不同年龄段乳腺癌临床病理特征分析

目的比较不同年龄段乳腺癌患者临床病理方面的特点,以探讨各年龄段之间的病理差异。方法将454例浸润性乳腺癌患者分为青年组（≤35岁）,中年组（36-59岁）,老年组（≥60岁）,比较不同年龄段患者的病理分期、淋巴结转移及雌、孕激素受体（ER、PR）表达等临床病理特点。结果3组乳腺癌的淋巴结转移率青年组明显高于中老年组,差异有显著性（P〈0.05）。病理分期青年组乳腺癌Ⅲ期病例明显高于中老年组,有统计学意义（P〈0.05）。在激素受体方面,青年组ER、PR阳性率明显低于中老年组,而Cer-b-2表达明显高于中老年组,差异有统计学意义（P〈0.05）。中年组和老年组间的各项观察指标比较差异无统计学意义。结论青年乳腺癌具有侵袭性强、生长快、恶性度高、易转移、病期晚的特点。     

Collagen remodelling in the guinea-pig uterine cervix at term is associated with a decrease in progesterone receptor expression

In human and guinea-pig parturition, progesterone withdrawal and estrogen action are not mediated by changes in their circulating levels. Instead, these events might be promoted by changes in the responsiveness of the uterus and cervix to progesterone and estrogen via changes in their receptors. In this study, the guinea-pig model was used to investigate whether high levels of progesterone and estrogen at term are associated with regional changes in PR and ERalpha levels in uterus and cervix. PR and ERalpha profiles were established in both subepithelium and the muscular layer of the cervix and the lower uterine horns during pregnancy, parturition and postpartum; while collagen remodelling was measured in the subepithelium. Our data showed that collagen remodelling involved in cervical ripening is temporally and spatially associated with a decrease in PR, whereas high expression of ERalpha is observed. This association was found in the subepithelium of the cervical tissue but not in the same region of the uterus. The muscular region of the cervix and uterus also present a transiently decreased expression of PR while ERalpha levels remain high. Thus, the present results indicate that, before parturition, diminished responsiveness of the cervix to progesterone might be caused by a decrease in PR levels and that this may be the mechanism of functional progesterone withdrawal. The guinea-pig was further validated as an animal model for human parturition studies.     

Premorbid body weight and its relations to primary tumour diameter in breast cancer patients; its dependence on estrogen and progesteron receptor status

Hormonal mechanisms have been offered as an explanation for the higher frequency of large tumours, lymph node metastases and poorer prognosis in obese breast cancer patients than in lean ones. If hormonal mechanisms are important for these relations, they should probably act more strongly in patients with hormonal receptor positive tumours than in those with negative ones. We have examined if the relations between premorbid body weight or Quetelet's index (weight/height²) and tumour diameter are modified by estrogen receptor alpha (ER) and progesteron receptor (PgR) status. The analyses were based on 1,241 women with unilateral disease treated with modified radical mastectomy living in the geografic area of Haukeland Hospital. Their body weight and height have been measured as a mean 12.5years before presentation of the disease. Body weight and Quetelet's index have been adjusted for age. The relations were studied using linear regression analyses adjusting the effect of body weight with height and mean nuclear area of the tumour cells and adjusting the effect of Quetelet's index for mean nuclear area. The main findings showed that patients with high body weight or Quetelet's index presented more often with PgR positive tumours than lean ones. Quetelet's index was also positively related to ER. These relations were present in patients older than 50 years of age (older). Patients with large tumours (>2.0cm) had significantly higher body weight and Quetelet's index than those with small ones. These differences were significantly present in older patients and in patients with PgR negative and ER negative – PgR negative tumours. Linear regression analyses confirmed that tumour diameter increases with body weight and Quetelet's index. These relations were present in both lymph node groups and in older patients. Stratification according to hormonal receptor status showed these relations to be significant in patients with ER negative, with PgR negative and those with ER negative – PgR negative tumours only. Taking age and hormonal receptor status into consideration simultaneously, both body weight and Quetelet's index were significantly related to tumour diameter in older patients with hormone receptor negative tumours. In conclusion body size was positively related to hormone receptor status and to diameter of the primary tumour. The relation to tumour diameter was present in older patients with hormone receptor negative tumours. Although hormonal mechanisms able to act on the tumour can not be excluded, mechanisms acting independent of hormonal receptors must be considered. Different mechanisms related to body fat cytokines are discussed.     

不同年龄乳腺癌的对比分析

目的　比较不同年龄阶段乳腺癌患者在临床及病理特征等方面的差别 ,以期探讨各年龄段之间的患病特点。方法　将 15 1例乳腺癌患者分为青年组 (≤ 3 5岁 ) ,中年组 ( 3 6～ 5 9岁 ) ,老年组 (≥ 60岁 )。比较不同年龄段患者的病程 ,肿瘤的大小、组织学类型、分级与分期、淋巴结转移及雌、孕激素受体 (ER、PR)表达等临床病理特点。结果　在ER、PR阳性率、病程方面 ,青年组和老年组明显低于中年组 (P <0 0 5 ) ;在肿瘤大小 ,组织学分级、TNM分期及淋巴结转移率方面 ,青年组明显高于中年组 (P <0 0 5 ) ,而老年组与青年组和中年组之间差异无显著性 (P >0 0 5 )。结论　青年人和老年人以非激素依赖性乳腺癌为主 ,病程短 ,而且青年人乳腺癌还具有生长快 ,恶性度高 ,转移早 ,病期晚的特点 ;中年人以激素依赖性乳腺癌多见 ,且病程长 ,恶性度低 ,转移晚 ,病期早。     

严重急性呼吸综合征患者血清性激素水平的测定和评价

目的　观察严重急性呼吸综合征 (SARS)患者性腺是否受到损害。方法　采用电化学发光免疫技术检测 6 6例男性SARS患者的血清雌二醇 (E2 )、孕酮 (PROG)、促卵泡激素(FSH)、黄体生成素 (LH)和催乳素 (PRL)水平 ,并与 40名健康对照者进行比较。结果　SARS患者血清E2、PROG含量明显低于对照组 (P <0 0 1) ,FSH、LH和PRL含量明显高于对照组(P <0 0 1)。重型SARS患者血清E2含量显著低于普通型。激素水平恢复要慢于临床症状的改善。结论　SARS患者中性激素含量异常 ,提示性激素水平改变有可能是SARS发病过程中的环节之一 ,SARS病程中性激素水平的恢复可能是一个缓慢的过程。     

Prognostic implications of lobular breast cancer histology: New insights from a single hospital cross-sectional study and SEER data

BackgroundInvasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC.MethodsPrimary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation.ResultsIn lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380–7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309–0.703), p = 0.0003) and BCSS (HR 0.441 (0.247–0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4–5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown).ConclusionThe prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority ( = node negative) of ILCs.     

Prognostic,predictive abilities and concordance of BCL2 and TP53 protein expression in primary breast cancers and axillary lymph-nodes: A retrospective analysis of the Belgian three arm study evaluating anthracycline vs CMF adjuvant chemotherapy

Given recent data on genetic heterogeneity within and individual’s tumor, we investigated if there were differences in the prognostic and predictive abilities of BCL2 and TP53 protein expression in primary breast cancer (TU) and corresponding axillary lymph-nodes (LN). We used patient samples from the adjuvant Belgian three-arm study which randomized between anthracycline containing regimens and traditional CMF. The endpoints analyzed were overall survival (OS), event-free survival (EFS) and interactions between chemotherapy regimens.At a median follow-up of 15.6 years, BCL2 and TP53 (in both TU and LN) were significantly associated with OS but only in the first 5 years. Likewise, BCL2 and TP53 (in both TU and LN) were associated with EFS in the first 2 years after randomization, with no association after 2 years. BCL2 and TP53 remained statistically significant after adjustment for the standard clinical–pathological characteristics in regard to OS and EFS in the respective first years after randomization, (p value < 0.001 for both markers).Furthermore, an interaction was found between high BCL2 expression in the TU (but not in LN) and benefit to CMF over anthracycline-based chemotherapy (interaction p value EFS: 0.042; OS = 0.01). No interaction was found for TP53 expression neither in TU nor in LN.We conclude that BCL2 and TP53 were predictive biomarkers for better and worse survival respectively, but only in the first two to five years after diagnosis. BCL2 expression in the TU but not in the LN was predictive of increased benefit to CMF vs anthracycline-based chemotherapy.     

雌、孕激素对去卵巢大鼠骨代谢及肾脏1,25-(OH)2D3受体mRNA表达的影响

目的:观察雌孕激素替代治疗对去卵巢大鼠骨组织计量学参数变化及大鼠肾脏1,25-(OH)2D3受体(VDR)mRNA 表达的影响,并探讨其可能的机制.方法:25只成年SD雌性大鼠,随机分为为5组,假手术组、单纯去势组以及去势 补充雌激素组、去势 补充孕激素组、去势 补充雌、孕激素组,每组5只.喂养3个半月后处死,取出肾脏,RT-PCR方法检测VDR mRNA的表达;取胫骨上段不脱钙骨制片,应用半自动图像数字化分析仪检测各组大鼠骨组织计量学参数.结果:与假手术组、雌激素及雌孕激素组相比,去卵巢大鼠松质骨骨量明显减少,伴有骨结构变差,骨形成和骨吸收的参数值增加(P<0.05);与去卵巢组相比,孕激素组大鼠无显著改变.去卵巢组大鼠肾脏VDR mRNA的相对表达量显著低于假手术组、雌激素组及雌孕激素组(P<0.05);而与孕激素组无显著差异.结论:雌激素能有效地抑制去卵巢大鼠的骨吸收和骨形成,降低骨转换,可能与促进去卵巢大鼠肾脏VDR mRNA的表达有关.     

COX-2在乳腺癌组织中的表达及其临床意义

目的探讨环氧化酶-2(COX-2)在乳腺癌组织中的表达及其临床意义。方法采用Elivision免疫组化技术,检测55例乳腺癌组织标本中COX-2的表达。结果55例乳腺癌组织中COX-2的阳性表达率为50.9%(28/55),其表达与患者的年龄、肿瘤大小、组织分级无关,雌激素受体(ER)、孕激素受体(PR)阴性组的阳性表达率明显高于ER、PR阳性组(P<0.05),其表达与淋巴结转移有关(P<0.01)。结论COX-2在乳腺癌中的表达明显上调,其与乳腺癌的发生、转移及预后均有密切关系,可以作为判断乳腺癌生物学行为的有用指标。