A Case Report of Post-Radiotherapy c-MYC-Positive Angiosarcoma of the Breast.

Angiosarcoma of the breast is an unusual malignancy and carries a poor prognosis, with a 5-year overall survival rate ranging from 27 to 48%. Radiotherapy-induced angiosarcoma (RIAS) of the breast is very uncommon, with an estimated incidence of 1 in 1,000 cases of breasts treated with radiotherapy for breast cancer. The increase in radiotherapy usage may lead to an increased incidence of RIAS. A case presentation of a 67-year-old patient with tubular adenocarcinoma of the left breast who developed c-MYC-positive RIAS of the breast is presented. The patient was successfully treated with surgery. We presented a classic case of c-MYC RIAS. c-MYC was reported to be positive in RIAS and other types of angiosarcomas. Clinical examination and early detection of RIAS breast angiosarcoma is vital to improving outcomes in these patients.

Clinical evaluation and budget impact analysis of cervical cancer screening using cobas 4800 HPV screening technology in the public sector of South Africa.

Cytology remains the mainstay of cervical cancer screening in South Africa (SA), however false negative rates are 25-50%. In contrast, human papillomavirus (HPV) screening techniques have higher sensitivity for cervical cancer precursors. The cobas® 4800 HPV test detects pooled high-risk HPV types and individual genotypes HPV 16 and 18. Using a mathematical budget impact model, the study objective was to evaluate the clinical and budget impact of replacing primary liquid-based cytology (LBC) with primary HPV-based screening strategies. In SA, current LBC screening practice recommends one test every ten years, followed by large loop excision of the transformation zone (LLETZ) if indicated. HPV testing can be performed from an LBC sample, where no additional consultations nor samples are required. In the budget impact model, LBC screening for 2 cycles (one test every ten years) was compared to cobas® 4800 HPV test for 2 cycles (one test every 5 years). The model inputs were gathered from literature and primary data sources. Indicative prices for LBC and cobas® 4800 HPV test were R189 and R457, respectively. Model results indicate that best outcomes for detection of disease were seen using cobas® 4800 HPV test. Forty-eight percent of cervical cancer cases were detected compared to 28% using LBC, and 50% of cervical intraepithelial neoplasia (CIN) 2 and CIN3 cases, compared to 25% with LBC. The budget impact analysis predicted that the cost per detected case of CIN2 or higher would be R 56,835 and R46,980 for the cobas® 4800 HPV and LBC scenarios, respectively. This equates to an incremental cost per detected case of CIN2 or higher of R9 855. From this model we conclude that a primary HPV screening strategy will have a significant clinical impact on disease burden in South Africa.

p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma.

PURPOSE: To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. RESULTS: The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of >70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. CONCLUSION: No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC.

Prevalence of myocarditis and cardiotropic virus infection in Africans with HIV-associated cardiomyopathy, idiopathic dilated cardiomyopathy and heart transplant recipients: a pilot study: cardiovascular topic.

BACKGROUND: The prevalence of myocarditis and cardiotropic viral infection in human immunodeficiency virus (HIV)-associated cardiomyopathy is unknown in Africa. METHODS: Between April 2002 and December 2007, we compared the prevalence of myocarditis and cardiotropic viral genomes in HIV-associated cardiomyopathy cases with HIV-negative idiopathic dilated cardiomyopathy patients (i.e. negative controls for immunodeficiency) and heart transplant recipients (i.e. positive controls for immunodeficiency) who were seen at Groote Schuur Hospital, Cape Town, South Africa. Myocarditis was sought on endomyocardial biopsy using the imunohistological criteria of the World Heart Federation in 33 patients, 14 of whom had HIV-associated cardiomyopathy, eight with idiopathic dilated cardiomyopathy and 11 heart transplant recipients. RESULTS: Myocarditis was present in 44% of HIV-associated cardiomyopathy cases, 36% of heart transplant recipients, and 25% of participants with idiopathic dilated cardiomyopathy. While myocarditis was acute in 50% of HIV- and heart transplant-associated myocarditis, it was chronic in all those with idiopathic dilated cardiomyopathy. Cardiotropic viral infection was present in all HIV-associated cardiomyopathy and idiopathic dilated cardiomyopathy cases, and in 90% of heart transplant recipients. Multiple viruses were identified in the majority of cases, with HIV-associated cardiomyopathy, heart transplant recipients and idiopathic dilated cardiomyopathy patients having an average of 2.5, 2.2 and 1.1 viruses per individual, respectively. CONCLUSIONS: Acute myocarditis was present in 21% of cases of HIV-associated cardiomyopathy, compared to none of those with idiopathic dilated cardiomyopathy. Infection with multiple cardiotropic viruses may be ubiquitous in Africans, with a greater burden of infection in acquired immunodeficiency states.

The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.

The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin beta1 (Kpnbeta1) and Karyopherin alpha2 (Kpnalpha2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnbeta1 and Kpnalpha2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnbeta1 in cancer cells significantly reduced cell proliferation, while Kpnalpha2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnbeta1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnbeta1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnbeta1 and Kpnalpha2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnbeta1, not Kpnalpha2, induces cancer cell death, making Crm1 and Kpnbeta1 promising candidates as both biomarkers and potential anticancer therapeutic targets.

Glutaraldehyde-induced bowel injury after laparoscopy.

We document the sequelae of the inadvertent introduction of glutaraldehyde into the peritoneal cavity. It describes the clinical course, progressive histological changes to the bowel at different periods over the course of 1 year, and what long-term morbidity remains. The chemical structure, effects, and pathogenesis of glutaraldehyde are described as well as suggestions for avoiding similar problems in the future.

A carboxyl-terminal interaction of lamin B1 is dependent on the CAAX endoprotease Rce1 and carboxymethylation.

The mammalian nuclear lamina protein lamin B1 is posttranslationally modified by farnesylation, endoproteolysis, and carboxymethylation at a carboxyl-terminal CAAX motif. In this work, we demonstrate that the CAAX endoprotease Rce1 is required for lamin B1 endoproteolysis, demonstrate an independent pool of proteolyzed but nonmethylated lamin B1, as well as fully processed lamin B1, in interphase nuclei, and show a role for methylation in the organization of lamin B1 into domains of the nuclear lamina. Deficiency in the endoproteolysis or methylation of lamin B1 results in loss of integrity and deformity of the nuclear lamina. These data show that the organization of the nuclear envelope and lamina is dependent on a mechanism involving the methylation of lamin B1, and they identify a potential mechanism of laminopathy involving a B-type lamin.