Publications by authors named "Siegal G"

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is an uncommon exuberant form of organizing thrombus that may occur within a vessel, vascular tumor, or hematoma and may change the imaging appearance to mimic an aggressive process. It must be distinguished pathologically from angiosarcoma. They have been most commonly reported within superficial soft tissue tumors, and rapid growth and effect on bone are rarely described.

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Purpose: The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients.

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Proteins can misfold into fibrillar or amorphous aggregates and molecular chaperones act as crucial guardians against these undesirable processes. The BRICHOS chaperone domain, found in several otherwise unrelated proproteins that contain amyloidogenic regions, effectively inhibits amyloid formation and toxicity but can in some cases also prevent non-fibrillar, amorphous protein aggregation. Here, we elucidate the molecular basis behind the multifaceted chaperone activities of the BRICHOS domain from the Bri2 proprotein.

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Introduction: PD-L1 immunohistochemistry (IHC) is being used as a predictive marker of the benefit derived from immunotherapy in several cancer types, including breast cancer. However, the insight gleaned of the prognostic and predictive value of PD-L1 status and its correlation with molecular characteristics during breast cancer progression remains limited.

Methods: We performed an PD-L1 (22C3) assay in pre-treatment primary and metastatic tumor sections from 33 patients with breast carcinoma, matched for post neoadjuvant chemotherapy (p-NACT).

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Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells upon SD can be attributed for the poor outcomes.

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The diagnosis of low-grade fibroblastic/myofibroblastic tumors of acral sites can be challenging. These tumors encompass a diverse group of neoplasms with a spectrum of biologic potential ranges from benign to overtly malignant. They often demonstrate significant clinical, radiologic, and immunophenotypic overlap, in which the molecular phenotype may play an important diagnostic role to arrive at the final diagnosis.

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Compelling data has demonstrated the prognostic significance of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), a subtype generally associated with a poor clinical outcome but highly heterogeneous in nature. There have been limited studies investigating the importance of subsets of T cells in TILs. Further, the significance of intratumoral versus peritumoral TILs remains controversial.

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Introduction: PD-L1 expression is the most widely used predictive marker for immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. However, the current understanding of the association between PD-L1 expression and treatment response is suboptimal. A significant percentage of patients have only a cytological specimen available for clinical management.

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Purpose: Low HER2 expression is emerging as an actionable target for the treatment of breast cancer (BC) with the antibody drug conjugate Trastuzumab deruxtecan. The aim of the study was to characterize the dynamics of HER2 expression during BC progression.

Methods: We evaluated the evolution of HER2 expression in 171 paired primary and metastatic BCs (pBCs/mBCs) by including the HER2-low category.

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Objective: To assess the comparability of international ethics principles and practices used in regulating pediatric research as a first step in determining whether reciprocal deference for international ethics review is feasible. Prior studies by the authors focused on other aspects of international health research, such as biobanks and direct-to-participant genomic research. The unique nature of pediatric research and its distinctive regulation by many countries warranted a separate study.

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Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) have demonstrated antitumor activity in cancers with a homologous recombination deficiency (HRD) and have recently been approved by the FDA for the treatment of germline mutation-associated breast cancer. PARPis have also been found to be efficacious in wild-type () lesions with high genomic loss of heterozygosity (LOH-high). The goal of this study was to retrospectively investigate the tumor mutations in homologous recombination (HRR) genes and the LOH score in advanced-stage breast carcinomas (BCs).

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Periosteal fasciitis is a subtype of nodular fasciitis originating from the periosteum. The diagnosis can be challenging and requires radiologic-pathologic correlation. Advances in molecular analysis confirmed that nodular fasciitis and its related lesions harbor a gene rearrangement with one of the several potential partners.

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Ewing sarcoma (ES) can be confirmed by identifying the fusion transcript. This study is to investigate whether immunostaining (IHC) of PRKCB-a protein directly regulated by is a surrogate maker for diagnosing ES in routine practice. Microarray gene expression analyses were conducted.

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Background: While most estrogen receptor-positive (ER+) breast cancers express progesterone receptor (PR), a small subset of tumors exhibits an ER+/PR- phenotype despite the fact that PR is an ER-dependent gene product. Previous studies have shown that these tumors are generally associated with a worse clinical outcome when compared to the ER+/PR+ breast cancers, indicating that they are clinically and probably genetically different entities.

Methods: We characterized the clinicopathologic features of ER+/PR- tumors from the Surveillance, Epidemiology and End Results (SEER) database and the authors' institutional cohort.

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Introduction: Gene fusion identification by RNA-based next-generation sequencing (NGS) provides important information for cancer patients. NGS is commonly initiated by treating oncologists to identify therapeutic options. However, the implications of large fusion panels on tumor classification and diagnosis are underappreciated.

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Tenosynovial giant cell tumors typically arise in the synovium of joints, bursae, or tendon sheaths. They may occur in an intra- or extra-articular location and can be divided into localized and diffuse types. The neoplastic nature of the lesion has been supported by a recurrent gene rearrangement in a small subset of lesional cells, of which the most common fusion partner is .

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Gene knockout of the master regulator of mitochondrial fission, Drp1, prevents neoplastic transformation. Also, mitochondrial fission and its opposing process of mitochondrial fusion are emerging as crucial regulators of stemness. Intriguingly, stem/progenitor cells maintaining repressed mitochondrial fission are primed for self-renewal and proliferation.

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Myoepithelial tumors arising in soft tissue are uncommon and mostly manifest a benign clinical course, although a malignant form does exist. An EWSR1 gene rearrangement is a common event in these tumors. Ossifying fibromyxoid tumor, a rare soft tissue neoplasm of uncertain differentiation, may have overlapping histologic and immunophenotypic features with myoepithelial tumors, but frequently harbors a PHF1 gene rearrangement.

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There have been many breast cancer prognostic models proposed in the last few decades, varying in their methods of development and validation, predictors, outcomes, and patients included. Most models were developed to assess prognostic outcomes for early breast cancers. In this study, we established a simplified prognostic score to predict survival outcomes in all breast cancer patients.

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Background: Human epidermal growth factor 2 (HER2) amplification and/or overexpression occurs in 12% to 25% of breast cancers. Accurate detection of HER2 is critical in predicting response to HER2-targeted therapy. Both immunohistochemistry (IHC) and in situ hybridization (ISH) are FDA-approved methods for detecting HER2 status because its protein overexpression is largely attributable to gene amplification.

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Context.—: A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically been thought to be reactive lesions. However, modern molecular techniques when supplementing clinical, radiographic, and histologic evaluation suggest they may, in fact, be neoplasms.

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