Aim-To investigate the role of mast cells in surgical and pathological scar reactions by their identification and quantification using immunohistochemistry. Methods-Surgical scars and pathological scar reactions were stained immunohistochemically for tryptase to identify mast cells. These were quantified in the scar tissue and surrounding dermis. Statistical analyses were performed to test the hypothesis that mast cell numbers were diVerent in the varying types of scar reaction. Results-A significant diVerence was found between the mean number of mast cells in periocular scars compared with keloids, hypertrophic scars, and surgical scars from other sites (p<0.05). No significant diVerence was found in mast cell numbers between the other scar types either within the lesions or surrounding dermis. There were significantly more mast cells in the dermis than in the scar tissue itself, except for the small group of periocular scars. The ratio of mast cells in the lesion compared with the dermis was not significantly diVerent between the scar types, except for the periocular scars. Conclusions-Mast cell numbers are similar in and around keloid, hypertrophic, and surgical scars. The increased number of mast cells at periocular scar sites was contrary to expectation since keloids are rare at this site. Absolute mast cell numbers may not be an accurate measure of tissue concentrations of active mast cell products. Further comparisons between immunological characteristics of keloid and periocular scars may elucidate specific immunological abnormalities of keloid scars, and this has implications for the development of immunotherapy. (Br J Ophthalmol 1998;82:691-694) In adult skin significant dermal damage is repaired by the deposition of connective tissue forming a scar. Fetal skin has greater powers of regeneration and healing without scar formation can occur.1 The majority of scar reactions produce an appropriate amount of connective tissue to fill the dermal defect, but in certain instances excessive fibrous tissue may be deposited leading to the formation of a hypertrophic scar or keloid. These types of pathological scar reactions have many recognised associations and predisposing factors, but the cellular events involved in their formation are not fully established. It has been suggested that mast cells may have an important role in the formation of pathological scar reactions, possibly through the action of IgE.2 Studies have shown that keloids may be associated with increased tissue histamine levels and increased serum IgE.3 Mast cells interact with fibroblasts and are pivotal in the early stages of fibrotic reactions such as fibrosing alveolitis, scleroderma, and wound healing. 4 The liberation of mast cell contents, which include tryptase and histamine, is partly mediated by IgE. Keloid scars are frequently sited on the head and neck, but are rare lesions of the eyelids. [5][6][7] In this study cutaneous mast cells were identified by immunohistochemistry using an antibody to mast cell tryptase and quant...
Background This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. Patients and outcome measures Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses. Results The pCR rates were: overall 55% ( n = 22), HER2-amplified 80% ( n = 12), triple-negative 46% ( n = 7) and HR-positive, HER2-non-amplified 30% ( n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones. Conclusions This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease. Trial registration Clinicaltrials.gov NCT01830244
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