Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Hsu, Yi Chiung; Lee, Jie Jen; Chien, Ming Nan; Chen, Ming Jen; Leung, Ching Hsiang; Cheng, Shih‐Ping

doi:10.1002/jso.25670

Cited by 10 publications

(9 citation statements)

References 37 publications

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“…To reinforce our results, the thyroid cancer (THCA) data set of The Cancer Genome Atlas (TCGA) was analysed [22]. The mRNA expression of CHI3L1 was positively associated with extrathyroidal extension (p < 0.001, Figure 1C), lymph node metastasis (p < 0.001), and TNM stage (p < 0.001).…”

Section: High Chi3l1 Expression Is Associated With a Greater Recurrensupporting

confidence: 58%

Overexpression of chitinase‐3‐like protein 1 is associated with structural recurrence in patients with differentiated thyroid cancer

Cheng

Lee

Chang

et al. 2020

The Journal of Pathology

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We previously identified that the expression of chitinase‐3‐like protein 1 (CHI3L1) was upregulated during thyroid cancer progression. Here, we investigated the prognostic significance of CHI3L1 expression in thyroid neoplasms and examined the potential oncogenic roles. CHI3L1 immunochemical staining was performed on tissue microarrays of benign and malignant thyroid tumours. Compared with normal thyroid tissue and benign thyroid lesions that had low or no detectable CHI3L1 expression, CHI3L1 was overexpressed in both differentiated and undifferentiated thyroid cancer. High CHI3L1 expression was associated with extrathyroidal extension, lymph node metastasis, and shorter recurrence‐free survival in differentiated thyroid cancer. The biological roles of CHI3L1 were further investigated by gain‐ and loss‐of‐function assays. CHI3L1 silencing suppressed clonogenicity, migration, invasion, anoikis resistance, and angiogenesis in thyroid cancer cells, although exogenous CHI3L1 treatment promoted these malignant phenotypes. Cysteine‐rich angiogenic inducer 61 (CYR61) was identified as a downstream target of CHI3L1 by RNA‐seq analysis. CYR61 silencing or treatment reversed the alterations induced by CHI3L1 modulation. Our results demonstrate that CHI3L1 is overexpressed in thyroid cancer and is associated with an increased risk of disease recurrence. Additionally, CYR61 may participate in CHI3L1‐mediated tumour progression. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: High Chi3l1 Expression Is Associated With a Greater Recurrensupporting

confidence: 58%

Overexpression of chitinase‐3‐like protein 1 is associated with structural recurrence in patients with differentiated thyroid cancer

Cheng

Lee

Chang

et al. 2020

The Journal of Pathology

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“…There is strong evidence that multifocality is a marker of extensive disease instead of an independent prognostic factor for PTC 9 . However, it is necessary to investigate the clinical and prognostic implications of multifocality on PTMC, based on the consensus that PTMC has different genetic characteristics, 21 biological behaviour and corresponding clinical management compared with PTC 10,11 . In fact, some studies have focused on the role of multifocality and its bilaterality in the aggression and prognosis of PTMC 7,8,12,13,16,17 .…”

Section: Discussionmentioning

confidence: 99%

“…and UFD PTMC patients matched for propensity scores different genetic characteristics, 21 biological behaviour and corresponding clinical management compared with PTC. 10,11 In fact, some studies have focused on the role of multifocality and its bilaterality in the aggression and prognosis of PTMC.…”

Section: Ta B L E 3 Comparison Of Aggressive Variables Between B-mfd or U-mfdmentioning

confidence: 99%

Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: A propensity score matching analysis

Yan

Qiu

Song

et al. 2021

Clinical Endocrinology

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Context Multifocality and bilaterality are common in patients with papillary thyroid microcarcinoma (PTMC). However, their clinical behaviours and prognostic implications remain controversial. Objective To investigate the relationship between multifocality and classically aggressive characteristics and outcomes in patients with PTMC. Methods Clinical data of 3005 patients with PTMC were retrospectively reviewed at a tertiary medical centre. The role of unilateral and bilateral multifocality in aggressive characteristics and clinical outcomes of PTMC was evaluated using propensity score matching (PSM). Results A total of 573 patients had bilateral multifocal disease (B‐MFD), 272 had unilateral multifocal disease (U‐MFD), and 2160 had unifocal disease (UFD). Univariate analysis showed that patients in the multifocal disease (MFD) groups showed significantly different characteristics compared to patients in the UFD group in terms of age, chronic lymphocytic thyroiditis (CLT), follicular variant PTMC, tumour diameter, aggressive growth, including extrathyroidal extension (ETE), central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM), and TNM stage, and underwent radioactive iodine (RAI) therapy. Further stratified analysis revealed that patients in the B‐MFD group reflected the differences between the MFD and UFD groups. However, those in the U‐MFD group showed slight differences only in sex, CLT and cell subtypes, compared to the UFD group. In addition, PSM indicated differences in ETE, CLNM and LLNM between the B‐MFD and UFD groups (p < .001), while only ETE differed between the U‐MFD and UFD groups (p < .001). After a median follow‐up period of 60 months, no difference was observed in recurrence‐free survival between the UFD and B‐MFD (p = .294) or U‐MFD (p = .603) groups using PSM. Conclusion This propensity score matching analysis provides strong evidence that bilateral multifocality, rather than unilateral multifocality, should be considered as an aggressive marker at presentation, and neither is an independent prognostic factor for clinical outcome in PTMC.

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“…Most authors agree that mPTCs are not "early stage" PTCs, but rather they constitute old lesions that are prone to remain quiescent for years. In fact, even though mPTCs are usually considered to be histologically and biologically similar to PTCs, two groups [3,4] showed that mPTCs display a different gene expression pattern from PTCs and hypothesised that tumour microenvironment could play a role in this phenotypic divergence.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation and clinical correlation of papillary thyroid microcarcinoma

et al. 2020

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Purpose Papillary thyroid microcarcinoma (mPTC) is defined as a papillary thyroid cancer sized 10 mm or less. Despite their generally indolent clinical course and good prognosis, a subset of mPTCs shows potentially aggressive behaviour. Methods To search for predictors of clinical outcome of mPTCs, we retrospectively evaluated the genetic tumour profile of 100 patients (23 M/77 F, mean age ± SD 53.8 ± 13.4 years) with histologically confirmed mPTCs through analysis of BRAF, NRAS and TERT promoter mutations as well as RET/PTC translocations. Results Mean follow-up period was 8.4 ± 3.6 years. In 55 cases, mPTC were detected incidentally after surgery. Capsular invasion, bilateralism and multifocality were found in 11/100, 17/100 and 24/100 cases, respectively, while lymph-nodes metastases were present at diagnosis in 9/100 cases. After 3.5 ± 2.0 years, tumour relapse occurred in 6/100 cases and was locoregional in five (two in the thyroid bed, three in laterocervical lymph-nodes), while lung metastasis occurred in one case. Biochemical persistence of disease was seen in 1/100 case. Mutations occurred in 55/100 cases; BRAF V600E was the most frequently detected (49/100) and was associated with higher tumour size, bilateralism and follicular variant but not with capsular invasion. RET/PTC rearrangements were found in 2/100 cases, NRAS Q61R in 4/100, while no mutations of TERT promoter gene were detected. Despite the observed association between BRAF V600E mutation and unfavourable histopathological features, we found no direct association with tumour recurrence, distant metastases and mortality. Conclusion In our study, the search for the most frequent genetic alterations as prognostic markers in mPTCs would not have changed the therapeutic strategy.

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Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Cited by 10 publications

References 37 publications

Overexpression of chitinase‐3‐like protein 1 is associated with structural recurrence in patients with differentiated thyroid cancer

Overexpression of chitinase‐3‐like protein 1 is associated with structural recurrence in patients with differentiated thyroid cancer

Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: A propensity score matching analysis

Molecular characterisation and clinical correlation of papillary thyroid microcarcinoma

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