为肺癌的基因靶向治疗提供一个新的方向。     

乳腺癌组织中PTEN和p27kip1蛋白的表达及其相互关系

目的:探讨PTEN和p27kip1在乳腺癌组织中的表达规律及其相互关系。方法:采用免疫组化SP法检测64例乳腺癌组织中PTEN和p27kip1蛋白的表达。结果:乳腺癌组织PTEN(34/64)和p27kip1(33/64)蛋白表达显著低于正常乳腺组织(15/15),P值分别为0·0082和0·0078。有腋淋巴结转移、远处转移及ER阴性组PTEN表达分别为13/33、3/11和16/38,明显低于无腋淋巴结转移(21/31)、无远处转移(31/53)和ER阳性组(18/26),P值分别为0·0240、0·0063和0·03475。p27kip1在乳腺癌有腋淋巴结转移、远处转移及ER阴性组的表达分别为7/33、2/11和8/38,明显低于无腋淋巴结转移(15/31)、无远处转移(20/53)和ER阳性组(14/26),P值分别为0·0230、0·0440和0·0071。两者表达均与肿瘤大小无关。两种蛋白表达水平具有显著的相关性,P=0·0041。结论:PTEN、p27kip1表达异常与乳腺癌转移及恶性程度密切相关,两种基因蛋白表达强度一致,显示其在乳腺癌演进中具有协同作用。     

早期乳腺癌的诊断体会

目的　探讨发现早期乳腺癌的方法。方法　对 1997年至 1999年我院收治的 192例乳腺癌 ,进行回顾性研究。结果　其中早期乳癌 10例 ,占同期收治乳癌总数的 5 .2 %( 10 /192 )。其中T0癌 4例 ,肿块 <0 .5cm的微小癌 6例 ,有乳腺癌易患因素者 5例 ,有乳头溢液者 3例 ,有乳房局灶增厚者 1例 ,伴乳腺增生症者 3例 ,3例是在例行健康检查时发现的。结论　 ( 1)提高对早期乳腺癌的认识 ,“乳腺癌≠乳腺肿块” ;( 2 )普及防癌知识 ,提倡健康检查 ;( 3)重视早期乳腺癌的临床特点 ;( 4 )提倡多种诊断方法联合应用 ,取长补短 ,综合分析。     

Use of oral contraceptives and risk of breast cancer in young women

Many studies have shown that oral contraceptive (OC) use increases a young woman's risk of breast cancer, although some studies suggest that the risk may be limited to recent use. The objective of this study was to determine what particular aspects of OC use could be important for breast cancer development at an early age in the cohort of women who had the opportunity to use OCs all of their reproductive life. The cases were first diagnosed with breast cancer at age 40 or younger between 1983 and 1988, and identified by the Los Angeles County Cancer Surveillance Program. Control subjects were individually matched to participating cases on birth date (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Detailed OC histories were obtained during in-person interviews with subjects. In general the risk estimates were small, and not statistically significant. Compared to no use, having used OCs for 12 years or more was associated with a modest non-significant elevated breast cancer risk with an odds ratio (OR) of 1.4 (95% confidence interval (CI)=0.8–2.4). Long-term (12 years or more) users of high-dose estrogen pills had a non-significant 60% higher breast cancer risk than never users (CI=0.9–3.2). Early use was associated with slightly higher ORs among young women (age 35), and among parous women. Recent use was associated with somewhat higher ORs among parous women and women above age 36. Analyses by stage, body weight, and family history yielded similar results. This study is consistent with a modest effect of early OC use on breast cancer risk in young women.