Radioactive iodine ablation does not prevent recurrences in patients with papillary thyroid microcarcinoma

Kim, Hye Jeong; Kim, Na Kyung; Choi, Ji Hun; Kim, Se Won; Jin, Sang‐Man; Suh, Sunghwan; Bae, Ji Cheol; Min, Yong‐Ki; Chung, Jae Hoon; Kim, Sun Wook

doi:10.1111/cen.12034

Cited by 72 publications

(54 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RIA may be effective in eradicating cancer cells in metastatic lymph nodes, due to their characteristics regarding iodine uptake (42). However, the indication and efficacy of RIA in low-risk PTMC cases remains questionable (4,43). We still need to determine how indolent PTMC cells respond to stimulation inducing cell proliferation, by TSH or other factors that induce EMT, prior to the application of RIA in low-risk patients.…”

Section: Discussionmentioning

confidence: 99%

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

Nakamura

Onoda

Noda

et al. 2013

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Although papillary thyroid microcarcinoma (PTMC) has an excellent prognosis, certain cases exhibit aggressive clinical manifestations. In this study, we assessed the expression of E-cadherin and Ki-67 in primary PTMC tumors and metastatic lymph nodes, in order to investigate the mechanism underlying the mainly indolent but potentially malignant nature of PTMC. A total of 93 PTMC patients treated in our institute were included in this study. All primary tumors and 57 metastatic lymph nodes were immunohistochemically stained and a total of 73 tumors (78.5%) were positive for E-cadherin. E-cadherin expression was significantly less common at the invasive front (58.1%, P<0.01) compared to that at the center of the tumor. Tumors that had lost E-cadherin expression at the invasive front frequently presented with lymph node metastasis (70.6%). Small tumors (≤5 mm diameter) expressed E-cadherin significantly more frequently compared with larger tumors (P=0.04); however, no other particular characteristic was found to correlate with the status of E-cadherin expression in the primary tumors. E-cadherin expression was detected in 49 (86.0%) of the 57 metastatic foci and correlated significantly with the expression status at the invasive front of the tumor (P=0.02). The Ki-67 index was universally low and was not correlated with the clinicopathological characteristics or the E-cadherin expression of the tumors. These results suggested that cancer cells in the metastatic lymph nodes exhibit indolent characteristics, similar to those of the primary PTMC. However, the metastatic cancer cells may have already completed the process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET), suggesting an innate malignant potential. IntroductionAccording to the World Health Organization classification system for thyroid tumors, papillary thyroid microcarcinoma (PTMC) is defined as a papillary thyroid carcinoma (PTC) measuring ≤10 mm in its greatest dimension (1). The occurrence of PTMC is on the increase worldwide (2-4), along with the frequent application of neck ultrasonography (US) (5,6). PTMC is generally characterized by an indolent clinical course and has an excellent prognosis, with a disease-specific mortality of <0.5% (6). However, certain PTMC cases were found to be clinically aggressive (6,7). According to the observations of Sugitani et al (7), PTMC patients with bulky lymph node metastases or extrathyroidal invasion were at the highest risk for a cancer-specific fatal outcome. Those observations suggested that there is a group of PTMCs that have already acquired highly malignant potential. However, the basic mechanism underlying the development of aggressive characteristics in these tumors has not yet been identified.The reported risk factors for PTMC recurrence were shown to be male gender (8,9), extent of primary surgery (10), presence of lymph node metastases at initial diagnosis (3,(8)(9)(10)(11)(12), tumor multifocality (3,8,12) and capsular invasion (9,(11)(12)(13)(14...

show abstract

Section: Discussionmentioning

confidence: 99%

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

Nakamura

Onoda

Noda

et al. 2013

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…As BRAF V600E mutation is frequently found in tumors that are refractory to treatment with radioiodine (25) and small-molecule MAPK inhibitors restore the expression of thyroid-specific genes with consequent restoration of RAI uptake (61), it seems rational to explore whether BRAF V600E, NRAS Q61 or RET/PTC modulate the expression of proteins associated with iodine metabolism and may explain why some microPTC could be less responsive to RAI therapy and, therefore, RAI did not prevent the recurrence rate of some microPTC (59,62).…”

Section: :4mentioning

confidence: 99%

BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma

Bastos

Oler

Nozima

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

Background: Thyroid cancer incidence has dramatically increased worldwide over the last two decades. The rise is mostly due to an increased detection of small papillary thyroid carcinomas (PTCs) (%20 mm), predominantly microPTC (%10 mm). Although small tumors generally have an excellent outcome, a considerable percentage may have a more aggressive disease and worse prognosis. The clinical challenge is to preoperatively identify those tumors that are more likely to recur. Aim: To improve risk stratification and patient management, we sought to determine the prognostic value of BRAF V600E, NRAS or RET/PTC mutations in patients with PTC measuring !20 mm, mainly microPTC. Methods: The prevalence of RET/PTC fusion genes was examined by quantitative RT-PCR. BRAF V600E and NRAS Q61 mutations were determined by PCR sequencing. To further elucidate why some small PTC are less responsive to radioactive iodine treatment therapy, we explored if these genetic alterations may modulate the expression of iodine metabolism genes (NIS,TPO,TG,TSHR and PDS) and correlated with clinico-pathological findings that are predictors of recurrence. Results: This study shows that tumors measuring %20 mm exhibited higher prevalence of BRAF V600E mutation, which correlated with aggressive histopathological parameters, higher risk of recurrence, and lower expression of NIS and TPO. Although this correlation was not found when microPTC were evaluated, we show that tumors measuring 7-10 mm, which were positive for BRAF mutation, presented more aggressive features and lower expression of NIS and TPO. Conclusion: We believe that our findings will help to decide the realistic usefulness of BRAF V600E mutation as a preoperative marker of poor prognosis in small PTC, primarily in microPTC.

show abstract

“…Nowadays, there is a general agreement that LR DTC should not be submitted to RRA [8, 9] since a significant increase in disease-free survival or decrease in mortality has been demonstrated in these patients [10-14]. On the opposite, the use of RRA, usually with high activities of 131 I, is recommended for the management of high-risk patients in whom this procedure has shown a positive impact on recurrence and survival [15, 16].…”

Section: Introductionmentioning

confidence: 99%

Less than 2% of the Low- and Intermediate-Risk Differentiated Thyroid Cancers Show Distant Metastases at Post-Ablation Whole-Body Scan

et al. 2018

View full text Add to dashboard Cite

Background: Recently, there has been a trend to reduce the use of radioiodine remnant ablation (RRA) in patients with low-risk (LR) and intermediate-risk (IR) differentiated thyroid cancer (DTC). Objectives: The aim of this paper was to evaluate the diagnostic role of whole-body scan (ptWBS) performed after RRA in LR and IR DTC patients. Methods: We analyzed 545 DTC patients treated with total thyroidectomy and RRA in hypothyroidism followed by a ptWBS. Neck ultrasound (US) and serum thyroglobulin measurement were performed. According to the American Thyroid Association guidelines, patients were classified as LR (n = 345) and IR (n = 200). Results: In addition to the thyroid remnant, the ptWBS showed the presence of further areas of ¹³¹I uptake in 16/545 (2.9%) cases. ptWBS showed laterocervical lymph node metastases in 11/16 patients (10/11 were also detected by US), mediastinal uptake in 1/16, lung metastases in 3/16, and bone metastases in 1/16. Only 6/545 (1.1%) metastases were detected by ptWBS alone. After 7.8 years, 8/16 patients were free of disease, and 8 had persistent disease: 4 “biochemical” and 4 “structural.” Remission was achieved in 3 cases after one single ¹³¹I course, in 1 case after surgery, and in the last 4 cases after several ¹³¹I courses. Conclusions: The ptWBS diagnostic role was clinically relevant for the therapeutic strategies of our patients only in 1.1% of the cases. The cost-effectiveness of performing RRA and ptWBS in all LR and IR patients to find 1–2% of the cases with distant metastases remains controversial.

show abstract

Radioactive iodine ablation does not prevent recurrences in patients with papillary thyroid microcarcinoma

Cited by 72 publications

References 24 publications

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma

Less than 2% of the Low- and Intermediate-Risk Differentiated Thyroid Cancers Show Distant Metastases at Post-Ablation Whole-Body Scan

Contact Info

Product

Resources

About