P-钙粘蛋白在人类不同乳腺病中的差异表达及在鉴别诊断中的意义

目的通过研究P-钙粘蛋白在乳腺癌及硬化性腺病中表达的不同、淋巴结转移与P-钙粘蛋白表达的关系,探讨P-钙粘蛋白在硬癌和硬化性腺病鉴别诊断中的意义.方法采用免疫组化染色,观察硬癌和硬化性腺病中P-钙粘蛋白表达、淋巴结转移与淋巴结未转移病例P-钙粘蛋白的表达,利用图像分析系统对乳腺癌,尤其是硬癌细胞中P-钙粘蛋白的表达强度、淋巴结转移与淋巴结非转移病例P-钙粘蛋白的表达强度进行分析.结果 P-钙粘蛋白的表达在硬癌和硬化性腺病、淋巴结转移与淋巴结非转移病例中有显著差异(P<0.05).结论 P-钙粘蛋白的表达可作为硬癌和硬化性腺病鉴别诊断的参考指标,并对估计是否出现淋巴结转移具有一定意义.     

Fine needle aspiration cytology of sclerosing adenosis of the breast

OBJECTIVE: To analyze the cytologic findings of sclerosing adenosis of the breast. STUDY DESIGN: We reviewed the fine needle aspiration (FNA) cytologic slides of 7 cases of sclerosing adenosis of the breast and compared the cytologic findings with those of 10 cases of fibroadenoma and 7 cases of fibrocystic change. RESULTS: The smears of sclerosing adenosis were moderately to markedly cellular, consisting of small to large groups of benign epithelial cells arranged with variable architecture. Acinar sheets, scattered individual epithelial cells and small, dense, hyalinized stroma were found in all cases of sclerosing adenosis. Epithelial cells in sclerosing adenosis appeared more frequently as acinar sheets and discohesive individual cells than did those of fibroadenoma (P < .05). However, the branching pattern of epithelial sheets, large sheets and bipolar, naked nuclei were commonly found in fibroadenoma (P < .05). Fibroadenoma had large, hypocellular, fibromyxoid stroma, whereas sclerosing adenosis had small, dense, hyalinized stroma occasionally attached to the epithelial sheets. As compared with fibrocystic change, sclerosing adenosis had similar findings but showed more abundant cellularity, acinar sheets and individual epithelial cells, and the presence of stroma (P < .05). CONCLUSION: Findings of frequent acinar sheets and small, dense, hyalinized stroma attached to epithelial sheets can aid the FNA cytologic diagnosis of sclerosing adenosis. Awareness of the presence of scattered individual epithelial cells in cytologic smears of sclerosing adenosis can help prevent a misdiagnosis of malignancy.     

UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker.

Mucin O-glycosylation is characterized in cancer by aberrant expression of immature carbohydrate structures (Tn, T, and sialyl-Tn antigens). The UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-T) family enzymes regulate the initial steps of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. Considering that we recently found the ppGalNAc-T6 mRNA expressed in breast carcinomas, we produced a highly specific monoclonal antibody (MAb T6.3) to assess the expression profile of ppGalNAc-T6 protein product in breast tissues. The expression of ppGalNAc-T6 by breast carcinoma cells was confirmed on MCF-7 and T47D cell lines. In formalin-fixed tissues, ppGalNAc-T6 expression was observed in 60/74 (81%) breast cancers, 21/23 (91.3%) adjacent ductal carcinoma in situ (DCIS), 4/20 benign breast lesions (2/2 sclerosing adenosis and 2/13 fibroadenoma), and in 0/5 normal breast samples. We observed a statistically significant association of ppGalNAc-T6 expression with T1 tumor stage. This fact, as well as the observation that ppGalNAc-T6 was strongly expressed in sclerosing adenosis and in most DCIS, suggests that ppGalNAc-T6 expression could be an early event during human breast carcinogenesis. Considering that an abnormal O-glycosylation greatly contributes to the phenotype and biology of breast cancer cells, ppGalNAc-T6 expression could provide new insights about breast cancer glycobiology.     

Intervention studies in breast diseases

Based on results of comprehensive examination of 20,000 females with different breast diseases in a specialized mammological room, the paper presents the most informative invasive techniques that combine diagnostic and therapeutical potentialities, such as ductography, cystography using various sclerosing solution, various types of needle biopsies under X-ray guidance, stereotactic computer devices, ultrasound study, and various labeling modes for nonpalpable formation before surgery. It shows in expedient to make a comprehensive examination under the conditions of a mammological room where the advantages of this or that invisable intervention, including those without a dosage load, are rationally, without duplicating, used depending on the diseases detected, which increases the significance of preoperative diagnosis up to 95-98%, including that of nonpalpable formations by substantially reducing the proportion of surgical interventions into the breast.     

Surgical Management for Early-Stage Bilateral Breast Cancer Patients in China

Background

The aim of this study was to investigate the current surgical management strategy for bilateral breast cancer (BBC) patients and to assess the changes in this strategy in China.

Methods

This is a retrospective review of all patients with early-stage BBC who underwent surgical treatment at the Fudan University Shanghai Cancer Center between June 2007 and June 2014.

Results

A total of 15,337 patients with primary breast cancer were identified. Of these patients, 218 (1.5%) suffered from synchronous bilateral breast cancer (sBBC), and 296 (2.0%) suffered from metachronous bilateral breast cancer (mBBC). Patients with a lobular carcinoma component, those with estrogen receptor-positive cancer, and those with an accompanying sclerosing adenosis in the affected breast tended to develop BBC. The rates of bilateral mastectomy, breast conserving therapy, reconstruction, and combined surgeries were 86.2%, 6.4%, 3.7%, and 3.7%, respectively, for patients with sBBC and 81.1%, 4.4%, 3.0%, and 11.5%, respectively, for patients with mBBC. The interval between bilateral cancers, age at first diagnosis of breast cancer, histopathological type, and stage have significant impacts on the choice of surgery for patients with BBC.

Conclusions

Bilateral mastectomy was the dominant surgical management for patients with BBC in China, despite the increased application of breast reconstruction surgery observed in recent years. Bilateral prosthetic breast reconstruction was the ideal choice for patients with sBBC. Chinese surgeons should take responsibility for patient education and inform their patients about their surgical options.     

乳腺内不可触及病灶的定位活检应用价值

目的:探讨乳腺内不可触及病灶(NPBL)的定位活检技术及其在乳腺癌早期诊断中的临床应用价值。方法:对彩超发现的4459个和钼靶发现的25个NPBL分别行麦默通旋切和钩丝定位活检,确定病灶的病理类型。结果:4459个NPBL中3196个病灶为乳腺腺病或伴纤维腺瘤样结节(71.7%),1198个为纤维腺瘤(26.9%),11个为分叶状肿瘤(0.2%),17个为导管内乳头状瘤(0.4%),9个为乳腺导管原位癌,5个为导管原位癌伴微浸润,23个为浸润性癌(恶性占0.8%)。25个钼靶发现的NPBL中乳腺腺病13例(52%),导管原位癌7例,导管原位癌伴微浸润2例,浸润性癌3例(恶性占48%)。结论:超声引导下麦默通和钼靶引导下钩丝定位切除可以对NPBL做出定性诊断,具备创伤小、手术时间短和定位精准等特点,对提高乳腺癌的早期诊断率、降低死亡率具有一定的临床应用价值。     

Outpatient screening and its place in better detection of breast tumors

The authors state their opinion on this problem by analyzing their 5-year use of their programme specially developed for detection of breast disease, mainly cancer, among females visiting specialized rooms of non-mammological profiles (gastroenterology, endocrinology, rheumatology, pulmonology, neurology, cardiology, hematology, nephrology, etc.) in the consulting polyclinics of regional (territorial) hospitals and large city hospital-polyclinic complexes. In this period, mammographic studies were made in 9169 women included into a breast cancer-risk group. Of them 1370 young female patients with well-developed glandular tissue that makes mammographic diagnosis of presumed masses difficult underwent breast ultrasonography. Abnormalities were found in 6092 (66.44%) patients. Breast cancer and nodal benign masses (including cysts and fibroadenomas) were detected in 278 (3.03%) and 669 (7.30%) women, respectively. The detection rates of unpalpable breast malignant and benign masses carcinomas were 0.4 and 3.03%, respectively. The findings allow the authors to recommend their proposed screening programme for wide use in large regional (territoreal), city, and town polyclinic complexes.     

The gray zone in breast fine needle aspiration cytology. How to report on it?

OBJECTIVE: To study the "gray zone" in breast fine needle aspiration cytology in which an unequivocal diagnosis cannot be reached with fine needle aspiration cytology findings. STUDY DESIGN: This study compared cytology and histopathology of 72 breast lesions in which an initial cytologic diagnosis of atypia was given. RESULTS: There were 36 benign (50%) and 36 malignant (50%) histologic biopsy cases in the cytologic atypia group. Anisonucleosis, chromatin and nuclear membrane irregularity, and presence of myoepithelial cells were significantly different in benign and malignant cases. CONCLUSION: The gray zone in breast fine needle aspiration cytology is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. Diagnosing gray zone pathology as atypical in fine needle aspiration cytology causes no delay in treatment as excisional biopsy is recommended for all equivocal cases.     

Fas 相关死亡结构域蛋白在乳腺癌中表达的临床病理研究

目的:探讨Fas相关死亡结构域蛋白(Fas-associated death domain protein,FADD)在乳腺癌中表达的临床病理学意义。方法:收集乳腺癌病例及相应的临床资料包括随访资料,应用免疫组织化学技术检测乳腺良性病变,有/无淋巴结转移的乳腺癌及配对淋巴结转移灶中FADD的表达,观察分析FADD表达与乳腺癌患者年龄、肿块大小、临床分期、组织学类型和分级、雌孕激素受体水平等临床病理指标间的关系。结果:免疫组化检测结果显示良性乳腺病变组中FADD的阳性表达率(85.1%,40/47)与无淋巴结转移的乳腺癌组(45.8%,38/83),伴有淋巴结转移的乳腺癌组(67.3%72/107)和淋巴结转移灶(45.8%,49/107)组织中FADD阳性表率均有显著性差异(P值分别0.001,=0.022和0.001);此外,伴有淋巴结转移的乳腺癌组中FADD阳性表达率也均与其它三组中FADD阳性表达率之间具有显著性差异(P值分别为0.003,0.001和0.022)。FADD与患者的确诊年龄(P=0.049)和淋巴结转移有显著性相关(P=0.003),与肿瘤大小、临床分期、组织学类型、组织学分级、雌孕激素受体及cerb B-2的表达情况和月经史无明显相关性(P0.05)。生存分析显示FADD阳性表达的患者较FADD阴性患者的生存期更短。结论:FADD与乳腺癌淋巴结转移和预后有关。     

A Clinicopathological Study of Early-Stage Synchronous Bilateral Breast Cancer: A Retrospective Evaluation and Prospective Validation of Potential Risk Factors

Background

The aim of the present study was to investigate potential risk factors for synchronous bilateral breast cancer sBBC).

Methods

A retrospective analysis was performed of patients diagnosed and treated with operable bilateral breast cancer (BBC) between June 2007 and December 2011. Risk factors for sBBC were evaluated in this cohort and further validated in a prospective observational validation analysis of patients between January 2012 and December 2012. Patients treated with operable unilateral breast cancer during the same period were used as a control group.

Results

A total of 11,247 patients with primary breast cancer underwent operations at the Fudan University Shanghai Cancer Center between June 2007 and December 2012. The incidence of sBBC was 1.6%. The age at diagnosis (HR = 2.4, 95% C.I.: 1.4–4.0, p = 0.001), presence of sclerosing adenosis (HR = 11.8, 95% C.I.: 5.3–26.3, p<0.001), lobular carcinoma component involvement (HR = 5.6, 95% C.I.: 2.6–12.1, p<0.001), and family history of first-degree relatives with breast cancer (HR = 2.0, 95% C.I.: 1.1–3.4, p<0.001) were independent risk factors for sBBC. A subsequent validation study failed to confirm the significance of family history. No significant difference on survival was found between patients with early-stage sBBC and control cases.

Conclusions

Patients with the presence of sclerosing in the affected breast, and lobular carcinoma component involvement may be at high risk for developing sBBC. This study supports the hypothesis that the host-carcinoma biological relationship, especially for the tumor microenvironment, played a critical role in the carcinogenesis of sBBC.     

Sentinel node biopsy in breast cancer using infrared laser system first experience with PDE camera

Background

Sentinel node biopsy (SNB) is a gold standard in staging of early breast cancer. Nowadays, routine mapping of lymphatic tract is based on two tracers: human albumin with radioactive technetium, with or without blue dye. Recent years have seen a search for new tracers to examine sentinel node as well as lymphatic network. One of them is indocyanine green (ICG) visible in infrared light.

Aim

The aim of this study is to evaluate clinical usage of ICG in comparison with standard tracer, i.e. nanocoll, in SNB of breast cancer patients.

Materials and methods

In the 1st Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznań, 13 female breast cancer patients have benn operated since September 2010. All these patients had sentinel node biopsy with nanocoll (human albumin with radioactive technetium), and with indocyanine green. The feasibility of this new method was assessed in comparison with the standard nanocoll.

Results

A lymphatic network between the place of injection of ICG and sentinel node was seen in infrared light. An area where a sentinel node was possibly located was confirmed by gamma probe. Sensitivity of this method was 100%.

Conclusion

SNB using ICG is a new, promising diagnostics technique. This procedure is not without drawbacks; nevertheless it opens new horizons in lymphatic network diagnostics.     

The impact of operative approach on outcome of surgery for gastro-oesophageal tumours

Background

Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens.

Methods

Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data.

Results

No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers.

Conclusion

In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.     

The p53 tumor suppressor gene

p53 was originally considered to be a nuclear oncogene, but several convergent lines of research have indicated that the wild-type gene functions as a tumor suppressor gene negatively regulating the cell cycle. Mutations in the p53 gene have been detected in many tumor types and seem to be the most common genetic alterations in human cancer. In this preliminary study, sera of 92 patients (pts) with breast disease were analyzed for the presence of the mutant p53 protein (mp53) with a selective immunoenzyme assay employing a monoclonal antibody (PAb 240) specific for the majority of mammalian m p53 but not for the wild-type protein. Of the 10 patients with benign breast disease, only two (20%) showed detectable m p53 levels in the serum. In the breast cancer group, sera from 7 of the 30 pts (23%) without lymph node involvement were positive for m p53, as were 7 out of the 45 pts (15%) with metastatic lymph nodes and 1 out of the 7 pts (14%) with disseminated disease. The specifity of m p53 assay evaluated in 20 healthy controls was 100%. These preliminary results showed that serum positivity for m p53 is not related to breast disease extension. Further studies to assess the utility of m p53 as a possible prognosis factor in breast cancer are currently in progress.     

The p53 tumor suppressor gene. A preliminary clinical study in breast cancer patients.

p53 was originally considered to be a nuclear oncogene, but several convergent lines of research have indicated that the wild-type gene functions as a tumor suppressor gene negatively regulating the cell cycle. Mutations in the p53 gene have been detected in many tumor types and seem to be the most common genetic alterations in human cancer. In this preliminary study, sera of 92 patients (pts) with breast disease were analyzed for the presence of the mutant p53 protein (mp53) with a selective immunoenzyme assay employing a monoclonal antibody (PAb 240) specific for the majority of mammalian m p53 but not for the wild-type protein. Of the 10 patients with benign breast disease, only two (20%) showed detectable m p53 levels in the serum. In the breast cancer group, sera from 7 of the 30 pts (23%) without lymph node involvement were positive for m p53, as were 7 out of the 45 pts (15%) with metastatic lymph nodes and 1 out of the 7 pts (14%) with disseminated disease. The specificity of m p53 assay evaluated in 20 healthy controls was 100%. These preliminary results showed that serum positivity for m p53 is not related to breast disease extension. Further studies to assess the utility of m p53 as a possible prognosis factor in breast cancer are currently in progress.     

HVEM Gene Polymorphisms Are Associated with Sporadic Breast Cancer in Chinese Women

As a costimulatory molecule, Herpesvirus entry mediator (HVEM) can bind with several costimulatory members, thus HVEM plays different roles in T cell immunity. HVEM and its ligands have been involved in the pathogenesis of various autoimmune, inflammatory diseases and tumors. In the current study, we conducted a case-control study comparing polymorphisms of HVEM and breast cancer. Subjects included 575 females with breast cancer and 604 age-matched healthy controls. Six HVEM SNPs (rs2281852, rs1886730, rs2234163, rs11573979, rs2234165, and rs2234167) were genotyped by PCR-RFLP. The results showed significant differences in genotypes and alleles between rs1886730 and rs2234167 (P<0.05). One haplotype (CTGCGG) that was associated with breast cancer was found via haplotype analysis. Our research also indicated an association between polymorphisms of HVEM and clinicopathologic features, including lymph node metastasis, estrogen receptor, progesterone receptor and P53. Our results primarily indicate that polymorphisms of the HVEM gene were associated with the risk of sporadic breast cancer in northeast Chinese females.     

乳腺肿块X线检查常见漏、误诊原因的病例分析

目的:分析乳腺X线检查的误漏诊原因,提高诊断准确性。方法:选择2011年3月至2013年12月来我院就诊的135例经乳腺X线摄影和病理检查证实的乳腺肿瘤患者为研究对象,将X线摄影结果与病理检查结果对比,进行回顾性的分析。结果:病理诊断72例良性肿瘤而X线误诊为恶性7例(误诊率9.72%);63例恶性肿瘤而X线误诊为良性5例(漏诊率7.93%)。结论:乳腺X线误诊与乳腺致密程度、患者年龄以及肿瘤形态相关。掌握拍片技术减少技术性误差,提高影像质量,诊断时仔细阅片并熟知各类型乳腺疾病的特征性X影像表象,并与临床相结合,增强责任心,可减少乳腺X线检查的误漏诊。     

Clinical and pathological characteristics of occult breast cancer and review of the literature

Purpose: Occult breast cancer is defined as axillary metastasis without clinically and/or radiologically evident primary tumor. In female patients presenting with isolated axillary nodes with adenocarcinoma, the most likely primary cancer is an invasive breast carcinoma. Herein we present our experience over this issue, together with a brief review of the literature about this clinically challenging condition. Methods: We retrospectively analyzed 1215 consecutive breast cancer patients treated at our clinic between 2004- 2010. Four of these patients presented with axillary nodal metastasis without clinical and radiological evidence of a primary breast tumor. Results: The incidence of occult breast cancer in our clinic was 0.32%. Median follow-up was 8 months. All patients were alive and remained free of disease at the end of the follow-up period. Conclusion: The prognostic factors for occult breast carcinoma are similar to that of its overt counterpart. The number of axillary lymph node involved and the hormone receptor status are considered significant prognostic predictors. Further studies with randomization and longer followup are needed for the establishment of a safe management plan.     

MCA in patients with breast cancer: correlation with CEA and CA15-3

MCA serum levels were determined in 27 healthy subjects, 136 with benign pathology (42 breast) and in 289 patients with cancer (247 active). The last group includes 223 patients with breast cancer (96 without metastases, 89 with metastases and 38 no-evidence of disease). CEA and CA15-3 serum levels were determined in all the patients with breast diseases. The mean levels of MCA were 4.7 + 2.4 U/ml in the control group, considering less than 11 U/ml as normal. MCA values were abnormal in 15.4% of patients with benign pathology, mainly in those with liver cirrhosis (8/20) and lung diseases (4/20). In the majority of these cases, the rise was only moderate, lower than 15 U/ml in 97.5% of patients. In malignant diseases, important increments were found in breast cancer (19.8% Mo, 77.5% M1) and ovarian cancer stages III-IV (44.4%). When we compared MCA serum levels with CA15-3 and CEA in breast pathology, a similar specificity was observed: 92.3%, 92.3% and 100% in cases with benign pathology and 92.1%, 94.7%, and 97.4% in NED patients, respectively. MCA and CA15-3 sensitivity was similar in breast cancer without metastases (19.8%) and lower for CEA (16.7%). In patients with breast cancer without metastases, we found a relation between positivity of these tumor markers and prognostic factors (tumor size, nodal involvement). The disease free interval in patients with locoregional breast cancer was shorter in cases with abnormal presurgical levels of some of the tumor markers, but only the difference from MCA was significant (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)