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Cancers May 2024The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing;...
The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.
PubMed: 38791952
DOI: 10.3390/cancers16101874 -
Journal of Cancer Research and... Apr 2024Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common... (Review)
Review
Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.
Topics: Humans; Chondrosarcoma; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Bone Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy
PubMed: 38687921
DOI: 10.4103/jcrt.jcrt_2269_23 -
Oncology Letters Jun 2024Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of...
Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×10 PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).
PubMed: 38638849
DOI: 10.3892/ol.2024.14377 -
Cureus Feb 2024Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment...
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment for patients with advanced GISTs include both surgical resection and imatinib therapy. There have been cases that document the alterations of patients' GIST histomorphology both with primary GIST prior to imatinib therapy and with recurrent GIST after imatinib therapy. However, there has been no documented case of a patient who has recurrent GIST with chondroid differentiation at the primary site after imatinib therapy. In this article, we report an incidental finding of a 58-year-old patient who had two treatments of imatinib therapy prior to surgical resection of her recurrent GIST in her stomach. We also explore through a mini-literature review the various cases of GIST with chondroid differentiation that have been reported to compare the histomorphology, immunophenotype, and patient demographic of these cases. This article is significant for reporting a rare finding of GIST after imatinib therapy and highlights the various presentations that GIST could acquire after imatinib therapy that exclude another malignant process, such as chondrosarcoma.
PubMed: 38533168
DOI: 10.7759/cureus.54842 -
Indian Journal of Pathology &... Jul 2023
PubMed: 38391341
DOI: 10.4103/ijpm.ijpm_299_22 -
Oxford Medical Case Reports Feb 2024Uterine carcinosarcoma (UCS), also known as malignant mixed Müllerian tumor, is a rare malignancy, which consists of both carcinomatous and sarcomatous elements, with a...
Uterine carcinosarcoma (UCS), also known as malignant mixed Müllerian tumor, is a rare malignancy, which consists of both carcinomatous and sarcomatous elements, with a clinical picture resembling endometrial carcinoma. We report a case of a 74-year-old woman is reported with UCS, diagnosed after a 7 months history of vaginal bleeding and abdominal pain. Previous transvaginal sonography showed nonspecific findings, but a repeated one revealed a central uterine mass. Dilatation and curettage and several biopsies were performed. The initial histological report suggested high-grade endometrial stromal sarcoma. After total hysterectomy with salpingo-oophorectomy, pathology confirmed UCS whose sarcomatous element was heterologous type included osteosarcoma and chondrosarcoma. The patient is receiving adjuvant chemotherapy. This case highlights the importance of pathology evaluation after hysterectomy to raise the confidence of diagnosis with emphasis on prognostic outcomes that can be significantly affected in patients with this type of sarcomatous element.
PubMed: 38370501
DOI: 10.1093/omcr/omad157 -
International Journal of Molecular... Feb 2024Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is...
Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. is a 'promiscuous' gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3' partners, and , which have not been previously reported. may functionally replace , the usual 3' partner in extraskeletal myxoid chondrosarcoma. The third GF, , has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting.
Topics: Humans; Calmodulin-Binding Proteins; Chondrosarcoma; Neoplasms, Connective and Soft Tissue; Oncogene Proteins, Fusion; RNA-Binding Protein EWS; RNA-Binding Proteins; Sarcoma; Soft Tissue Neoplasms
PubMed: 38339014
DOI: 10.3390/ijms25031735