In the original publication [...].

Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated β-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men.

The American Cancer Society predicted more than 52 000 new cases of thyroid cancer in 2020, making it the most prevalent endocrine malignancy. Due to the approximately threefold higher incidence of thyroid cancer in women, we hypothesize that androgens and/or androgen receptors play a protective role and that thyroid cancer in men represents an escape from androgen-mediated cell regulation. The analysis of androgen receptor (AR) expression in patient tissue samples identified a 2.7-fold reduction in AR expression (p < 0.005) in papillary thyroid cancer compared with matched, normal tissue. An in vitro cell model was developed by stably transfecting AR into 8505C undifferentiated thyroid cancer cells (resulting in clone 84E7). The addition of DHT to the clone 84E7 resulted in AR translocation into the nucleus and a 70% reduction in proliferation, with a shift in the cell cycle toward G1 arrest. RNASeq analysis revealed significant changes in mRNA levels associated with proliferation, cell cycle, and cell cycle regulation. Furthermore, androgen significantly decreased the levels of the G1-associated cell cycle progression proteins cdc25a CDK6 CDK4 and CDK2 as well as increased the levels of the cell cycle inhibitors, p27 and p21. The data strongly suggest that DHT induces a G1 arrest in androgen-responsive thyroid cancer cells. Together, these data support our hypothesis that AR/androgen may play a protective, antiproliferative role and are consistent with younger men having a lower incidence of thyroid cancer than women.

Thyroid cancer is the most prevalent endocrine malignancy in the United States with greater than 53,000 new cases in 2020. There is a significant gender disparity in disease incidence as well, with women developing thyroid cancer three times more often than men; however, the underlying cause of this disparity is poorly understood. Using RNA-sequencing, we profiled the immune landscape of papillary thyroid cancer (PTC) and identified a significant inverse correlation between androgen receptor (AR) levels and the immune checkpoint molecule PD-L1. The expression of PD-L1 was then measured in an androgen responsive-thyroid cancer cell line. Dihydrotestosterone (DHT) treatment resulted in significant reduction in surface PD-L1 expression in a time and dose-dependent manner. To determine if androgen-mediated PD-L1 downregulation was AR-dependent, we treated cells with flutamide, a selective AR antagonist, and prior to DHT treatment to pharmacologically inhibit AR-induced signaling. This resulted in a > 90% restoration of cell surface PD-L1 expression, suggesting a potential role for AR activity in PD-L1 regulation. Investigation into the AR binding sites showed AR activation impacts NF-kB signaling by increasing IkBα and by possibly preventing NF-kB translocation into the nucleus, reducing PD-L1 promoter activation. This study provides evidence of sex-hormone mediated regulation of immune checkpoint molecules in vitro with potential ramification for immunotherapies.

Thyroid cancer is among the most common endocrine malignancies, with papillary thyroid cancer (PTC) accounting for approximately 80% of new thyroid cancer cases in 2017 (ACS). Despite the high sensitivity (95%) of ultrasound-guided fine needle aspiration biopsies (FNAB), approximately 20% of FNA biopsies are indeterminate, which require resection, despite the fact that about 50% are benign. The outcome is that many patients undergo surgical resection of benign disease resulting in avoidable iatrogenic morbidity, and about $700 million in health care costs. Thus, identifying diagnostic/prognostic molecular signatures of PTC would greatly reduce the number of costly, unnecessary resections following indeterminate biopsies. Following consenting of NYEEI patients, surgery, and diagnosis by the pathologist, RNA was prepared from PTC and matched-normal tissue samples, rRNA eliminated and RNA-Seq performed (100bp, paired-end). STARv2.5.2b/ htseq-countv0.6.1 and DESeq2 were used to align raw sequences, and measure transcript abundance. Preliminary bioinformatics analysis was performed with Advaita's iPathway Software. Over 1500 protein-coding transcripts, and 386 lincRNAs achieved 1.5 fold level differential expression (p= 0.05). Gene Ontology enrichment analysis indicated that locomotion, cell motility, signaling, cell differentiation and cell communication were among the most statistically significantly biological processes altered between PTC and matched-normal tissue. Cytokine, signal transducer, ion channel activity, receptor and growth factor activities were among the most statistically significantly molecular functions altered between PTC and matched, normal tissue. Additionally, Pathway Analysis indicated that cell adhesion molecules, cytokine-cytokine receptor, ECM-receptor, cancer, proteoglycans and Jak-Stat signaling were significantly altered. Thyroid differentiation scores (TDS) were calculated for each patients and correlations between differentially expressed lincRNA’s and the TDS were identified. We expect followup experiments modulating the expression of lincRNAs most strongly correlated to the TDS will augment the expression of iodine-handling genes and differentiation in PTC cell lines. We anticipate that the detailed bioinformatics analysis of our coding and noncoding databases in addition to evidence from in vitro studies will yield new diagnostic/prognostic biomarkers, and therapeutic targets. Citation Format: Sina Dadafarin, Anvita Gupta, Katharine Dermigny, Leyla Cavdar, Brandon Pecchia, Melanie Jones, Timmy O'Connell, JK Rasamny, Nina Suslina, Codrin Iacob, Monica Schwarcz, Ameet Kamat, Cameron Budenz, Craig Berzofsky, Deya Jourdy, Tali Lando, Stimson Schantz, Sarnath Singh, Edward Shin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Investigating coding and non-coding RNA in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3570.

Abstract Thyroid cancer (ThCa) is the most rapidly increasing cancer in the US with 56,870 new cases expected in 2017. Interestingly, there is a disparity in incidence between females and males, with women developing ThCa three times more often than men. Immune elimination of nascent tumor cells may explain the difference in disease incidence between sexes. To address this hypothesis, the effect of androgen on immune checkpoint molecule expression in an androgen responsive-thyroid cancer cell line was examined. The undifferentiated ThCa cell line, 8505C, was transfected with androgen receptor (AR) yielding 84E7, a clone that constitutively expresses AR. RNASeq was performed on 8505C and 84E7, treated without and with the AR ligand, 5α-dihydrotestosterone (DHT). PD-L1 was the sole immune checkpoint molecule that exhibited a significant expression change with a 72% reduction in mRNA content. Additional studies provided evidence of qualitative (immunofluorescence) and quantitative (flow cytometry, western blotting) DHT-mediated decreases in PD-L1 expression, with the PD-L1 decreases being both time- and dose-dependent. To further confirm that the effect was specific to AR and PD-L1, we pre-treated 84E7 with flutamide, a selective AR antagonist, to pharmacologically inhibit DHT-mediated AR signaling. This resulted in a dose-dependent and >90% restoration of cell surface PD-L1 expression, evidencing a definitive link between AR activation and PD-L1 signaling. Preliminary investigation into the mechanistic link between AR and PD-L1 shows that NFkB signaling is the likely intermediary. AR activation increases IkBα expression thereby preventing NFkB translocation into the nucleus, resulting in decreased PD-L1 transcription. Furthermore, in human tissue samples from TCGA (n=55), we found female thyroid tissue is significantly enriched with PD-L1 as compared to male thyroid tissue (p=0.0073). Finally, an inverse relationship exists in which AR expression is decreased and PD-L1 expression is increased in human thyroid tumor tissue samples as compared to normal thyroid tissue samples in both TCGA (n=55, p<0.005) and NYMC (n=56, p<0.005) RNAseq datasets. These results are significant in that PD-L1 is expressed by tumor cells as a strategy for evading the immune response allowing for continued tumor growth and metastases. In the thyroid, the presence of androgen-activated AR could lead to an environment that is more favorable for immune system activation and may help eliminate nascent ThCa cells. Thus, men experience a decreased incidence of ThCa due to an immunologically enhanced anti-tumor microenvironment. Alternatively, higher expression levels of PD-L1 observed in female thyroid cancer patients help explain the increased incidence of ThCa and may indicate an opportunity for sex-based therapeutics. Citation Format: Timmy J. O'Connell, Anvita Gupta, Melanie Jones, Tali Lando, Deya Jourdy, Edward Shin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Does androgen attenuation of PD-L1 expression in thyroid cancer modulate disease incidence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2737.

Giant cell angiofibroma (GCA) was first described in 1995, as a previously unrecognized soft tissue tumor of the orbit. Since that time, rare extraorbital head and neck manifestations of GCA have been documented. To the best of our knowledge, we present the fourth documented case of GCA of the buccal cavity, constituting the largest dominant site of occurrence in the extraorbital head and neck.

Abstract Background: The American Cancer Society (ACS) estimated 56,870 new cases of thyroid cancer in the United States in 2017, with roughly 2,010 deaths attributed to the disease. The incidence of thyroid cancer has been increasing steadily over the past three decades, with Papillary Thyroid Cancer (PTC) being the most prevalent form of this endocrine malignancy, comprising of about 90% of all cases. Appreciably, Surveillance, Epidemiology, and End Results (SEER) and the ACS indicate that the incidence of PTC in the age group of 20-49 years is three to four times more prevalent in women than in men. This epidemiologic finding suggests that the female thyroid is at a higher risk of developing PTC. Methods: The Cancer Genome Atlas (TCGA) database provides the means to address the differences between male and female thyroids on the molecular level. Using the normalized Level 3 RNA Seq Data and patient pathology reports available on the TCGA Data Portal, differential gene expression of 56 non-neoplastic/normal thyroid samples (40 women; 16 men) was investigated using the biological analysis software, Subio platform, version v1.20.5031. (Subio Inc., Tokyo, Japan). Results: Immune/inflammatory genes exhibited a higher expression in uninflamed, normal thyroid tissue of women than in men (>1.5 fold; p<0.05). The expression levels of these genes were increased in male PTC samples, compared to their matched normal tissue. The level of expression of immune/inflammatory genes in women approximated their expression levels in matched PTC tissue of women and men, indicating that normal thyroid tissue in women exhibits a neoplastic level of inflammation. Conclusions: Our data suggest that the female thyroid may be “at-risk” for developing PTC due to underlying and on-going immune/inflammatory processes. Citation Format: Anvita Gupta, Karnika Singh, Timmy J. O'Connell, Melanie Jones, JK Rasamny, Monica Schwarcz, Augustine Moscatello, Edward Shin, Raj Tiwari, Jan Geliebter. Underlying inflammatory processes in non-neoplastic female thyroid serve as an immunological basis for the sex disparity in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5750.

Abstract Thyroid cancer is among the most common endocrine malignancies, with papillary thyroid cancer (PTC) accounting for approximately 80% of new thyroid cancer cases in 2017 (ACS). Despite the high sensitivity (95%) of ultrasound-guided fine needle aspiration biopsies (FNAB), approximately 20% of FNA biopsies are indeterminate, which require resection, despite the fact that about 50% are benign. The outcome is that many patients undergo surgical resection of benign disease resulting in avoidable iatrogenic morbidity, and about $700 million in health care costs. Thus, identifying diagnostic/prognostic molecular signatures of PTC would greatly reduce the number of costly, unnecessary resections following indeterminate biopsies. Following consenting of NYEEI patients, surgery, and diagnosis by the pathologist, RNA was prepared from PTC and matched-normal tissue samples, rRNA eliminated and RNA-Seq performed (100bp, paired-end). STARv2.5.2b/ htseq-countv0.6.1 and DESeq2 were used to align raw sequences, and measure transcript abundance. Preliminary bioinformatics analysis was performed with Advaita's iPathway Software. Over 1500 protein-coding transcripts, and 386 lincRNAs achieved 1.5 fold level differential expression (p= 0.05). Gene Ontology enrichment analysis indicated that locomotion, cell motility, signaling, cell differentiation and cell communication were among the most statistically significantly biological processes altered between PTC and matched-normal tissue. Cytokine, signal transducer, ion channel activity, receptor and growth factor activities were among the most statistically significantly molecular functions altered between PTC and matched, normal tissue. Additionally, Pathway Analysis indicated that cell adhesion molecules, cytokine-cytokine receptor, ECM-receptor, cancer, proteoglycans and Jak-Stat signaling were significantly altered. Linc01614, linc00475, linc01510, RP11-244M2.1, linc00511, linc01314 and linc00973 were the most overexpressed lncRNAs. Patients who had lymph node metastasis showed differential expression compare to patients with localized disease. These same patients had statistically significantly alterations in the negative regulation of adhesion-dependent cell spreading and cell-matrix adhesion, establishment of cell polarity, and protein kinase C signaling according to Gene Ontology enrichment analysis. In addition to capturing protein coding transcripts, our RNA processing technique has enriched our RNASeq database for novel, noncoding RNAs that are known to play critical roles in cell homeostasis. The biological significance of differentially expressed RNA transcripts is currently being investigated. We anticipate that the detailed bioinformatics analysis of our coding and noncoding databases will yield new diagnostic/prognostic biomarkers, and therapeutic targets. Citation Format: Sina Dadafarin, Anvita Gupta, Katharine Dermigny, Melanie Jones, Timmy O'Connell, JK Rasamny, Nina Suslina, Iacob Iacob, Monica Schwarcz,, Ameet Kamat, Cameron Budenz, Craig Berzofsky, Deya Jourdy, Tali Lando, Stimson Schantz, Sarnath Singh, Edward Shin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Coding and non-coding RNA in papillary thyroid cancer - markers for disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2469.

The objective of this report is to summarize the symptoms, diagnostic workup, necessary imaging, and management of Eagle syndrome. A comprehensive literature review was conducted on peer-reviewed publications of Eagle syndrome across multiple disciplines in order to gain a thorough understanding of the presentation, diagnosis, and management of this disorder. Diagnoses of Eagle Syndrome have increased, in part due to the awareness of physicians to patient symptomatology. While cervical pain and dysphagia are among the typical symptoms, patients can present with a wide spectrum of benign and dangerous symptoms. CT scan is the gold standard for diagnosis and can be aided by both 3D reconstructive imaging and Angiography. Treatment strategies include medical management (analgesics, corticosteroids, antidepressants, and anticonvulsants) and varied surgical approaches (extraoral, transoral, endoscopic assisted). Increased understanding by providers treating patients with Eagle Syndrome allows for a more comprehensive treatment plan. With a variety of medical regimens and more definitive surgical approaches, Eagle Syndrome can be treated safely and effectively.

Abstract Thyroid cancer is the most rapidly increasing cancer in the US with 64,300 new cases expected in 2016. However, there is a disparity in the incidence of thyroid cancer between females and males, with women (49,350 expected cases) developing thyroid cancer three times more often than men (14,950 expected cases). Immune elimination of nascent tumor cells may explain the difference in disease incidence between men and women. To address this hypothesis, the effect of androgen on the expression of immune checkpoint molecules in an androgen responsive-thyroid cancer cell line was examined. The undifferentiated thyroid cancer cell line, 8505C, does not express a functional androgen receptor (AR). 84E7 is a clone of 8505C that was transfected with an AR containing plasmid resulting in constitutively expressed AR. Transcriptome analysis via RNASeq was performed on 8505C and 84E7, with and without 5α-dihydrotestosterone (DHT) treatment. Raw sequencing reads were aligned to the UCSC hg19 human reference genome with Tophat, and Cufflinks was used to measure transcript abundances in Reads Per Kilobase of exon model per Million mapped reads (RPKM) as well as to find genes with statistically significant changes in expression. DHT treatment of 84E7 resulted in >2 fold expression changes in 1,552 genes. We examined the immune checkpoint ligands expressed on 84E7 such as CD80, CD86, PD-L1, PD-L2, ICOSL, B7-H3, B7-H4, HVEM, 4-1BBL, OX40L, CD70, CD40, and GAL9. PD-L1 was the sole immune checkpoint molecule that exhibited a significant expression change in DHT-treated 84E7 cells with a 1.8 log2 fold decrease (p=0, q=0), or 72% reduction in mRNA content. Additional studies confirmed the RNASeq results and provide evidence of both qualitative (immunofluorescence) and quantitative (flow cytometry and western blotting) decreases in PD-L1 expression with DHT treatment. These results are significant in that PD-L1 is produced by tumor cells as a strategy for subverting and evading the immune response, specifically T cells, allowing for continued tumor growth and metastases. In the thyroid, the presence of activated androgen receptors could lead to an environment that is more favorable for immune system activation and may help eliminate nascent thyroid cancer cells. Thus, men may experience a decreased incidence of thyroid cancer due to an enhanced and less inhibited anti-tumor environment. Citation Format: Timmy J. O'Connell, Melanie Jones, Anvita Gupta, Tali Lando, Deya Jourdy, Edward Shin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Androgen receptor stimulation with 5α-dihydrotestosterone (DHT) decreases PD-L1 expression in androgen-responsive thyroid cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5575. doi:10.1158/1538-7445.AM2017-5575

Abstract Papillary Thyroid Cancer (PTC) accounts for the vast majority of thyroid cancers and comprises more than 90% of neoplasms in the endocrine system. In the last 30 years, the incidence and prevalence of PTC has dramatically risen in developed countries, with a three-fold higher incidence in women than in men. With an overall five-year survival rate of 98.1%, early stage PTC has a favorable prognosis. However, PTC exhibits increased aggressiveness with poor prognosis in men diagnosed with the disease. These striking observations led us to explore the role of androgen and androgen receptor (AR) in this disease. We found an approximately 70% decrease in median AR RNA expression (p<0.0001) in 24 PTC patient tissue samples (from New York Eye and Ear Infirmary), compared to matched, normal thyroid tissue. A similar trend was also observed in about 500 PTC samples in the TCGA database, compared with 60 normal thyroid samples. Methylation was explored as a cause for the down-regulation of the AR mRNA in disease pathogenesis, using in-silico methods such as Wanderer, a Maplab tool for TCGA RNA data visualization, and MethylPlotter. A methylation pattern of the AR gene, spanning 7 exons, was generated with 30 methylation sites and, AR in PTC was found to be predominantly methylated at ten sites, compared to matched normal thyroid tissue samples, in the TCGA. Patients with ten or more hypermethylated sites on the AR gene in tumor tissue exhibited a significant decrease in the AR RNA expression in the tumor, versus matched normal thyroid tissue. Methylation of AR (10 or more sites) was accompanied by a nine-fold reduction in AR expression in male PTC, and a five-fold decrease in female PTC. This reduction was not observed in hyper- or equally-methylated normal thyroid tissue. We selected eleven methylation sites in the CpG islands that we predict are essential for AR silencing, with four sites in the AR promoter region. Additionally, we found AR gene-specific and global transcription activators to be downregulated, and repressors up-regulated in the PTC samples. The data adds importance to our previous studies showing induction of senescence in AR-transfected PTC cells in culture, when AR is stimulated with 5α-dihydrotestosterone. In conclusion, our study demonstrates a fine regulation and differential expression of AR associated with methylation, and highlights the significance of epigenetic modifications in thyroid cancer progression. Citation Format: Anvita Gupta, Timmy O'Connell, Melanie Jones, Karnika Singh, Monica Schwarcz, JK Rasamny, Dorota Halicka, Jiangwei Li, Codrin Iacob, Nina Suslina, Stimson Schantz, Edward Shin, Zbigniew Darzynkiewicz, Raj Tiwari, Jan Geliebter. Methylation and expression of androgen receptor in Papillary Thyroid Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4356. doi:10.1158/1538-7445.AM2017-4356

Objectives/HypothesisThe goal of the study was to identify geographic trends in the primary treatment of early-stage glottic cancer.Study DesignRetrospective analysis of the United States National Cancer Institute's Surveillance, Epidemiology, and End-Results (SEER) database.MethodsUsing the most up-to-date November 2014 submission of the SEER database in addition to SEER-18 data files, a cohort was created of stage I to II squamous cell glottic cancer from 2004 to 2012. The treatment groups (radiation and surgery) were compared with respect to several pretreatment covariates including age, race, gender, state where they received treatment, year of diagnosis, and American Joint Committee on Cancer (AJCC) stage.ResultsIn analyzing geographic trends, a statistically significant difference in treatment received by region and state was found (P < .0001.). When examining patient demographics, there was no statistically significant difference in treatment by age (P = .5206), AJCC stage (P = .4922), or year of diagnosis (P = .6593). There was a significant difference in racial distribution by treatment (P = .0038), with patients receiving surgery more likely to be black than patients receiving radiation (12% vs. 10%). In analyzing overall survival (OS), there was no significant difference in OS among the four US treatment regions (P = .2508).ConclusionsGeographic factors impact overall treatment of early-stage glottic cancer. In addition, it was determined that race was a factor that correlated to differences in treatment modality. Finally, overall survival across the United States was determined to be significantly better in patients receiving radiation therapy.Level of Evidence4 Laryngoscope, 126:880-884, 2016

The development of intensity-modulated radiotherapy (IMRT) has played a major role in improving outcomes and decreasing morbidity in patients with head and neck cancer. This review addresses this vital modality with a focus on the important role of the head and neck surgeon. The technique as well as its benefits and points of caution are outlined, the definitions of tumor and treatment volumes are discussed, and the dose and fractionation are detailed. Following this are several sections dedicated to the role of the head and neck surgeon in the planning of both definitive and postoperative radiotherapy to the primary site and neck. There is a focus throughout on anatomic and surgical considerations; commonly encountered situations are illustrated. With a deeper understanding of this technique and their own pivotal contribution to target delineation, head and neck surgeons will be poised to expand their role and improve cancer care for their patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2368-E2373, 2016.

Abstract The American Cancer Society predicts 62,980 new cases of thyroid cancer and 1,890 deaths due to the disease in 2014, making thyroid cancer the most prevalent endocrine malignancy. This is particularly concerning for women who have an approximately three-fold higher incidence of thyroid cancer than men. Significant research has been done to elucidate the role of estrogen as a driver of thyroid cancer. Taking the reverse approach, that men have a much lower incidence of thyroid cancer, led us to hypothesize that androgens and/or androgen receptors play a protective role and that PTC represents the escape from androgen-mediated cell regulation. Analysis of AR expression in 24 PTC patient tissue samples indicated a 2.7 fold reduction in AR expression compared to matched normal tissue (P<0.005). This suggests that the reduction of AR levels in the neoplastic process of thyroid tissue may be one mechanism of escape from androgen regulation. To more fully understand the function of androgen/AR in thyroid cells, the AR was stably transfected into 8505C anaplastic/PTC cells. Addition of DHT to the 8505C-transfected clone, 84E7, resulted in AR translocation into the nucleus and a 70% reduction in proliferation, as well as a shift in the cell cycle toward G1 arrest. Transcription profiling using RNA-Seq and gene ontology analysis revealed significant changes in genes associated with proliferation, cell cycle, and cell cycle regulation confirming the proliferation assay and cell cycle analysis above. Further, when we examined G1 associated cell cycle proteins, we found significant decreases in cell cycle progression proteins cdc25a, CDK6, CDK4, and CDK2 as well as significant increases in the inhibitors p27 and p21. Thus, protein, RNA and cell cycle analysis data are concordant and demonstrate an accumulation of cells in G1 when treated with DHT. Together these data demonstrate that expression of androgen/AR in normal thyroid cells may play a protective, anti-proliferative role that is lost in PTC resulting in dysregulation of genes normally under AR control. The differential expression of androgen/AR in males verses females may provide new insight into the different clinical presentations and outcomes between women and men. Citation Format: Melanie Elizabeth Jones, Timmy O'Connell, Anvita Gupta, Hong Zhao, Codrin Iacob, Augustine Moscatello, Edward Shin, Zbigniew Darzynkiewicz, Raj K. Tiwari, Jan Geliebter. Androgen receptor activation inhibits papillary thyroid carcinoma cell cycle progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 708. doi:10.1158/1538-7445.AM2015-708