scholarly journals Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

2015 ◽  
Vol 173 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Guia Vannucchi ◽  
Simone De Leo ◽  
Michela Perrino ◽  
Stefania Rossi ◽  
Delfina Tosi ◽  
...  

BackgroundThyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors.MethodsWe studied the expression of estrogen receptor α (ERα or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features.ResultsERα and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER- and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the ‘receptor conversion’ phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERα-positive primary tumors analyzed had ERα-negative metastatic lymph nodes. At the genetic analyses,BRAFV600Emutation was detected in 23.2% of the tumors and had a higher prevalence in larger tumors and in those with a stronger ERα or PR staining.ConclusionsThe whole of the findings reported in the present study argue for an association between ERα and PR sex hormone receptor expression and a more aggressive presentation. Although no impact on outcome was found, the evaluation of ERα and PR receptor expression could add insights into the biological behavior of tumors and could modify the follow-up, particularly in fertile women affected with persistent disease.

2016 ◽  
Vol 5 (4) ◽  
pp. 224-230 ◽  
Author(s):  
Giacomo Sturniolo ◽  
Carles Zafon ◽  
Mariacarla Moleti ◽  
Josep Castellví ◽  
Francesco Vermiglio ◽  
...  

Cancer ◽  
2010 ◽  
Vol 117 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Menno R. Vriens ◽  
Willieford Moses ◽  
Julie Weng ◽  
Miao Peng ◽  
Ann Griffin ◽  
...  

2020 ◽  
Vol 9 (8) ◽  
pp. 2481
Author(s):  
Kirk Jensen ◽  
Shilpa Thakur ◽  
Aneeta Patel ◽  
Maria Cecilia Mendonca-Torres ◽  
John Costello ◽  
...  

The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.


Author(s):  
Carla Colombo ◽  
Emanuela Minna ◽  
Chiara Gargiuli ◽  
Marina Muzza ◽  
Matteo Dugo ◽  
...  

Abstract Background Papillary thyroid cancer (PTC) is the most frequent endocrine tumor. Radioiodine (RAI) treatment is highly effective in these tumors, but up to 60% of metastatic cases become RAI-refractory. Scanty data are available on either the molecular pattern of radioiodine refractory papillary thyroid cancers (PTC) or the mechanisms responsible for RAI resistance. Methods We analyzed the molecular profile and gene/miRNA expression in primary PTCs, synchronous and RAI-refractory lymph node metastases (LNMs) in correlation to RAI avidity or refractoriness. We classified patients as RAI+/D+ (RAI uptake/disease persistence), RAI−/D+ (absent RAI uptake/disease persistence), and RAI+/D- (RAI uptake/disease remission), and analyzed the molecular and gene/miRNA profiles, and the expression of thyroid differentiation (TD) related genes. Results A different molecular profile according to the RAI class was observed: BRAFV600E cases were more frequent in RAI−/D+ (P = 0.032), and fusion genes in RAI+/D+ cases. RAI+/D- patients were less frequently pTERT mutations positive, and more frequently wild type for the tested mutations/fusions. Expression profiles clearly distinguished PTC from normal thyroid. On the other hand, in refractory cases (RAI+/D+ and RAI−/D+) no distinctive PTC expression patterns were associated with either tissue type, or RAI uptake, but with the driving lesion and BRAF−/RAS-like subtype. Primary tumors and RAI-refractory LNMs with BRAFV600E mutation display transcriptome similarity suggesting that RAI minimally affects the expression profiles of RAI-refractory metastases. Molecular profiles associated with the expression of TPO, SLC26A4 and TD genes, that were found more downregulated in BRAFV600E than in gene fusions tumors. Conclusions The present data indicate a different molecular profile in RAI-avid and RAI-refractory metastatic PTCs. Moreover, BRAFV600E tumors displayed reduced differentiation and intrinsic RAI refractoriness, while PTCs with fusion oncogenes are RAI-avid but persistent, suggesting different oncogene-driven mechanisms leading to RAI refractoriness.


2000 ◽  
Vol 151 (8) ◽  
pp. 765-772 ◽  
Author(s):  
M. A. Rossing ◽  
L. F. Voigt ◽  
K. G. Wicklund ◽  
J. R. Daling

Author(s):  
Dong Chen ◽  
Yawen Tan ◽  
Zhichao Li ◽  
Wujiao Li ◽  
Lei Yu ◽  
...  

Abstract Context Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs. There is a pressing need for clinically relevant preclinical thyroid cancer models for personalized therapy because of the lack of in vitro models that faithfully represent the biology of the parental tumors. Objective To understand thyroid cancer and translate this knowledge to clinical applications, patient-derived PTC organoids as a promising new preclinical model were established. Methods Surgically resected PTC primary tissues were dissociated and processed for organoid derivation. Tumor organoids were subsequently subjected to histological characterization, DNA sequencing, drug screen, and cell proliferation assay, respectively. Results We describe a 3-dimensional culture system for the long-term expansion of patient-derived PTC organoid lines. Notably, PTC organoids preserve the histopathological profiles and genomic heterogeneity of the originating tumors. Drug sensitivity assays of PTC organoids demonstrate patient-specific drug responses, and large correlations with the respective mutational profiles. Estradiol was shown to promote cell proliferation of PTC organoids in the presence of estrogen receptor α (ERα), regardless of the expression of ERβ and G protein–coupled ER. Conclusion These data suggest that these newly developed PTC-derived organoids may be an excellent preclinical model for studying clinical response to anticancer drugs in a personalized way, as well as provide a potential strategy to develop prevention and treatment options for thyroid cancer with ERα-specific antagonists.


2013 ◽  
Vol 5 (3) ◽  
pp. 797-800 ◽  
Author(s):  
GUO-AN ZHANG ◽  
SEN HOU ◽  
SHA HAN ◽  
JIAN ZHOU ◽  
XU WANG ◽  
...  

2020 ◽  
Author(s):  
Xiwu Ouyang ◽  
Lemeng Feng ◽  
Lei Yao ◽  
Yao Xiao ◽  
Gewen Zhang ◽  
...  

Abstract Background: The incidence and mortality of papillary thyroid cancer (PTC) have steadily increased. Although conventional therapies are very effective towards differentiated PTC patients, very limited therapeutic options are applicable to those patients with distant metastases. Therefore, better understanding of the molecular biology of metastatic PTC helps identify novel targets and facilitates the development of new therapies.Methods: Western blot assay was used to check relative gene protein expression. Transwell invasion assay was used to check the invasion capacity of the PTC cells. Wound healing assay was conducted to check the migration capacity of the PTC cells. qRT-PCR assay was used to check relative RNA expression of the cells. IHC assay was used to check TR4 and MMP9 expression in clinical samples or mouse tumor samples. Results: In this study, we first found that testicular orphan receptor 4 (TR4) was significantly increased in PTC tumors spreading to lymph node compared to the paired primary tumors. Experimental evidence suggested that TR4 drove PTC progression via promoting its cell invasion and cell migration. Mechanistically, TR4 transcriptionally regulated the expression level of circ-FLNA, which competed with MMP9 for miR-149-5p binding and led to increased protein level of MMP9. Interruption assays with various gene manipulations verified that TR4/circ-FLNA/miR-149-5p/MMP9 signaling axis played central role in cell invasion and cell migration of PTC cells. Moreover, xenografted mouse model also confirmed that TR4/circ-FLNA signal promoted PTC tumor growth.Conclusions: Overall, our study pinpoints the oncogenic role of TR4 in PTC development and targeting TR4/circ-FLNA/miR-149-5p/MMP9 signaling may be an alternative option for metastatic PTC patients.


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