Incidence of Her2/neu receptor positive results in breast cancer cases in Al-Yarmouk teaching hospital

Back ground: Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death in women. HER2 is a transmembrane receptor with tyrosine kinase. It belongs to a family of four receptors (EGFR/HER1, HER2, HER3, HER4) that are involved in regulating cell growth, survival and differentiation. Structural studies revealed that HER2 is always in an active conformation and ready to interact with the ligand-activated HER receptors, before the advent of HER2-directed therapies, this increased level of HER2 was associated with high recurrence rates and increased mortality in patients with node-positive and node-negative disease. Aim of study: To calculate the incidence of human epidermal growth factor receptor 2 positive results in addition to its relation to estrogen receptor and progesterone receptor results in breast cancer cases in AL-Yarmouk teaching hospital and compare our results to regional and international results. Patients and Methods: Analysis of a prospectively collected clinical database was performed. We included 40 patients who had mastectomy for stage one to stage three breast cancer cases, from October 2018 to October 2019, where by complete receptor information were done. Fluorescence in Situ Hybridization test had been requested. The corresponding H&E-stained slides from all cases were reviewed. Unstained tissue sections containing tumor, as well as adjacent normal breast parenchyma when possible and corresponding to those used for the Fluorescence In Situ Hybridization test were selected from each case for immunohistochemical staining, comparison with regional and international results was done. Results: Total number of cases collected was 40 cases of breast cancer; they were investigated for human epidermal growth factor receptors 2 in addition to estrogen and progesterone receptors. Age of the patients ranged from 30 to 69 years (mean, 49.27 years). HER2/ neu positive cases were (8) (20%) of cases, and negative cases were (32) (80%), in addition to a statically significant relation to ER and PR receptor results. Conclusion: The incidence of human epidermal growth factor receptors 2 positive at AL-Yarmouk teaching hospital was 20%, estrogen receptors \ progesterone receptors positive was (57.5%) and the relation between these receptors was statistically significant.

Incidence of Her2/neu receptor positive results in breast cancer cases in Al-Yarmouk teaching hospital

Back ground: Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death in women. HER2 is a transmembrane receptor with tyrosine kinase. It belongs to a family of four receptors (EGFR/HER1, HER2, HER3, HER4) that are involved in regulating cell growth, survival and differentiation. Structural studies revealed that HER2 is always in an active conformation and ready to interact with the ligand-activated HER receptors, before the advent of HER2-directed therapies, this increased level of HER2 was associated with high recurrence rates and increased mortality in patients with node-positive and node-negative disease. Aim of study: To calculate the incidence of human epidermal growth factor receptor 2 positive results in addition to its relation to estrogen receptor and progesterone receptor results in breast cancer cases in AL-Yarmouk teaching hospital and compare our results to regional and international results. Patients and Methods: Analysis of a prospectively collected clinical database was performed. We included 40 patients who had mastectomy for stage one to stage three breast cancer cases, from October 2018 to October 2019, where by complete receptor information were done. Fluorescence in Situ Hybridization test had been requested. The corresponding H&E-stained slides from all cases were reviewed. Unstained tissue sections containing tumor, as well as adjacent normal breast parenchyma when possible and corresponding to those used for the Fluorescence In Situ Hybridization test were selected from each case for immunohistochemical staining, comparison with regional and international results was done. Results: Total number of cases collected was 40 cases of breast cancer; they were investigated for human epidermal growth factor receptors 2 in addition to estrogen and progesterone receptors. Age of the patients ranged from 30 to 69 years (mean, 49.27 years). HER2/ neu positive cases were (8) (20%) of cases, and negative cases were (32) (80%), in addition to a statically significant relation to ER and PR receptor results. Conclusion: The incidence of human epidermal growth factor receptors 2 positive at AL-Yarmouk teaching hospital was 20%, estrogen receptors \ progesterone receptors positive was (57.5%) and the relation between these receptors was statistically significant.

Unusual Presentations of Eccrine Porocarcinomas

Eccrine porocarcinomas (EPCs) are rare tumours, albeit the most common malignant adnexal tumours of the skin. They can present with very heterogeneous clinical and dermoscopic features, rendering diagnosis limited to histopathological examination alone. We share 2 cases of EPCs, one of which arose in a patient with a prior diagnosis of cutaneous squamous cell carcinoma (SCC) and another whose EPC was likely a malignant transformation of an existing poroma. An occurrence of porocarcinoma after the diagnosis of SCC may suggest the possibility of unknown risk factors for both. Positivity to androgen, oestrogen, and epidermal growth factor receptors was seen in a proportion of porocarcinomas, and this may prompt further research on combination therapy between conventional treatment modalities with hormone receptor antagonists. Malignant change of a poroma may be a more common phenomenon than we would expect based on the current literature.

Dose predictions for [177Lu]Lu-DOTA-panitumumab F(ab′)2 in NRG mice with HNSCC patient-derived tumour xenografts based on [64Cu]Cu-DOTA-panitumumab F(ab′)2 – implications for a PET theranostic strategy

Background Epidermal growth factor receptors (EGFR) are overexpressed on many head and neck squamous cell carcinoma (HNSCC). Radioimmunotherapy (RIT) with F(ab')2 of the anti-EGFR monoclonal antibody panitumumab labeled with the β-particle emitter, 177Lu may be a promising treatment for HNSCC. Our aim was to assess the feasibility of a theranostic strategy that combines positron emission tomography (PET) with [64Cu]Cu-DOTA-panitumumab F(ab')2 to image HNSCC and predict the radiation equivalent doses to the tumour and normal organs from RIT with [177Lu]Lu-DOTA-panitumumab F(ab')2. Results Panitumumab F(ab')2 were conjugated to DOTA and complexed to 64Cu or 177Lu in high radiochemical purity (95.6 ± 2.1% and 96.7 ± 3.5%, respectively) and exhibited high affinity EGFR binding (Kd = 2.9 ± 0.7 × 10− 9 mol/L). Biodistribution (BOD) studies at 6, 24 or 48 h post-injection (p.i.) of [64Cu]Cu-DOTA-panitumumab F(ab')2 (5.5–14.0 MBq; 50 μg) or [177Lu]Lu-DOTA-panitumumab F(ab')2 (6.5 MBq; 50 μg) in NRG mice with s.c. HNSCC patient-derived xenografts (PDX) overall showed no significant differences in tumour uptake but modest differences in normal organ uptake were noted at certain time points. Tumours were imaged by microPET/CT with [64Cu]Cu-DOTA-panitumumab F(ab')2 or microSPECT/CT with [177Lu]Lu-DOTA-panitumumab F(ab')2 but not with irrelevant [177Lu]Lu-DOTA-trastuzumab F(ab')2. Tumour uptake at 24 h p.i. of [64Cu]Cu-DOTA-panitumumab F(ab')2 [14.9 ± 1.1% injected dose/gram (%ID/g) and [177Lu]Lu-DOTA-panitumumab F(ab')2 (18.0 ± 0.4%ID/g) were significantly higher (P < 0.05) than [177Lu]Lu-DOTA-trastuzumab F(ab')2 (2.6 ± 0.5%ID/g), demonstrating EGFR-mediated tumour uptake. There were no significant differences in the radiation equivalent doses in the tumour and most normal organs estimated for [177Lu]Lu-DOTA-panitumumab F(ab')2 based on the BOD of [64Cu]Cu-DOTA-panitumumab F(ab')2 compared to those estimated directly from the BOD of [177Lu]Lu-DOTA-panitumumab F(ab')2 except for the liver and whole body which were modestly underestimated by [64Cu]Cu-DOTA-panitumumab F(ab')2. Region-of-interest (ROI) analysis of microPET/CT images provided dose estimates for the tumour and liver that were not significantly different for the two radioimmunoconjugates. Human doses from administration of [177Lu]Lu-DOTA-panitumumab F(ab')2 predicted that a 2 cm diameter HNSCC tumour in a patient would receive 1.1–1.5 mSv/MBq and the whole body dose would be 0.15–0.22 mSv/MBq. Conclusion A PET theranostic strategy combining [64Cu]Cu-DOTA-panitumumab F(ab')2 to image HNSCC tumours and predict the equivalent radiation doses in the tumour and normal organs from RIT with [177Lu]Lu-DOTA-panitumumab F(ab')2 is feasible. RIT with [177Lu]Lu-DOTA-panitumumab F(ab')2 may be a promising approach to treatment of HNSCC due to frequent overexpression of EGFR.

Novel miRNA Targets and Therapies in the Triple-Negative Breast Cancer Microenvironment: An Emerging Hope for a Challenging Disease

Treatment of triple-negative breast cancer (TNBC) remains challenging because of the heterogeneity of the disease and lack of single targetable driving mutations. TNBC does not rely on estrogen, progesterone or epidermal growth factor receptors and is associated with aggressive disease progression and poor prognosis. TNBC is also characterized by resistance to chemotherapeutics, and response to immunotherapies is limited despite promising results in a subset of TNBC patients. MicroRNAs (miRNAs) have emerged as significant drivers of tumorigenesis and tumor progression in triple-negative breast cancer (TNBC) and present unique opportunities to target various components of the TNBC microenvironment for improved efficacy against this difficult to treat cancer. Effects of miRNAs on multiple targets may improve response rates in the context of this genetically and biologically heterogeneous disease. In this review, we offer a comprehensive view of miRNA regulation in TNBC, treatment challenges presented by TNBC in the context of the tumor microenvironment and stem cell subpopulations, and current and emerging miRNA-based therapeutic strategies targeting various components of the TNBC microenvironment. In addition, we offer insight into novel targets that have potential for treating TNBC through multiple mechanisms in the tumor microenvironment simultaneously and those that may be synergistic with standard chemotherapies.

Airway Epithelial Dysfunction in Asthma: Relevant to Epidermal Growth Factor Receptors and Airway Epithelial Cells

Airway epithelium plays an important role as the first barrier from external pathogens, including bacteria, viruses, chemical substances, and allergic components. Airway epithelial cells also have pivotal roles as immunological coordinators of defense mechanisms to transfer signals to immunologic cells to eliminate external pathogens from airways. Impaired airway epithelium allows the pathogens to remain in the airway epithelium, which induces aberrant immunological reactions. Dysregulated functions of asthmatic airway epithelium have been reported in terms of impaired wound repair, fragile tight junctions, and excessive proliferation, leading to airway remodeling, which contributes to aberrant airway responses caused by external pathogens. To maintain airway epithelium integrity, a family of epidermal growth factor receptors (EGFR) have pivotal roles in mechanisms of cell growth, proliferation, and differentiation. There are extensive studies focusing on the relation between EGFR and asthma pathophysiology, which describe airway remodeling, airway hypermucus secretion, as well as immunological responses of airway inflammation. Furthermore, the second EGFR family member, erythroblastosis oncogene B2 (ErbB2), has been recognized to be involved with impaired wound recovery and epithelial differentiation in asthmatic airway epithelium. In this review, the roles of the EGFR family in asthmatic airway epithelium are focused on to elucidate the pathogenesis of airway epithelial dysfunction in asthma.