Pediatric Soft Tissue Tumors With BCOR ITD Express EGFR but Not OLIG2

2020 ◽  
Vol 23 (6) ◽  
pp. 424-430
Author(s):  
Claudia M. Salgado ◽  
Angelica Zin ◽  
Marta Garrido ◽  
Irina Kletskaya ◽  
Rita DeVito ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Growth Factor Receptor ◽  
Soft Tissue Tumors ◽  
Cell Of Origin ◽  
Mesenchymal Tumors ◽  
Internal Tandem Duplication ◽  
Egfr Amplification ◽  
Egfr Expression ◽  
Epidermal Growth

Introduction Somatic internal tandem duplication of 3’ of BCOR ( BCOR ITD) has been found in clear cell sarcomas of the kidney (CCSK), soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and a subgroup of central nervous system high-grade neuroepithelial tumors (CNS-HGNET). BCOR ITD+ tumors share morphologic features. Expression of OLIG2 and epidermal growth factor receptor (EGFR) has been reported in CNS-HGNET with BCOR ITD. Here, we characterize OLIG2 and EGFR expression in URCS/PMMTI with BCOR ITD. Methods Paraffin blocks of 9 polymerase chain reaction-confirmed soft tissue BCOR ITD+ tumors (URCS/PMMTI) were immunophenotyped for OLIG2 and EGFR expression and scored semiquantitatively by percentage of positive cells and intensity of staining as negative, 1+, 2+, and 3+. Fluorescence in situ hybridization (FISH) for EGFR amplification was performed (amplification EGFR/CEP7 ratio ≥2.0). Results All 9 tumors showed membrane/cytoplasmic expression of EGFR, strong and diffuse (3+) in 8 cases; weak (+2) in 1. FISH detected no EGFR amplification. OLIG2 was negative in all. Conclusions EGFR is overexpressed in pediatric URCS/PMMTI with BCOR ITD and may be related to transcriptional upregulation of EGFR by BCOR ITD. OLIG2 negative staining differentiates URCS/PMMTI from CNS-HGNET. This finding may further support the possibility that these tumors have a different stem cell of origin.

scholarly journals Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs

Sarcoma ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Séverine Tabone-Eglinger ◽  
Radislav Bahleda ◽  
Jean-François Côté ◽  
Philippe Terrier ◽  
Dominique Vidaud ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Survivin Expression ◽  
Neurofibromatosis Type ◽  
High Grade ◽  
Rt Pcr ◽  
Ki 67 ◽  
Egfr Expression ◽  
Epidermal Growth

Malignant peripheral nerve sheath tumours (MPNSTs) are highly malignant and resistant. Transformation might implicate up regulation of epidermal growth factor receptor (EGFR). Fifty-two MPNST samples were studied for EGFR, Ki-67, p53, and survivin expression by immunohistochemistry and forEGFRamplification by in situ hybridization. Results were correlated with clinical data.EGFRRNA was also quantified by RT-PCR in 20 other MPNSTs and 14 dermal neurofibromas. Half of the patients had a neurofibromatosis type 1 (NF1). EGFR expression, detected in 86% of MPNSTs, was more frequent in NF1 specimens and closely associated with high-grade and p53-positive areas. MPNSTs expressed moreEGFRtranscripts than neurofibromas. No amplification ofEGFRlocus was observed. NF1 status was the only prognostic factor in multivariate analysis, with median survivals of 18 and 43 months for patients with or without NF1. Finally, EGFR might become a new target for MPNSTs treatment, especially in NF1-associated MPNSTs.

Glioblastomas in the Older Old

2005 ◽  
Vol 129 (5) ◽  
pp. 624-631 ◽  
Author(s):  
B. K. Kleinschmidt-DeMasters ◽  
K. O. Lillehei ◽  
M. Varella-Garcia
Keyword(s):  
Cell Cycle ◽  
Survival Data ◽  
Growth Factor Receptor ◽  
Chromosome 7 ◽  
Tissue Samples ◽  
Old Patients ◽  
Egfr Amplification ◽  
Epidermal Growth ◽  
Mib 1

Abstract Context.—Recent studies have identified fundamental biological differences in the effects of epidermal growth factor receptor (EGFR) amplification on survival in older versus younger patients with glioblastoma multiforme (GBM). Cell cycle labeling indices have also been found to be inordinately high in older GBM patients and may contribute to the known adverse prognosis in this cohort. However, testing has not been conducted on significant numbers of patients of very advanced age, in whom these features might be expected to emerge as even more significant factors. Objective.—To assess EGFR amplification status and MIB-1 indices in patients with GBM who are older than 75 years. Design.—We identified 20 patients (female-male ratio, 11:9; 11 aged 75–79 years and 9 aged 80–87 years) and studied tumor tissue samples with immunohistochemistry for cell cycle labeling index and by fluorescence in situ hybridization for EGFR amplification. Survival data were obtained from the Colorado Tumor Registry. Results.—Mean MIB-1 index was high (24.8%), but individual indices did not correlate with survival. EGFR amplification was detected in 25% of cases, with gain of chromosome 7 in all but one of the remaining patients. Ninety-five percent of patients manifested EGFR amplification and/or polysomy of chromosome 7. Heterogeneity was found within a given tumor, with 10% to 60% of cells showing gain of chromosome 7. Overall patient survival was poor (mean, 4.6 months), but was significantly longer in those with EGFR gene amplification (mean, 8.3 months; median, 10.5 months) versus those without (mean, 3.2 months; median, 2.0 months) (P = .04). Conclusion.—The presence of EGFR amplification is a significant predictor of survival time in older old patients.

Analysis of PTEN, BRAF, and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer

2009 ◽  
Vol 27 (35) ◽  
pp. 5924-5930 ◽  
Author(s):  
Pierre Laurent-Puig ◽  
Anne Cayre ◽  
Gilles Manceau ◽  
Emmanuel Buc ◽  
Jean-Baptiste Bachet ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Metastatic Colon Cancer ◽  
Wild Type ◽  
Braf Mutations ◽  
Allelic Discrimination ◽  
Egfr Amplification ◽  
Epidermal Growth

Purpose The occurrence of KRAS mutation is predictive of nonresponse and shorter survival in patients treated by anti–epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors. However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy. Patients and Methods We retrospectively collected tumors from 173 patients with mCRC. All but one patient received a cetuximab-based regimen as second-line or greater therapy. KRAS and BRAF status were assessed by allelic discrimination. EGFR amplification was assessed by chromogenic in situ hybridization and fluorescent in situ hybridization, and the expression of PTEN was assessed by immunochemistry. Results In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = .063) but were strongly associated with shorter progression-free survival (P < .001) and shorter overall survival (OS; P < .001). A high EGFR polysomy or an EGFR amplification was found in 17.7% of the patients and was associated with response (P = .015). PTEN null expression was found in 19.9% of the patients and was associated with shorter OS (P = .013). In multivariate analysis, BRAF mutation and PTEN expression status were associated with OS. Conclusion BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.

EGFR Overexpression and Sequence Analysis of KRAS, BRAF, and EGFR Mutation Hot Spots in Canine Intestinal Adenocarcinoma

2021 ◽  
pp. 030098582110097
Author(s):  
Seung-Hee Cho ◽  
Byung-Joon Seung ◽  
Soo-Hyeon Kim ◽  
Min-Kyung Bae ◽  
Ha-Young Lim ◽  
...  
Keyword(s):  
Hot Spots ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Mrna Levels ◽  
Mutation Status ◽  
In Situ Carcinoma ◽  
Egfr Expression ◽  
Rna In Situ Hybridization ◽  
Epidermal Growth

Epidermal growth factor receptor (EGFR) is overexpressed in many human colorectal cancers and anti-EGFR agents are employed as immunotherapies. However, KRAS, EGFR, and BRAF gene mutations can influence the activity of the anti-EGFR agents. We evaluated EGFR expression at protein and mRNA levels in canine intestinal adenocarcinomas using immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH). We also investigated the mutation status of EGFR, KRAS, and BRAF to aid the development of anti-EGFR agents for canine intestinal adenocarcinoma. EGFR expression was highest in adenocarcinoma, followed by intramucosal neoplasia (adenoma and in situ carcinoma), and nonneoplastic canine intestinal tissue, at both protein ( P = .000) and mRNA ( P = .005) levels. The EGFR, KRAS, and BRAF genes showed wild-type sequences at the mutation hot spots in all 13 specimens. Thus, EGFR might serve as a promising diagnostic marker in canine intestinal adenocarcinoma, and further studies would be needed to develop EGFR-targeted anticancer therapies.

scholarly journals Updated Insights on EGFR Signaling Pathways in Glioma

2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Egfr Signaling ◽  
Current Standard ◽  
Egfr Amplification ◽  
Epidermal Growth ◽  
New Diagnosis ◽  
Clear Clinical Benefit

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

Not All Cases of Mammary Paget’s Disease are Cytokeratin-7 Positive: A Challenging Diagnosis!

2021 ◽  
pp. 106689692110029
Author(s):  
Kerschen Anja ◽  
Dano Hélène ◽  
Van Eeckhout Pascal ◽  
Marot Liliane ◽  
Van Bockstal Mieke
Keyword(s):  
Present Report ◽  
Paget’S Disease ◽  
Growth Factor Receptor ◽  
Punch Biopsy ◽  
Paget's Disease ◽  
Cytokeratin 7 ◽  
In Situ Carcinoma ◽  
Epidermal Growth ◽  
Mammary Paget’S Disease

Mammary Paget’s disease accounts for 1% to 3% of all breast tumors and manifests as a chronic eczematous lesion of the areolar skin. It can occur without any underlying neoplasia or can be present in association with an underlying invasive and/or in situ carcinoma of the breast. The present report describes a challenging nipple punch biopsy showing an infiltration of the lower third to two-thirds of the epidermis by large, ovoid, neoplastic cells. The morphology was consistent with mammary Paget's disease, although immunohistochemistry for cytokeratin-7 (CK7) was repeatedly negative. This resulted in an initial misdiagnosis and, subsequently, a delay in the patient's follow-up. Additional immunohistochemistry for GATA binding protein 3 (GATA3) and human epidermal growth factor receptor 2 (HER2), as well as a second opinion of a breast pathologist, resulted in the diagnosis of mammary Paget's disease. The aim of this article is to raise awareness among pathologists and prevent them from misdiagnosing CK7-negative Paget disease of the breast.

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