Fibroadenoma of the breast with florid epithelial cells hyperplasia: a case report

Fibroadenoma is a benign biphasic tumor of the breast, composed of an epithelial and a stroma component. Fibroadenoma with epithelial cells hyperplasia may contribute to the higher risk of breast cancer, especially for florid and atypical hyperplasia. The distinction between fibroadenoma with florid epithelial cells hyperplasia, in-situ carcinoma and invasive duct carcinoma of the breast ban be difficult morphologically. To solve the problem, immunohistochemical staining with specific andibodies will be helpfull in distinguishing usual duct hyperplasia from ductal carcinoma in situ. A case of fibroadenoma with florid epithelial cells hyperplasia has been reported. Morphologically, this tumor is difficult to be differentiated from ductal carcinoma. Immunohistochemical staining with High molecular weight cytokeratins 34BE12, Smooth Muscle Actin (SMA),E-cadherin could be used to determine the diagnosis of this tumor

Immunohistochemical categorisation of ductal carcinoma in situ of the breast

The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma. Immunohistochemistry of pure DCIS cases constructed in tissue arrays was performed with 16 markers (oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Bcl-2, p53, Her2, insulin-like growth factor receptor, E-cadherin, epithelial membrane antigen (EMA), CA125, keratins 5/6, 14, 19, epidermal growth factor receptor, S100, and CD31). Results in 163 cases were analysed by unsupervised hierarchical clustering. Histological classification was performed by review of whole tissue sections and identified 36 well-, 55 intermediately, and 72 poorly differentiated DCISs. Unsupervised hierarchical cluster analysis categorised DCIS into two major groups that could be further subdivided into subgroups based on the expression of six markers (ER, PR, AR, Bcl-2, p53, and Her2). In the major predominantly ER/Bcl-2-positive (luminal) group, three subgroups (AR-positive (n=33), AR-negative (n=40), and mixed (n=34)) could be identified and included 34 well-differentiated DCISs. Within the major predominantly ER/Bcl-2-negative (nonluminal) group, a Her2-positive subgroup (n=34) was characterised by 31 poorly differentiated lesions. Eight triple-negative lesions, including one positive for keratin 5/6 and two positive for p53, were encountered. Intermediately differentiated DCIS shared a comparable IHC staining pattern with well-differentiated DCIS that was distinct from poorly differentiated DCIS (P<0.001). Ductal carcinoma in situ could be categorised by IHC into two major groups and five subgroups using six markers. Morphologically, intermediately differentiated DCIS seems to have more biological similarities with well-differentiated lesions as compared to poorly differentiated lesions

Hormone replacement therapy, mammography screening and changing age-specific incidence rates of breast cancer: an ecological study comparing two European populations

Background: In 2003, for the first time, US breast cancer incidence rates have fallen. Experts argue whether this is due to the reduced uptake of screening mammography or to lower use of Hormone Replacement Therapy (HRT). This study aims to disentangle the respective impact of screening and HRT on age-incidence rates and histology of breast cancer, by comparing two populations with comparably high levels of screening mammography, but with different prevalence of HRT. Methods: We included all invasive breast cancers recorded at the Geneva cancer registry (n=4,909) and the Netherlands Cancer Registry (n=152,428) between 1989-2003. We compared age-specific incidence rates and trends in histological subtyping between the two populations. Results: Between 1989-1991, incidence rates increased with age in both populations. In 2001-2003, women aged 60-64years showed highest incidence rates in Geneva, while in the Netherlands incidence rates continued to increase with age. The annual increase in ductal cancer incidence was similar in the Netherlands (2.3%) and Geneva (2.5%), but the annual increase in lobular cancer was sharper in Geneva (10%) than in the Netherlands (5%). Conclusion: The sharp differences in age distribution and histological subtyping of breast cancer between two European populations are not attributable to screening, since both populations have a high uptake of mammography screening. Since the prevalence of HRT use is very high in Geneva and rather low in the Netherlands, HRT may explain these discrepancies. However, other etiological factors and differences in histological assessment may also have played a rol

Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies.

Five patients with a pleural malignancy (four malignant mesotheliomas and one localized low grade carcinoid) were treated with maximal surgical resection of the tumour followed by intraoperative adjuvant photodynamic therapy (PDT). The additional photodynamic treatment was performed with light of 652 nm from a high power diode laser, and meta-tetrahydroxy phenylchlorin as the photosensitizer. The light delivery to the thoracic cavity was monitored by in situ isotropic light detectors. The position of the light delivery fibre was adjusted to achieve optimal light distribution, taking account of reflected and scattered light in this hollow cavity. There was no 30-day post-operative mortality and only one patient suffered from a major complication (diaphragmatic rupture and haematopericardium). The operation time was increased by a maximum of 1 h to illuminate the total hemithoracic surface with 10 J cm(-2) (incident and scattered light). The effect of the adjuvant PDT was monitored by examination of biopsies taken 24 h after surgery under thoracoscopic guidance. Significant damage, including necrosis, was observed in the marker lesions with remaining malignancy compared with normal tissue samples, which showed only an infiltration with PMN cells and oedema of the striated muscles cells. Of the five patients treated, four are alive with no signs of recurrent tumour with a follow-up of 9-11 months. One patient was diagnosed as having a tumour dissemination in the skin around the thoracoscopy scar and died of abdominal tumour spread. Light delivery to large surfaces for adjuvant PDT is feasible in a relatively short period of time (< 1 h). In situ dosimetry ensures optimal light distribution and allows total doses (incident plus scattered light) to be monitored at different positions within the cavity. This combination of light delivery and dosimetry is well suited for adjuvant treatment with PDT in malignant pleural tumours

Histological type and marker expression of the primary tumour compared with its local recurrence after breast-conserving therapy for ductal carcinoma in situ

We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed for 71 cases. Comparing the primary DCIS and the invasive or non-invasive recurrence, concordant histology was found in 62%, and identical marker expression in 63%. Although 11% of the recurrences developed at a distance from the primary DCIS, nearly all these showed the same histological and immunohistochemical profile. 5 patients developed well-differentiated DCIS or grade I invasive carcinoma after poorly differentiated DCIS. Although these recurrences occurred in the same quadrant as the primary DCIS, they may be considered as second primary tumours. Only 4 patients developed poorly differentiated DCIS or grade III invasive carcinoma after well differentiated DCIS. We conclude that in most cases the primary DCIS and its local recurrence are related histologically or by marker expression, suggesting that local recurrence usually reflects outgrowth of residual DCIS; progression of well differentiated DCIS towards poorly differentiated DCIS or grade III invasive carcinoma is a non-frequent event. © 2001 Cancer Research Campaign http://www.bjcancer.co

Solid-phase synthesis of macrocyclic peptides via side-chain anchoring of the ornithine delta-amine

Cyclic peptides represent a popular class of macrocyclic drug candidates and therefore their solid phase synthesis has attracted much attention. In this contribution we present an efficient method of side-chain anchoring for ornithine and lysine residues to be used in the standard Fmoc-based synthesis of cyclic peptides via on-resin cyclization. We demonstrate that the side chain of ornithine and lysine protected with N-Bocgroup can efficiently be converted to the isocyanate which is then immobilized on Wang-type resin in almost quantitative yield. We further show the synthesis of four biologically active cyclic peptides employing the side chain ornithine anchoring. Our method is at least on a par with the previously reported methodologies in terms of yield and the purity of the final products and is arguably operationally more straightforward.NWOGravitation program 2013Bio-organic Synthesi