Cyclooxygenase‐2 expression in medullary thyroid carcinoma

Popovtzer, Aron; Morgenstein, Sara; Roizman, Pepi; Gutman, Dan; Bahar, Gideon; Stern, Yoram; Feinmesser, R

doi:10.1002/hed.20542

Cited by 5 publications

(3 citation statements)

References 45 publications

(25 reference statements)

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“…In this study, cox‐2 expression was observed in 50% of MTCs and in only 13% of FTCs. The higher prevalence of cox‐2 expression in MTC is in agreement with reports in humans, where 26–41% of FTCs and 75–82% of MTCs have been shown to express cox‐2 . In a study investigating cox‐2 expression in canine invasive TCC of the urinary bladder, the percentage of positive tumor cells at diagnosis ranged from 1 to 22%, comparable to that found in our study .…”

Section: Discussionsupporting

confidence: 92%

Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Campos

Ducatelle

Kooistra

et al. 2014

Veterinary Internal Medicne

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BackgroundThyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease.Hypothesis/ObjectivesTo investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors.Animals74 dogs with thyroid neoplasia.MethodsImmunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase‐2 (cox‐2), and P‐glycoprotein (P‐gp).ResultsFifty‐four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76–100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox‐2. Seven percent of FTCs and 70% of MTCs expressed P‐gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox‐2 (P = .013), and P‐gp (P < .001) was significantly higher in MTCs compared to FTCs.Conclusions and Clinical Importance VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox‐2 and P‐gp may be useful molecular targets in canine MTC.

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Section: Discussionsupporting

confidence: 92%

Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Campos

Ducatelle

Kooistra

et al. 2014

Veterinary Internal Medicne

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“…COX-2 expression has been explored in neuroendocrine tumours, including studies of the biological potential and therapeutic possibilities. It was widely expressed in up to 82% of medullary thyroid carcinoma, showing statistically significant up-regulation in comparison with benign thyroid tissue [113]. In phaeochromocytoma, COX-2 is associated with malignant behaviour and, along with lack of nm-23 and presence of galectin-3, can be applied to predict malignancy [114].…”

Section: Cox-2mentioning

confidence: 99%

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Simtniece¹,

Vanags²,

Štrumfa³

et al. 2015

pjp

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The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p < 0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p = 0.022), the World Health Organization 2004 and 2010 classification grades (p = 0.021 and p = 0.002), stage (p = 0.028) and mitotic count (p = 0.007) but among molecular markers -with CK19 (p = 0.033) and vimentin (p = 0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p = 0.018), pR (p = 0.025), vascular (p = 0.020), perineural (p = 0.026) and lymphatic invasion (p = 0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.

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“…The expression of COX-2 in MTC was evaluated in an immunohistochemical study by Popovtzer et al [95]. They evaluated tissue specimens of 22 patients with MTC and 15 control subjects with non-malignant thyroid tissue, concluding that COX-2 is overexpressed in the MTC tissue.…”

Section: Molecular Biology Of Mtc and The Ret Proto-oncogenementioning

confidence: 99%

Medullary Thyroid Cancer: Molecular Biology and Novel Molecular Therapies

Çakır¹,

Grossman²

2009

Neuroendocrinology

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Medullary thyroid cancer (MTC) arises from neural-crest-derived parafollicular C cells of the thyroid gland and accounts for approximately 4% of all thyroid cancers. Up to 25–30% of MTC cases occur as inherited disorders while the remaining cases represent the sporadic form of the disease. In this review, the structure and signalling properties of the RET proto-oncogene in its wild-type and mutant forms, and its role in hereditary and sporadic MTC, are discussed. A full data search was performed through PubMed over the years 2000–2008 with the key words ‘medullary thyroid cancer, treatment, molecular biology, RET, molecular mechanism’, and all relevant publications have been included, together with selected publications prior to that date. We also review novel therapies for metastatic MTC, especially the tyrosine kinase inhibitors which have activity at multiple receptor subtypes, and summarize the current ongoing trials in this area. While such tyrosine kinase inhibitors, particularly those affecting RET activity such as vandetanib, sorafenib and sunitinib, are promising, the low rate of partial responses and absence of complete responses in all of the various trials of monotherapy emphasize the need for new and more effective single agents or combinations of therapeutic agents with acceptable toxicity.

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Cyclooxygenase‐2 expression in medullary thyroid carcinoma

Abstract: COX-2 is expressed significantly in MTC including a larger area of staining and greater intensity than in nonmalignant thyroid tissue. These findings may have important treatment implications for the use of COX-2 inhibitors in patients with MTC.

Cited by 5 publications

References 45 publications

Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Medullary Thyroid Cancer: Molecular Biology and Novel Molecular Therapies

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