Focus on High-Risk DTC Patients

Piccardo, Arnoldo; Arecco, Federico; Puntoni, Matteo; Foppiani, Luca; Cabria, Manlio; Corvisieri, Stefania; Arlandini, Anselmo; Altrinetti, Vania; Bandelloni, Roberto; Orlandi, Fabio

doi:10.1097/rlu.0b013e318266d4d8

Cited by 87 publications

(40 citation statements)

References 17 publications

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“…Preferentially methylated cancer also tended to have larger tumors and higher thyroglobulin levels, which might relate to cancer progression (Piccardo et al, 2013). Although 90% of papillary thyroid cancers are considered to be at low risk with a mortality rate of 1–2%, the mortality rate of the high risk group is 50–75% (Hay et al, 1993; Noguchi et al, 1994; Shaha et al, 1996; Dean and Hay, 2000).…”

Section: Discussionmentioning

confidence: 99%

Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation

et al. 2013

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Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7) was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2′-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P = 0.04, Fisher's exact test). Thus, we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation

et al. 2013

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“…Stimulated Tg assessment was performed after withdrawal TSH from thyroid replacement therapy or after stimulation with recombinant human TSH. Not only is a high stimulated Tg level of >10 µg/mL considered an indicator of recurrent/metastatic disease in patients with DTC, but a high stimulated Tg level of ≥50 µg/mL is associated with shorter PFS and OS in patients with DTC (32). Because a gradual increase in the TgAb titer after thyroidectomy can be used as a predictor of persistent or recurrent disease in patients with DTC with a negative serum Tg level (15,16), we investigated whether high levels of TgAb are also associated with shorter PFS and OS of patients with PTC with lung metastases.…”

Section: Discussionmentioning

confidence: 99%

Lung Metastases From Papillary Thyroid Cancer With Persistently Negative Thyroglobulin and Elevated Thyroglobulin Antibody Levels During Radioactive Iodine Treatment and Follow-Up: Long-Term Outcomes and Prognostic Indicators

et al. 2020

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Background: The lung is the most frequent site of distant metastasis from differentiated thyroid cancer (DTC). However, lung metastasis from papillary thyroid cancer (PTC) with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels is an extremely rare entity, and the prognosis is therefore elusive. We investigated the clinical characteristics, long-term outcomes, and prognostic factors of lung metastases in PTC patients with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels during radioactive iodine (131 I) treatment and follow-up. Methods: We retrospectively reviewed 10,482 patients with DTC who underwent postoperative 131 I treatment from 2007 to 2017 at Shanghai Sixth's People's Hospital. The relationships between progression-free survival (PFS) and several variables were assessed by univariate and multivariate analyses using the Kaplan-Meier method and a Cox proportional hazards model, respectively. Results: Forty-seven patients with PTC were enrolled in this study (4.48‰ of all patients with DTC). The median age at the initial diagnosis of lung metastasis was 39.6 ± 15.4 years, and the patients comprised 14 male and 33 female patients (male: female ratio = 1.00:2.36). Twenty-five patients had 131 I avidity and 22 had non-131 I avidity. At the end of the 5-years follow-up, 12 patients exhibited progressive disease (PD), and 2 patients had died. At the end of the 10-years follow-up, 21 patients showed PD and five patients had died. The 5-and 10-year PFS rates were 74.47 and 53.32%, respectively; the 5-and 10-years overall survival (OS) rates were 95.74 and 89.36%, respectively. The timing of diagnosis of lung metastases, maximal size of lung metastases, and 131 I avidity were significantly associated with the 5-years PFS rate (P = 0.035, P = 0.030, and P<0.001, respectively). Only 131 I avidity was associated with the 10-years PFS rate (P < 0.001). The multivariate analyses also showed that non-131 I avidity were the independent poor prognostic factors for 10-years PFS at the end of follow-up (P < 0.001). Qiu et al. Lung Metastases From PTC With Elevated TgAb Conclusions: Lung metastases from PTC in patients with persistently negative Tg and elevated TgAb levels had an excellent prognosis and survival rate during 131 I treatment and follow-up. The loss of 131 I avidity remained the strongest independent predictor of a poor prognosis and survival in these patients.

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“…Hence, the recommendation for TSH stimulation to achieve optimal Tg measurement sensitivity traditionally interested any patient with DTC who has low-or high-risk stages of disease and received at least one course of ablative radioiodine therapy. (20,21,29). Finally, even if hsTg values <0.1 μg/L are reassuring, slightly detectable values (i.e.…”

Section: Pros: Rhtsh-stimulated Tg Testing During Dtc Follow-upmentioning

confidence: 96%

“…Several studies have suggested that a high serum Tg level measured after thyroidectomy and just before RAI therapy (preablation Tg) could be a prognostic marker for predicting DTC recurrence or metastases (28,29). A meta-analysis of 3947 patients across a broad spectrum of disease demonstrated that the preablation Tg level is a useful negative predictor of persistent and recurrent DTC.…”

Section: Tg Measurement After Surgery/before Rai Therapy (Preablationmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: The role of rhTSH in the management of differentiated thyroid cancer: pros and cons

Giovanella

Duntas

2019

European Journal of Endocrinology

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The use of recombinant human thyrotropin (rhTSH) testing in the diagnosis and therapy of differentiated thyroid cancer (DTC) has been adopted over the last two decades as an alternative to the classical thyroid hormone withdrawal avoiding the threat of hypothyroidism. Serum thyroglobulin (Tg) measurement is crucial for monitoring DTC patients over time. Until about a decade ago, optimal sensitivity of Tg assays for the detection of smaller disease foci required Tg measurement after thyrotropin (TSH) stimulation, carried out following thyroid hormone withdrawal or rhTSH administration. In very recent years, significant improvements in assay technology have resulted in highly sensitive Tg (hsTg) assays, sufficiently sensitive to obviate the need for rhTSH stimulation in most DTC patients. The aim of this paper is to review and discuss, via a 'pros and cons' approach, the current clinical role of rhTSH to stimulate radioiodine (RAI) uptake for treatment and/or imaging purposes and to increase the clinical sensitivity of Tg measurement for monitoring DTC patients when high-sensitive Tg assays are available.

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Focus on High-Risk DTC Patients

Cited by 87 publications

References 17 publications

Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation

Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation

Lung Metastases From Papillary Thyroid Cancer With Persistently Negative Thyroglobulin and Elevated Thyroglobulin Antibody Levels During Radioactive Iodine Treatment and Follow-Up: Long-Term Outcomes and Prognostic Indicators

MANAGEMENT OF ENDOCRINE DISEASE: The role of rhTSH in the management of differentiated thyroid cancer: pros and cons

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