Despite reports of sex steroid receptor and COX 2 expression in desmoid‐type fibromatosis, responses to single agent therapy with anti‐estrogens and non‐steroidal anti‐inflammatory drugs are unpredictable. Perhaps combination pharmacotherapy might be more effective in desmoid tumors that co‐express these targets. Clearly, further understanding of the signaling pathways deregulated in desmoid tumors is essential for the development of targeted molecular therapy. Transforming growth factor–β ( TGF β) and bone morphogenetic proteins ( BMP ) are important regulators of fibroblast proliferation and matrix deposition, but little is known about the TGF β superfamily in fibromatosis. A tissue microarray representing 27 desmoid tumors was constructed; 14 samples of healing scar and six samples of normal fibrous tissue were included for comparison. Expression of selected receptors and activated downstream transcription factors of TGF β family signaling pathways, β–catenin, sex steroid hormone receptors and COX 2 were assessed using immunohistochemistry; patterns of co–expression were explored via correlational statistical analyses. In addition to β–catenin, immunoreactivity for phosphorylated SMAD 2/3 (indicative of active TGF β signaling) and COX 2 was significantly increased in desmoid tumors compared with healing scar and quiescent fibrous tissue. Low levels of phosphorylated SMAD 1/5/8 were detected in only a minority of cases. Transforming growth factor–β receptor type 1 and androgen receptor were expressed in both desmoid tumors and scar, but not in fibrous tissue. Estrogen receptor–β was present in all cases studied. Transforming growth factor–β signaling appears to be activated in desmoid‐type fibromatosis and phosphorylated SMAD 2/3 and COX 2 immunoreactivity might be of diagnostic utility in these tumors. Given the frequency of androgen receptor, estrogen receptor–β and COX 2 co‐expression in desmoid tumors, further assessment of the efficacy of combination pharmacotherapy using hormonal agonists/antagonists together with COX 2 inhibitors should be considered.
Case: We report the case of a 14-year-old girl with an aneurysmal bone cyst of the scaphoid successfully treated with curettage, phenol adjuvant therapy, and bone-grafting. Conclusion: Aneurysmal bone cysts rarely arise in the carpal bones, especially the scaphoid. This lesion may represent a rare yet treatable cause of wrist dysfunction in some patients. Curettage, phenol adjuvant therapy, and bone-grafting resulted in a good clinical outcome for our patient.
Abstract Background Most prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown that nuclear factor I/B (NFIB) regulates AR activity in androgen-dependent prostate cancer cells in vitro . However, the status of NFIB in prostate cancer was unknown. Methods We immunostained a tissue microarray including normal, hyperplastic, prostatic intraepithelial neoplasia, primary prostatic adenocarcinoma, and castration-resistant prostate cancer tissue samples for NFIB, AR, and synaptophysin, a marker of neuroendocrine differentiation. We interrogated publically available data sets in cBioPortal to correlate NFIB expression and AR and neuroendocrine prostate cancer (NEPCa) activity scores. We analyzed prostate cancer cell lines for NFIB expression via Western blotting and used nuclear and cytoplasmic fractionation to assess where NFIB is localized. We performed coimmunoprecipitation studies to determine if NFIB and AR interact. Results NFIB increased in the nucleus and cytoplasm of prostate cancer samples versus matched normal controls, independent of Gleason score. Similarly, cytoplasmic AR and synaptophysin increased in primary prostate cancer. We observed strong NFIB staining in primary small cell prostate cancer. The ratio of cytoplasmic-to-nuclear NFIB staining was predictive of earlier biochemical recurrence in prostate cancer, once adjusted for tumor margin status. Cytoplasmic AR was an independent predictor of biochemical recurrence. There was no statistically significant difference between NFIB and synaptophysin expression in primary and castration-resistant prostate cancer, but cytoplasmic AR expression was increased in castrationresistant samples. In primary prostate cancer, nuclear NFIB expression correlated with cytoplasmic NFIB and nuclear AR, while cytoplasmic NFIB correlated with synaptophysin, and nuclear and cytoplasmic AR. In castration-resistant prostate cancer samples, NFIB expression correlated positively with an AR activity score, and negatively with the NEPCa score. In prostate cancer cell lines, NFIB exists in several isoforms. We observed NFIB predominantly in the nuclear fraction of prostate cancer cells with increased cytoplasmic expression seen in castration-resistant cell lines. We observed an interaction between AR and NFIB through coimmunoprecipitation experiments. Conclusion We have described the expression pattern of NFIB in primary and castrationresistant prostate cancer and its positive correlation with AR. We have also demonstrated AR interacts with NFIB.
Abstract Rhabdomyosarcomas are the most common soft tissue sarcoma in children and adolescents, but some specific histologic subtypes occur in adult patients. They involve various soft tissue or visceral sites, and most follow an aggressive clinical course. Currently, rhabdomyosarcomas are classified into 4 distinct clinical and morphological subtypes: embryonal, alveolar, spindle cell/sclerosing, and pleomorphic. This article reviews the clinical, histopathologic, and updated genetic features of these rhabdomyosarcoma subtypes.
Neurogenic tumors are an uncommon yet important category of soft tissue tumors in children and adolescents because of their frequent association with various genetic syndromes. The heterogeneous cellular composition of the peripheral nerve and the wide metaplastic capacity of the neural crest and its derivatives generate a variety of neoplasms with neurogenic differentiation. This article reviews the clinicopathologic features and differential diagnosis of neurogenic tumors in the first two decades of life, and highlights use of selected ancillary methods for diagnosis.
Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis.Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif.Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels.Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology.
