Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

The recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in gene-expression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.     

采用表面增强激光解吸离子化飞行时间质谱技术筛选乳腺癌新辅助化疗敏感蛋白谱

目的应用表面增强激光解吸离子化飞行时间质谱（SELDI-TOF MS）技术检测乳腺癌新辅助化疗前后癌组织内蛋白质谱的变化,筛选乳腺癌新辅助化疗敏感性相关蛋白质。方法 60份样本来自2009年3月至2010年8月山东省千佛山医院乳腺外科收治的30例乳腺癌患者CEF新辅助化疗前后的乳腺癌组织。化疗前,行粗针穿刺获得乳腺癌组织;化疗后,在乳腺癌根治术中取样。应用SELDI-TOF MS技术检测乳腺癌组织的蛋白质谱,所得数据采用Biomarker wizard 3.0.2软件分析,得到差异蛋白谱,再采用SPSS17.0软件对数据进行Shapiro-Wilk正态性检验和配对设计t检验。根据差异蛋白质的质荷比,在SWISS-PROT数据库中检索与差异蛋白质相匹配的存在于乳腺组织或乳腺癌组织中的蛋白质。结果通过比较患者新辅助化疗前后的蛋白峰值,筛选出8个蛋白峰有差异的蛋白质,其质荷比（m/z）分别为5825.9、8949.5、11053.5、11652.0、17898.9、22250.6、26055.5、38546.6,化疗后这8个蛋白峰均高于化疗前（11.0±5.0比8.2±4.9、10.7±4.5比6.3±3.4、22.3±9.9比15.3±9.9、28.0±10.2比21.4±9.3、9.5±4.6比5.4±3.4、1.1±1.0比0.6±0.5、2.0±0.7比1.5±0.7及2.7±2.2比1.5±1.2,P值均〈0.05）。结论应用SELDI-TOF MS技术可以筛选出与乳腺癌新辅助化疗敏感性相关的蛋白质谱。     

Presurgical determination of estrogen receptor status using immunocytochemically stained fine needle aspirate smears in patients with breast cancer

We have developed an immunocytochemical staining procedure (ERICA) using a monoclonal antibody to the estrogen receptor (ER) to determine ER status from samples obtained by fine needle aspiration of primary and recurrent breast cancer tissue (cyto-ERICA). ER status was assessable on 214 of 246 smeared aspirates from breast cancer patients. In 143 (66.8%) assessable smears positive nuclear staining was observed but was completely absent in 71 (33.2%) cases. In 107 cases we were able to compare results with those obtained with the quantifiable dextrancoated charcoal (DCC) radioligand binding technique using surgically excised material. We observed qualitative agreement in 53 of 62 (85.5%) of primary specimens and 16 of 16 (100%) recurrent samples compared to the subsequent DCC result on the same sample. Aspirates obtained from new secondary deposits were also assessed and in 16 of 19 (84.2%) cases results agreed with that established previously by DCC on the primary breast tumor. In a further 6 of 10 (60%) cases the cyto-ERICA result obtained from recurrent samples qualitatively agreed with that determined by DCC on a previous recurrent lesion. A comparison of staining of aspirates was also made against frozen tissue sections stained with the monoclonal antibody (tissue-ERICA). Where comparison was made of primary tumor specimens agreement was observed in 40 of 45 (88.9%) of cases while specimens from secondary lesions agreed qualitatively in 14 of 17 (82.3%) of cases. In a small number of samples where tissue-ERICA was performed on an earlier lesion to that aspirated for cyto-ERICA an agreement of 4 of 5 (80%) was observed. This technique shows good sensitivity in demonstrating ER in aspirate specimens, should therefore permit us to determine ER status before surgery for primary breast cancer, and may also mean that surgery for recurrent disease to determine receptor status is no longer necessary.     

Management and prevention of complications of subcutaneous intravenous infusion port

Subcutaneous intravenous infusion port (SIIP) has become an increasingly and widely adopted technique in the management of oncology patients. This route has been used not only for chemotherapy but also for parenteral nutrition provision, blood transfusion, medication administration, blood sample collection, hemodialysis, and so on. This system provides a safe vascular access with low complication rate which helps preventing patients from vascular infection and catheter associated thrombosis. In this study, we reviewed 1247 cases of breast cancer patients that had subcutaneous intravenous infusion port implanted for chemotherapy in our general surgery department from 1990 to 2008. The result indicates that complication decreases as our technique and experience mature. We hereby share our accrued experience and improved technique, hoping to be of help to young surgeons.     

乳腺癌保留乳头乳晕成型术的临床病理研究

目的 :为保留乳头乳晕的乳腺癌成型术提供临床病理基础。方法 :采用临床资料的分析与病理相结合的方法、将乳腺癌患者的乳头和乳晕整体标本连续切片病理检查。用流式细胞技术进行癌组织DNA倍体分析、免疫组化法增殖细胞核抗原 (PCNA)含量测定。进一步分析乳腺癌患者保留乳头和乳晕的安全性和可能性。为乳腺成型提供实践依据。结果 :检测肿瘤至乳晕的平均距离为 1 9.6毫米 ,侵犯乳头乳晕共 5例 ,其中Ⅲb 3例、Ⅳ期 2例。这 5例DNA倍体均为异倍体。PCNA阳性 50 %～ 75 %及 >75 %占Ⅲ、Ⅳ期乳腺癌的 77.78%。结论 :乳晕旁1 .96厘米以外的乳房肿瘤有保留乳房的适应证 ,肿瘤位于乳晕下方、临床分期Ⅲ期及Ⅳ期无保留乳房的适应证。严格掌握保留乳头乳晕的适应证条件 ,乳腺癌保留乳房成型术才能更加安全     

Breast cancer in older patients

Breast cancer is a common problem and a major health concern in our growing geriatric population. Older breast cancer patients are at risk for less than standard management, the appropriateness of which is difficult to discern. Breast tumors tend to have less aggressive characteristics. In addition, planning therapy is not always straightforward because older patients may present with comorbid illnesses and frailty that limit therapeutic choices. Standard management approaches should always be considered first. Here, we outline some data supporting standard treatment for breast cancer in older women. We also describe other options that can be considered in circumstances when the standard treatment is not possible. For instance, primary treatment with tamoxifen or an aromatase inhibitor is justifiable in a patient who is unfit for surgery and axillary dissection may be unnecessary in a patient who is obviously unfit for adjuvant chemotherapy. Adjuvant therapies should be considered, weighing risks and benefits for each patient, though the threshold for using chemotherapy may be higher. The goals in treating metastatic breast cancer in an older patient are not different than for younger patients.     

Methylated NEUROD1 promoter is a marker for chemosensitivity in breast cancer.

PURPOSE: Chemotherapy can be an integral component of the adjuvant management strategy for women with early stage breast cancer. To date, no tool is available to predict or monitor the efficacy of these therapies. The aim of this proof-of-principle study was to assess whether NEUROD1 DNA methylation is able to predict the response to neoadjuvant and adjuvant chemotherapy. EXPERIMENTAL DESIGN: Recently, we showed that NEUROD1 DNA is differentially methylated in neoplastic versus nonneoplastic breast tissue samples. In this study, we used MethyLight and analyzed NEUROD1 methylation in (a) 74 breast cancer tissue samples, (b) two independent sets of pretreatment core biopsies of 23 (training set) and 21 (test set) neoadjuvantly treated breast cancer patients, and (c) pretherapeutic and posttherapeutic serum samples from 107 breast cancer patients treated with adjuvant chemotherapy. RESULTS: High-grade tumors showed higher NEUROD1 methylation levels. Estrogen receptor-negative breast cancers with high NEUROD1 methylation were 10.8-fold more likely to respond with a complete pathologic response following neoadjuvant chemotherapy. Patients with positive serum pretreatment NEUROD1 methylation, which persisted after chemotherapy, indicated poor relapse-free and overall survival in univariate and multivariate analyses (relative risk for relapse, 6.2; 95% confidence interval, 1.6-24; P = 0.008, and relative risk for death, 14; 95% confidence interval, 1.6-120; P = 0.02). CONCLUSIONS: These data support the view that NEUROD1 methylation is a chemosensitivity marker in estrogen receptor-negative breast cancer.     

晚期乳腺癌的综合治疗

晚期乳腺癌在临床工作中并不少见，由于乳腺癌对化疗及放射治疗均比较敏感。只要进行积极的综合治疗，效果尚比较满意。治疗过程中，应根据病人的机体情况、肿瘤的病理类型、不同的转移部位，合理的有计划的综合应用现有的治疗手段，组成以化疗为主的综合治疗方案，以期较大限度的提高病人的缓解率，改善病人的生活质量，延长病人生存时间。本组治疗晚期乳腺癌病人９３例，中位生存期为２１个月、１年生存６８．８％、３年生存２５．８％、５年生存１０．７％。以肺及骨的治疗效果较好，而肝及脑转移的病人效果较差。化疗方案使用ＣＭＦ、ＣＡＦ、ＣＭＶＰ进行三级治疗，效果较满意。     

Immunohistochemical localization of the plasminogen activator inhibitor-1 in breast cancer

We used an immunohistochemical assay with an antigen-retrieval technique to study plasminogen activator inhibitor type-1 (PAI-I) expression in paraffin-embedded breast tissue samples at different stages of malignant transformation. We detected PAI-I in 15/20 invasive tumors. In several cases staining was localized to the stromal component. PAI-I-positive fibroblasts could be seen surrounding tumor nodules or at tumor margins. In addition, tumor-infiltrating macrophages (13 cases) and endothelial cells (5 cases) were positive. In 11 specimens PAI-I-positive cancer cells were also detected. In 2 strongly positive cases secreted PAI-I was visible in the extracellular matrix surrounding the cells. Six of 9 samples of carcinoma in situ (DCIS) were weakly positive. No staining of endothelial cells was visible in DCIS. Only a few positive adenomatous epithelial cells could be seen in 3 of 7 papillomas. All biopsies of normal breast tissue were negative, with the exception of one sample, obtained from a patient with a previous segmental mastectomy for DCIS. PAI-I production by invasive breast cancers could reflect a general upregulation of the plasminogen activation system in proliferating cancer cells, as suggested by the finding that normal mammary epithelium cultures expressed PAI-I in all cases examined. In addition, production of PAI-1 by the tumor stroma could protect the tumor itself from excessive proteolysis.     

Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers

PURPOSE: Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Noninvasive imaging that can monitor angiogenesis may be invaluable initially for diagnosis and then for assessing tumor response to treatment. By combining ultrasound (US) and near-infrared (NIR) optical imaging, a reliable new technique has emerged for localizing and characterizing tumor angiogenesis within the breast. METHODS: This new technique employs a commercial US transducer coupled with an array of NIR optical fibers mounted on a hand-held probe. The US image is used for lesion localization and for guiding optical imaging reconstruction. Optical sensors are used for imaging tumor total hemoglobin distribution, which is directly related to tumor angiogenesis. RESULTS: Six large breast carcinomas were studied and microvessel density count was then performed on tissue samples obtained from these cancers. Two patients had locally advanced breast cancers and received neoadjuvant chemotherapy for 3 months. In one patient, before chemotherapy, the total hemoglobin distribution showed a high concentration at the cancer periphery; the distribution was later confined to the core area after 3 months of treatment. In another patient, as treatment progressed, the maximum hemoglobin concentration decreased from 255.3, to 147.5, to 76.9 micromol/l with an associated reduction in spatial extension. The other four patients had cancers of 2.0 to 3.0 cm in size and were imaged either at the time of core biopsy or definitive surgery. The histologic microvessel density counts from these tumor samples correlate to hemoglobin distributions with a correlation coefficient of 0.64 (P < .05). CONCLUSION: These initial results suggest that this new imaging technique may have great potential in imaging the heterogeneous vascular distribution of larger breast cancers in vivo and in monitoring treatment-related changes in angiogenesis during chemotherapy.     

Extending the duration of first-line chemotherapy in metastatic breast cancer: a perspective review

The treatment of metastatic breast cancer is mainly palliative, but optimal management might result in survival improvement as well. For this reason, many trials have attempted to optimize the therapeutic approach in this disease setting. Among the possible options, chemotherapy represents the backbone of the treatment and survival improvements that have been shown by the use of modern chemotherapeutic agents. Whereas the type of chemotherapy is generally dictated by patient characteristics and those of their disease, substantial controversy still remains on how long chemotherapy should be administered after disease control is achieved. In this review, we have analysed all available evidence on the duration of first-line chemotherapy in advanced breast cancer.     

新辅助化疗对进展期乳腺癌患者 CD46表达影响及临床预后预测意义的研究

目的：探讨CD46在进展期浸润性乳腺癌及正常乳腺组织中的表达水平,并分析其与乳腺癌患者新辅助化疗疗效的关系,探讨其在乳腺癌新辅助化疗预后评估方面的预测价值。方法采用免疫组化的方法检测60例浸润性乳腺癌组织及30例正常乳腺组织标本CD46的表达,并分析该表达与新辅助化疗疗效的关系,采用生存分析预测CD46表达对患者预后的意义。结果乳腺癌组织CD46阳性率明显高于正常乳腺组织（81．67％vs．46．67％,P＜0．05）;新辅助化疗后,CD46表达阳性率明显下降（P＜0．05）,CD46表达阳性率与患者化疗疗效呈负相关关系（P＜0．05）;CD46阳性表达提示患者的生存预后较差,浸润程度、有无淋巴结转移、CD46表达是乳腺癌新辅助化疗技术有效与否的独立影响因素（ P＜0．05）。结论乳腺癌患者的CD46表达高于健康者,与新辅助化疗技术的临床疗效呈负相关,CD46阳性表达率升高对患者较差的预后具有一定的预测价值。     

Use of a physician-directed questionnaire to define a consensus about management of breast cancer: implications for assessing costs and benefits of treatment.

The present study was designed to assess the preferred methods of treatment of early breast cancer by United States oncologists, to define the impact of published clinical trials on their practice, and to define questions related to clinical decision making that should be subjected to further research. A questionnaire was mailed to 405 oncologists of all three disciplines (medical, radiation, and surgical oncology) and to 60 oncology nurses who practice in the United States. The questionnaire included clinical scenarios of: (a) a patient with primary breast cancer; (b) a premenopausal woman with node-negative breast cancer; and (c) a postmenopausal woman with estrogen receptor (ER)-negative, node-positive breast cancer. Respondents were asked to describe their preferred management for each scenario. Our study demonstrates a consensus that modified radical mastectomy, or partial mastectomy plus radiation therapy, should be offered as equal options to selected patients with primary breast cancer; this consensus is supported by results of clinical trials. We also found agreement that adjuvant chemotherapy should be offered to premenopausal women with node-negative, ER-negative breast cancer. There was a similar consensus in favor of adjuvant chemotherapy for postmenopausal patients with ER-negative, node-positive breast cancer, despite the absence of improvement in overall survival in large, mature, controlled randomized trials (and in a meta-analysis). We suggest that further research be undertaken into factors that influence decision making by oncologists when they consider the administration of adjuvant chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Duodenal metastasis from recurrent invasive lobular carcinoma of breast: a case report and literature review

We present a rare case of duodenal metastasis from invasive breast lobular carcinoma, which first presented clinically as elevated serum tumor marker levels, followed by jaundice but with no other clinical evidence of recurrence and metastasis. A 53-year-old woman underwent modified radical mastectomy of the left breast (pT2 N3 M0 stage III c) followed by postoperative chemo-radiotherapy and hormonal therapy. After about 3 years, the patient presented with elevated serum tumor marker levels and mild jaundice. She was subsequently admitted to the hospital for nausea and severe vomiting. A duodenoscopy revealed the thickening of duodenal papilla on the lateral wall and stenosis. A duodenal tissue biopsy revealed poorly differentiated adenocarcinoma, and immunohistochemical staining suggested that the carcinoma was of breast origin. The patient received further radiation and chemotherapy. Although duodenal metastases of breast cancer are rare, physicans should be alert and vigilant when a patient with a history of breast cancer presents with new gastrointestinal symptoms.     

乳腺癌组织BRCA1、BRCA2基因区域杂合性缺失的研究

目的　研究乳腺癌组织BRCA1、BRCA2基因区域的杂合性缺失 (LOH)情况。方法　采用聚合酶链式反应(PCR)和聚丙烯酰胺凝胶电泳 ,对 30例散发性乳腺癌和 2例姐妹乳腺癌进行LOH的检测 ,同时还采用G显带法对姐妹乳腺癌患者的外周血淋巴细胞染色体畸变情况进行分析。结果　在散发性乳腺癌中 ,BRCA1、BRCA2基因区域的杂合性缺失率分别为 6 12 %和 5 77% ;姐妹二人乳腺癌组织在BRCA2基因区域的D13S173位点处存在LOH ,且她们的外周血淋巴细胞发生了大量的稳定性和非稳定性畸变 ,畸变率远远高于自发畸变率。结论　乳腺癌易感机理在东西方种族有可能存在差异 ,应深入进行研究     

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

Aims: Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumorprogression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breastcancer. Methods: Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels inserum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined andassessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishingbetween the four sample types, we created receiver operating characteristic (ROC) curves. Results: The mtDNAlevels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue,reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROCcurve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue sampleswith good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue werepositively associated with cancer TMN stage. Conclusions: The mtDNA levels in blood samples may representa promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies arerequired to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.     

Mastopathy of the accessory breast in the bilateral axillary regions occurring concurrently with advanced breast cancer

Summary We herein report a 41-year-old Japanese woman who demonstrated advanced cancer in the left breast occurring concurrently with mastopathy of the accessory breast tissue in the bilateral axillary regions, which appeared to be metastatic lymphadenopathy. A preoperative examination, including a mammogram, US, and CT, did not provide us with a definite diagnosis of the axillary masses: it was essential to diagnose the masses preoperatively since a bilateral mastectomy with nodal dissection is called for if the right axillary masses are metastatic from a cancer in the right breast. An intraoperative cytological examination from the bilateral axillary masses revealed adenosis with fibrocystic changes in the accessory breast tissue. We therefore performed a modified radical mastectomy only on the left side. The patient was thus saved from an unnecessary mastectomy of the right breast.Based on our experience, we wish to emphasize that the accessory breast tissue should be considered for a differential diagnosis when evaluating the axillary masses in order to avoid over-surgery, especially when a patient has been diagnosed to have massive breast cancer. An intraoperative cytological examination is strongly recommended to reach a final diagnosis in such confusing cases.     

Breast cancer in men

Most men with breast cancer present with a mass in the breast, the evaluation of which should include a tissue diagnosis. If the presence of invasive cancer is established, adequate local therapy includes total removal of the breast. Most tumors are hormone-receptor positive. In high-risk patients, the use of endocrine adjuvant therapy and/or combined endocrine and chemotherapy should be considered. Patients with estrogen-receptor (ER)-negative disease should be offered chemotherapy. In patients with metastatic disease and ER-positive tumors, initial treatment should be endocrine therapy; systemic chemotherapy should be used in patients who are either hormone-receptor negative or resistant to available endocrine therapies.     

An efficient method for culturing human breast epithelium: analysis of results.

We have examined the possibility of obtaining primary cultures from breast tissue utilizing a method especially developed for breast epithelium. The number of specimens able to grow in culture was very high: 82.8%, 64.3%, 75.0% and 77.8%, respectively, for primary breast cancer, skin recurrences, inflammatory breast cancer and normal breast tissue. In our experience, growth was not related to menopausal status or histopathologic type, whereas for skin recurrences, a prior pharmacologic treatment (chemotherapy) of the patient enhanced the growth capacity of the tissue. This culture method could help to study the basic biology of breast epithelia and to improve the chemotherapy approach of breast cancer patients.