Does the Epidermal Growth Factor Receptor Play a Role in the Progression of Thyroid Cancer?

Knauf, Jeffrey A.

doi:10.1089/thy.2011.2111.ed

Cited by 20 publications

(16 citation statements)

References 38 publications

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“…However, these studies always compared one FPA type with the general population, and not among the different categories of FPA. The similar frequency of PTC seen among the different FPA groups in our study may reflect their com- mon etiopathogenic mechanisms, including shared cytokines or growth factors (32)(33)(34). Another possibility is that the genetic and epigenetic factors that cause pituitary adenoma development may also be responsible for PTC.…”

Section: Discussionsupporting

confidence: 58%

Nodular Thyroid Disease and Papillary Thyroid Carcinoma in Functional Pituitary Adenomas

Dogansen¹,

Yalin²,

Tanrikulu³

et al. 2018

Turk J Endocrinol Metab

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Objective: Increased frequency of nodular thyroid disease has been reported in acromegalic patients. Recent studies have also demonstrated an increased coexistence of nodular thyroid disease with Cushing's disease and prolactinoma. In this study, we evaluated the frequency and outcomes of nodular thyroid disease in each type of functional pituitary adenoma. Material and Methods: A total of 232 patients diagnosed with acromegaly (n=138), prolactinoma (n=59) or Cushing's disease (n=35) were included in this retrospective observational study. The frequency of nodular thyroid disease, fine-needle aspiration results, and the frequency of papillary thyroid carcinoma were compared in each group. Factors related to nodule development were evaluated in functional pituitary adenoma patients with or without nodules. Results: Nodular thyroid disease frequency was higher in patients with acromegaly (69%) compared to those with prolactinoma (36%) or Cushing's disease (34%) (p<0.001). Fine-needle aspiration results and PTC frequencies were similar between the groups. In comparison to patients without nodules (n=104), those with nodules (n=128) were older (p=0.01) and had a higher incidence of glucose metabolism disorders (p=0.006). Insulin-like growth factor-1 levels were higher in acromegalic patients with nodular thyroid disease (p=0.01). There was no relationship between nodule formation and baseline prolactin or cortisol/adrenocorticotropic hormone levels in the patients with prolactinomas and Cushing's disease, respectively. Conclusion: Although nodular thyroid disease was more common in acromegalic patients, its incidence in patients with prolactinoma and Cushing's disease were higher than previously reported in our country (23.5%). The most important factors affecting nodule formation in functional pituitary adenoma patients were glucose metabolism disorders and age. Although a higher frequency of PTC has been reported in acromegalic patients, it was similar for all functional pituitary adenoma patients in our study.

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Section: Discussionsupporting

confidence: 58%

Nodular Thyroid Disease and Papillary Thyroid Carcinoma in Functional Pituitary Adenomas

Dogansen¹,

Yalin²,

Tanrikulu³

et al. 2018

Turk J Endocrinol Metab

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“…The most common are deletions in exon 19 (del 2235-2249/2236-2250; del E746-A750), followed by a point mutation in exon 21 (T>G 2573) which results in substitution of leucine by arginine at codon 858 (L858R) (12). Similar somatic mutations have been described in thyroid cancers (13), but these mutations are not well characterized (14) and some studies fail to identify them at all (10, 15). …”

Section: Introductionmentioning

confidence: 60%

“…Though recent evidence implicates EGFR-H in advanced thyroid carcinoma progression (5), the clinicopathologic significance of EGFR or BRAF(V600E) mutations in thyroid carcinomas with EGFR-H is poorly understood. A better understanding of the molecular mutational status in addition to IHC expression is required for effective therapeutic modalities targeting EGFR (14). …”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma

Fisher¹,

Jani²,

Fisher³

et al. 2013

Journal of Surgical Research

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Background Epidermal growth factor receptor (EGFR) overexpression (EGFR-H) is implicated in thyroid carcinoma disease progression, but the clinicopathologic significance of EGFR-H in tumors that harbor EGFR and/or BRAF(V600E) mutations is unknown. Methods Tissue microarrays from 81 patients who underwent thyroidectomies for carcinoma from 2002-2011 were scored for EGFR expression using immunohistochemistry (IHC). Somatic mutations in EGFR exons 19 and 21 and BRAF were analyzed. Correlations between EGFR IHC, EGFR, and BRAF(V600E) mutations and clinicopathologic features were assessed. Results EGFR-H was detected in 39.5% of carcinomas (n=32) from patients with papillary (PTC, 46.2%, n=18), follicular (29.6%, n=8), and anaplastic (ATC, 100.0%, n=6), but not medullary (0.0%, n=9) thyroid carcinoma. BRAF(V600E) mutations were identified in 22.2% of carcinomas (n=18, 15 PTCs and 3 ATCs). No somatic EGFR mutations were detected in any subtype. On PTC univariate analysis, EGFR-H correlated with increasing stage, extrathyroidal extension (ETE), tumor capsule invasion (TCI), adverse pathologic features (APF: any demonstration of ETE, TCI, lymph-vascular invasion, lymph node metastases, and/or distant metastases), and BRAF(V600E) mutations. On multivariate analysis, EGFR-H correlated with BRAF(V600E) mutations. In BRAF wild-type (BRAF-WT) PTCs, the correlation between EGFR-H and APF approached statistical significance (p=0.065). Conclusions EGFR-H may be an important biomarker for aggressive PTCs, particularly in BRAF-WT PTCs. Despite EGFR-H in PTC, FTC, and ATC by immunohistochemistry, somatic EGFR mutations are absent. Therefore, future investigations of EGFR should consider histologic and immunohistochemical methods in addition to molecular profiling of thyroid carcinomas. This multimodality approach is particularly important for future clinical trials testing anti-EGFR therapy.

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“…Amplifications, mutations, or misregulations of EGFR (or one of the other family members) are implicated in approximately 30% of all epithelial cancers. In anaplastic thyroid cancer (ATC), EGFR is overexpressed and implicated in invasion and tumor progression in thyroid cancer [28-30]. …”

Section: Molecular Pathways Involved In Thyroid Cancermentioning

confidence: 99%

Personalization of Targeted Therapy in Advanced Thyroid Cancer

Fallahi

Ferrari

Mazzi

et al. 2014

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Although generally the prognosis of differentiated thyroid carcinoma (DTC) is good, approximately 5% of people are likely to develop metastases which fail to respond to radioactive iodine, and other traditional therapies, exhibiting a more aggressive behavior. Nowadays, therapy is chosen and implemented on a watch-and-wait basis for most DTC patients. Which regimen is likely to work best is decided on the basis of an individual’s clinical information, but only data referring to outcomes of groups of patients are employed. To predict the best course of therapy, an individual patient’s biologic data is rarely employed in a systematic way. Anyway, the use of not expensive individual genomic analysis could lead us to a new era of patient-specific and personalized care. Recently, key targets that are now being evaluated in the clinical setting have been evidenced in the pathogenesis of these diseases. Some of the known genetic alterations playing a crucial role in the development of thyroid cancer include B-Raf gene mutations, rearranged during transfection/ papillary thyroid carcinoma gene rearrangements, and vascular endothelial growth factor receptor-2 angiogenesis pathways. The development of targeted novel compounds able to induce clinical responses and stabilization of disease has overcome the lack of effective therapies for DTC, which are resistant to radioiodine and thyroid stimulating hormone-suppressive therapy. Interestingly, the best responses have been demonstrated in patients treated with anti-angiogenic inhibitors such as vandetanib and XL184 in medullary thyroid cancer, and sorafenib in papillary and follicular DTC.

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Does the Epidermal Growth Factor Receptor Play a Role in the Progression of Thyroid Cancer?

Cited by 20 publications

References 38 publications

Nodular Thyroid Disease and Papillary Thyroid Carcinoma in Functional Pituitary Adenomas

Nodular Thyroid Disease and Papillary Thyroid Carcinoma in Functional Pituitary Adenomas

Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma

Personalization of Targeted Therapy in Advanced Thyroid Cancer

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