Nuclear EGFR Expression Is Associated With Poor Survival in Laryngeal Carcinoma

Marijić, Blažen; Braut, Tamara; Babarović, Emina; Krstulja, Mira; Maržić, Diana; Avirović, Manuela; Kujundžić, Milodar; Hadžisejdić, Ita

doi:10.1097/pai.0000000000000932

Cited by 12 publications

(13 citation statements)

References 33 publications

(82 reference statements)

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“…A correlation between nuclear EGFR expression and HNSCC clinical parameters has also been reported by several authors. In a study on laryngeal HNSCC, a higher frequency of strong nuclear EGFR was found in invasive tumors compared to laryngeal dysplasia and vocal cord polyps, and high nuclear EGFR expression levels correlated with worse overall cancer patients’ survival ( 39 ). In oropharyngeal HNSCC high nuclear EGFR expression levels were associated with reduced responses to radiation therapy, higher risk of local recurrence and lower overall survival ( 99 , 100 ).…”

Section: Involvement Of Non-canonical Erbb Signaling In Hnsccmentioning

confidence: 99%

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

et al. 2023

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type, has often an aggressive course and is poorly responsive to current therapeutic approaches, so that 5-year survival rates for patients diagnosed with advanced disease is lower than 50%. The Epidermal Growth Factor Receptor (EGFR) has emerged as an established oncogene in HNSCC. Indeed, although HNSCCs are a heterogeneous group of cancers which differ for histological, molecular and clinical features, EGFR is overexpressed or mutated in a percentage of cases up to about 90%. Moreover, aberrant expression of the other members of the ErbB receptor family, ErbB2, ErbB3 and ErbB4, has also been reported in variable proportions of HNSCCs. Therefore, an increased expression/activity of one or multiple ErbB receptors is found in the vast majority of patients with HNSCC. While aberrant ErbB signaling has long been known to play a critical role in tumor growth, angiogenesis, invasion, metastatization and resistance to therapy, more recent evidence has revealed its impact on other features of cancer cells’ biology, such as the ability to evade antitumor immunity. In this paper we will review recent findings on how ErbB receptors expression and activity, including that associated with non-canonical signaling mechanisms, impacts on prognosis and therapy of HNSCC.

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Section: Involvement Of Non-canonical Erbb Signaling In Hnsccmentioning

confidence: 99%

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

et al. 2023

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“…For head and neck tumors, numerous diagnostic and prognostic markers have been investigated in clinical studies, but their clinical significance remains questionable [ 5 , 22 ]. Recent discoveries related to a completely new way of regulating cell proliferation and apoptosis through the independent action of EGFR in the nucleus of numerous tumors, such as ovarian, breast, oropharyngeal, laryngeal, and esophageal carcinoma, have been the basis for studying premalignant and malignant changes in the oral cavity, where the role of this receptor had not been previously elucidated [ 8 , 11 , 12 , 13 , 14 , 15 , 16 ]. In addition to nEGFR, we also analyzed the expression of markers of cell cycle and proliferation (Ki-67, cyclin D1, p53, mEGFR) and markers of tumor stem cells (ABCG2) involved in oral carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies suggest that EGF, H2O2, UV radiation, therapeutic agents, and ionizing radiation may cause translocation of EGFR to the nucleus, where nuclear EGFR (nEGFR) interacts with various transcription factors (cyclin D1, ABCG2/BCRP, Aurora kinase A, COX-2, gene regulator c-Myc, iNOS) and acts on the activation of numerous genes involved in cell proliferation, tumor progression, and DNA repair [ 7 , 8 , 9 , 10 ]. Available literature indicates that overexpression of nEGFR in ovarian, breast, oropharyngeal, laryngeal, and esophageal cancers negatively affects disease prognosis and resistance to radiotherapy and chemotherapy, whereas its role in oral malignancies has not yet been investigated [ 8 , 11 , 12 , 13 , 14 , 15 , 16 ]. The above only confirms the complexity and scope of the network of signaling pathways mediated by EGFR activation that play an important role in cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma

Tarle

Raguž

Müller

et al. 2023

IJMS

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The aim of this study was to determine, by immunohistochemical methods, the expression of nEGFR and markers of cell proliferation (Ki-67), cell cycle (mEGFR, p53, cyclin D1), and tumor stem cells (ABCG2) in 59 pathohistological samples of healthy oral mucosa, 50 oral premalignant changes (leukoplakia and erythroplakia), and 52 oral squamous cell carcinomas (OSCC). An increase in the expression of mEGFR and nEGFR was found with the development of the disease (p < 0.0001). In the group of patients with leukoplakia and erythroplakia, we found a positive correlation between nEGFR and Ki67, p53, cyclin D1, and mEGFR, whereas in the group of patients with OSCC, we found a positive correlation between nEGFR and Ki67, mEGFR (p < 0.05). Tumors without perineural (PNI) invasion had a higher expression of p53 protein than tumors with PNI (p = 0.02). Patients with OSCC and overexpression of nEGFR had shorter overall survival (p = 0.004). The results of this study suggest a potentially important independent role of nEGFR in oral carcinogenesis.

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“…18,30,31 However, the particular attention of scientists has been attracted by its overexpression in tumor tissues of the ovary, breast, larynx, oropharyngeal carcinoma, and squamous cell carcinoma of the esophagus, where it has been shown to negatively affect survival. 18,22,[32][33][34] Taguchi found nEGFR expression in 28% of patients with tongue squamous cell carcinoma, but without correlation with clinicopathologic factors. 35 The effect of nEGFR expression in OPMD and OSCC in other areas of the oral cavity has not been previously studied.…”

Section: Discussionmentioning

confidence: 99%

“…nEGFR is expressed in many healthy tissues, where it is involved in the regulation of transcription, cell proliferation, replication, and DNA repair 18,30,31 . However, the particular attention of scientists has been attracted by its overexpression in tumor tissues of the ovary, breast, larynx, oropharyngeal carcinoma, and squamous cell carcinoma of the esophagus, where it has been shown to negatively affect survival 18,22,32–34 . Taguchi found nEGFR expression in 28% of patients with tongue squamous cell carcinoma, but without correlation with clinicopathologic factors 35 .…”

Section: Discussionmentioning

confidence: 99%

Significance of nuclear EGFR and ABCG2 expression in malignant transformation of oral potentially malignant disorders

et al. 2022

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Background The purpose of this study was to investigate the expression of nuclear EGFR (nEGFR) and the stem cell marker ABCG2 in oral leukoplakia (OL) and oral erythroplakia (OE) and to assess their significance as prognostic biomarkers for malignant transformation. Methods In this study we included 50 patients with oral potentially malignant disorders (OPMD), 31 with OL and 19 with OE, in whom we examined the expression of nEGFR and ABCG2 by immunohistochemical methods. Results Twenty‐one (42%) of 50 patients with OL and OE developed oral squamous cell carcinoma (OSCC). The malignant transformation was increased 12,84‐fold (95% CI, 2.15–76.44, p = 0.005) in OPMD expressing both ABCG2 and nEGFR. Expression of nEGFR is a strong indicator of malignant transformation, unlike ABCG2 expression, respectively. Conclusions Determining the co‐expression of the biomarkers nEGFR and ABCG2 in OPMD may serve us to determine the risk of malignant transformation in OSCC.

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Nuclear EGFR Expression Is Associated With Poor Survival in Laryngeal Carcinoma

Abstract: The membrane EGFR (mEGFR) protein over-

Cited by 12 publications

References 33 publications

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma

Significance of nuclear EGFR and ABCG2 expression in malignant transformation of oral potentially malignant disorders

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