A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast Cancer

Background and objectives In breast cancer, the expression pattern of CXCR4 may be correlated with the degree of axillary lymph node involvement. The aim of this study was to evaluate the contributing factors that contribute to the correlation between CXCR4 expression and axillary lymph node metastasis in breast cancer. Methods Between August 1997 and August 2002, sections of paraffin-embedded tissue were obtained from 107 patients who received optimal treatment for breast cancer. The expression of CXCR4 was evaluated by immunohistochemical staining. Results A significant correlation was found in the expression of nuclear CXCR4 and lymph node metastasis (P = 0.03). We found a significant correlation between a high nuclear expression of CXCR4 and axillary lymphatic metastasis in estrogen and progesterone receptor negative breast cancer (P = 0.01 and P = 0.01). There was a significant correlation between the high expression of nuclear CXCR4 and axillary lymphatic metastasis in comparisons between positive estrogen and/or progesterone receptor expression and negative expression (P = 0.02). Conclusions Our results showed that high expression of nuclear CXCR4 was significantly correlated with lymph node metastasis in breast cancer. The high expression of nuclear CXCR4 in hormone receptor negative breast cancer was associated with a high possibility of lymph node metastasis.     

单激素受体阳性乳腺癌的临床特点及预后研究

目的探讨单激素受体阳性乳腺癌的临床病理及预后特点。方法选取2000年1月-2004年12月就诊的Ⅰ~Ⅲ期乳腺癌568例,其中雌激素受体（estrogen receptor,ER）单阳型乳腺癌80例和孕激素受体（progesterone receptor,PR）单阳型乳腺癌58例（共138例）,分析两组单激素受体乳腺癌的临床病理特征及预后特点。结果 PR单阳型组年龄≤50岁以及绝经前患者比例显著高于ER单阳型组（P〈0.05）;ER及PR单阳型乳腺癌的无病生存期（disease-free survival,DFS）、总生存期（oerall survival,OS）差异无统计学意义（P〉0.05）;ER单阳型组的DFS、OS明显优于双阴型乳腺癌（P〈0.05）,但PR单阳型组与其差异无统计学意义（P〉0.05）;PR单阳型组的DFS及OS较双阳型乳腺癌显著缩短（P〈0.05）,而ER单阳型组与其差异无统计学意义（P〉0.05）。结论 PR单阳型乳腺癌更多见于年轻、绝经前女性,与ER单阳型乳腺癌的生存期差异无统计学意义;PR单阳型乳腺癌的预后接近于双阴型乳腺癌,而ER单阳型乳腺癌则更接近于双阳型乳腺癌。     

乳腺纤维囊性病性激素周期节律的变化

测定133例乳腺纤维囊性病(FCD)和17例正常人卵泡期、排卵期、黄体期、月经前期血和尿雌二醇(E_2)和孕酮(P)。根据性激素分泌类型不同分为5型:A型54例,E_2和P分泌峰提前出现,P分泌时相延长,E_2在排卵期分泌显著降低;B型16例,P分泌正常。但排卵期E_2浓变显著降低;C型16例,排卯期E_2分泌降低,黄体期出现P分泌峰,但其分泌延迟至月经前期,同时伴有E_2浓度增加;D型41例,虽然排卵期E_2和黄体期P分泌正常,但E_2和P分泌延迟消失,在月经前期均未能回复到正常;E型6例,没有P分泌,血尿E_2含量在月经周期中均处于低水平。对各型FCD患者与正常人血、尿E_2平均数进行比较,表明FCD的共同特点是卵泡期和月经前期血清E_2浓度增加和排卵期E_2浓度降低。     

Mixed-Micellar Proliposomal Systems for Enhanced Oral Delivery of Progesterone

The objective of our study was to develop a mixed-micellar proliposomal formulation of poorly water-soluble drug progesterone and evaluate the dissolution profile and membrane transport. Several formulations of proliposomes were prepared by mixing different concentrations of lipid, progesterone, polysorbate 80, and microcrystalline cellulose. The mixed-micellar formulation of drug:dimyristoyl-phosphatidycholine:polysorbate 80 (1:20:3.3) exhibited the maximum dissolution (75.27%), while pure progesterone resulted in low dissolution. The above formulation showed a 4-fold increase in transport in Caco-2 cells and a 6-fold increase in transport across the everted rat intestinal sac experiments compared with control. Proliposomal formulations enhance the extent of dissolution and membrane transport of progesterone and serve as ideal carriers for oral delivery of drugs with low water solubility.     

Polycystic ovary syndrome: Understanding the role of the brain

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the leading cause of anovulatory infertility. Characterised by hyperandrogenism, menstrual dysfunction and polycystic ovaries, PCOS is a broad-spectrum disorder unlikely to stem from a single common origin. Although commonly considered an ovarian disease, the brain is now a prime suspect in both the ontogeny and pathology of PCOS. We discuss here the neuroendocrine impairments present in PCOS that implicate involvement of the brain and review evidence gained from pre-clinical models of the syndrome about the specific brain circuitry involved. In particular, we focus on the impact that developmental androgen excess and adult hyperandrogenemia have in programming and regulating brain circuits important in the central regulation of fertility. The studies discussed here provide compelling support for the importance of the brain in PCOS ontogeny and pathophysiology and highlight the need for a better understanding of the underlying mechanisms involved.     

Prognosis,stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour,prior endocrine treatment and radiotherapy

AimA contralateral breast cancer (CBC) is today treated as an independent primary tumour, although recent data suggest risk and prognosis of CBC to be influenced by characteristics of and treatment given for the first tumour (BC1). We hereby investigate phenotypical and prognostic features of the second tumour (BC2) in relation to prior endocrine treatment and radiotherapy.MethodsFrom a well-defined population-based cohort of CBC-patients, we have constructed a unique tissue-microarray including 600 pairs of primary tumours and CBCs. Breast cancer mortality was primary end-point for prognosis.ResultsBoth oestrogen receptor (ER) status and stage was strongly correlated between BC1 and BC2 within CBC-pairs. Although BC2 had the highest prognostic impact, BC1 continued to influence prognosis after diagnosis of CBC. Patients diagnosed with two high stage tumours within a short time-interval had a particularly bad prognosis. Prior endocrine therapy and radiotherapy both correlated to ER-negativity of BC2. An ER-negative BC2 was associated with an inferior prognosis compared to an ER-positive BC2 regardless of ER-status of BC1 or prior endocrine therapy.ConclusionsOur results suggest that both the residual prognostic impact of BC1, the possibility of contralateral metastasis, as well as prior treatment given, need to be considered when determining appropriate diagnostic work-up and treatment of CBC. In addition, radiation to the contralateral breast and risk of inducing CBC with an aggressive ER-negative phenotype should be considered when establishing new radiation treatment techniques. This study indicates loss of ER-expression as an important ‘endocrine treatment escape mechanism’, although further studies are warranted.     

Progesterone receptors A and B and estrogen receptor alpha expression in normal breast tissue and fibroadenomas

Fibroadenomas are the most common benign breast tumors, occurring mainly in young women. Their responses to the hormonal environment are similar to those of normal breast tissue, which suggests that steroid receptors may play a role in tumor development. We evaluated the gene and protein expression of progesterone receptors A and B (PRA and PRB) and the protein expression of estrogen receptor α (ER-α) in fibroadenoma samples, comparing with adjacent normal breast tissue, from 11 premenopausal women. Progesterone and estradiol levels were determined. No alterations in the PRs gene and protein expression and the ER-α protein expression were observed between the follicular and luteal phases, in normal breast versus fibroadenomas. Protein levels of PRA and PRB were higher in fibroadenomas compared to normal breast tissue (P = 0.038 and P = 0.031), while the PRs mRNA levels were similar in both tissues (P = 0.721 and P = 0.139). There were no differences in ER-α protein expression between normal breast tissue and fibroadenomas (P = 0.508). The PRA:PRB ratio was similar in the tissues, and also showed a strong correlation in both (r = 0.964, P = 0.0001). Our data suggest a role of PRs in the growth and development of fibroadenomas, although without alterations of the PRA:PRB ratio in these tumors. The absence of alterations in ER-α protein levels could be a characteristic behavior of fibroadenomas, unlike breast cancer.     

金属硫蛋白在子宫内膜癌中的表达及意义

目的:探讨金属硫蛋白(MT)在子宫内膜癌中的表达及与雌孕激素受体(ER、PR)表达的关系。方法:应用免疫组织化学方法检测45例子宫内膜癌中MT及ER、PR的表达。结果:在子宫内膜癌中,MT的表达与手术-病理分期和组织学分级密切相关(P<0·05),但与肌层浸润无明显关系。另外,MT的表达还与ER、PR的表达呈负相关(P<0·05)。结论:联合测定ER、PR和MT含量有助于子宫内膜癌的诊断、治疗及预测预后。