Correspondence

Overdiagnosis and screening for thyroid cancer in Korea

The Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Station accident in March 2011 was rated as the most serious accident in the world and had an equivalent rating to the Chernobyl nuclear accident. As a result, there have been concerns about health hazards similar to that of the Chernobyl accident. The Fukushima Prefecture hence started the thyroid ultrasound examination (TUE) program after the accident and collected observations for an extended period of time. Screening for thyroid cancer using ultrasonography is not generally recommended for asymptomatic individuals who are not at risk of developing cancer because of the risk of overdiagnosis. Hence, in Japan, efforts to minimize this risk have been progressing, such as the initiation of the TUE program developed using Japanese diagnostic criteria. The subjects of the TUE program were Fukushima residents who were ≤ 18 years old at the time of the earthquake. They were scheduled to undergo examinations every 2 years until they reach 20 years old and every 5 years after 25. It was recommended that more detailed explanations should be offered in the prefectural expert meeting, despite the examinees and their families having been informed of the disadvantages as well as examination objectives in advance, and the examinations having been conducted after obtaining informed consent from the participants.

Malignant ovarian germ cell tumor (MOGCT) is a rare ovarian malignancy accounting for less than 5% of all ovarian cancers. We aimed to evaluate the incidence, survival, and subsequent malignancies after the diagnosis of MOGCT.

Data from the Korea Central Cancer Registry were used to identify MOGCTs between 1999 and 2017. The age-standardized rates (ASRs), 5-year relative survival rates (RSR) and standardized incidence ratio (SIR) for subsequent cancer after diagnosis of MOGCT were estimated.

Of 2125 cases of newly diagnosed MOGCTs, 596 (28.0%) were diagnosed with dysgerminoma and 1529 (72.0%) with non-dysgerminoma. The ASR per 100,000 women-years was 0.539; ASR slightly increased over the study period (annual percent change [APC] = 1.01%; p = 0.02). There was an increase and decrease in the incidence of MOGCTs in the age groups 0–19 years (APC = 1.96%; p < 0.01) and ≥ 50 years (APC = −6.51%; p < 0.01), respectively. Patients with dysgerminoma showed significantly higher RSR than patients with non-dysgerminoma (98.0% vs. 94.9%, p < 0.01). Patients aged ≥50 years showed worst 5-year RSR (68.7%) than patients aged 0–19 years (97.8%) and 20–34 years (96.4%) (p < 0.01). The overall SIR for a subsequent cancer occurrence was 2.07, with the most frequent site of subsequent primary cancer being the thyroid (SIR = 2.78).

Our data demonstrated an excellent prognosis of MOGCTs among Korean women. There was a slight increase in MOGCT prevalence, which was more pronounced among those aged <19 years. After MOGCT diagnosis, the risk of developing a subsequent malignancy was doubled compared with the general population.

The present study applied iTRAQ and LC-MS/MS techniques for proteome analysis and compared data between specimens of papillary thyroid microcarcinoma (PTMC) vs appropriate controls, in order to investigate the mechanisms underlying the invasion and metastasis process in PTMC development.

Fresh-tissue specimens were collected from 40 patients with thyroid disease who underwent surgical treatment. Specimens were divided into four groups: normal histology (NH; n = 8), benign thyroid tumor (BTT; n = 10), classic PTMC with lymph node metastasis (PTC-LNM⁽⁺⁾; n = 11), and classic PTMC without lymph node metastasis (PTC-LNM⁽⁻⁾; n = 11). Proteomic studies were conducted on PTMC tissue samples without capsule invasion and with tumor diameter ranging from 0.5 cm to 1 cm, so as to focus the study on PTMC development excluding metastasis.

A total of 8036 proteins were identified in the four groups. Based on protein function analysis, proteins that might be associated with PTMC invasion and metastasis were screened: alpha-actinin-1, alpha-1-antitrypsin, hepatoma-derived growth factor (HDGF), high-mobility group protein HMGI-C, and carbonic anhydrase 4. In addition, proteins involved in the focal adhesion pathway were examined. Immunohistochemistry confirmed the reliability of the iTRAQ results and the universality of differentially expressed proteins. The data showed that HDGF and high-mobility group protein HMGI-C are up-regulated in PTMC and that the focal adhesion pathway that promotes PTMC LNM is activated.

These findings provide insight into the mechanisms underlying PTMC invasion and metastasis.

Nous avons analysé le protéome d’échantillons de microcarcinome papillaire de la thyroïde (MCPT) grâce aux techniques iTRAQ (étiquette isobare pour la quantification relative et absolue) et LC-MS/MS (chromatographie en phase liquide couplée à la spectrométrie de masse) afin d’identifier les mécanismes de l’invasion et de la métastase du MCPT.

Des échantillons de tissu frais étaient pris sur 40 patients atteints d’une maladie de la thyroïde, qui ont subi un traitement initial et étaient ensuite divisés en 4 groupes : tissus histologiques normaux (HN ; n = 8), tissus présentant une tumeur de la thyroïde bénigne (TTB ; n = 10), tissus présentant un MCPT classique et des métastases ganglionnaires (CPT-MG⁽⁺⁾ ; n = 11), tissus présentant un MCPT classique sans métastases ganglionnaires (CPT-MG⁽⁻⁾ ; n = 11). Les études des différents protéomes ont été réalisées sur des tissus atteints de MCPT sans invasion capsulaire, prélevés dans des carcinomes uniques de diamètre 0,5–1 cm. Ceci exclut les facteurs anatomiques de métastase, fournissant ainsi des informations sur les changements biologiques au niveau moléculaire impliqués dans le MCPT.

Au total, 8036 protéines ont été identifiées au sein des 4 groupes. À partir de l’analyse de la fonction de ces protéines, celles pouvant être associées à l’invasion et la métastase du MCPT ont été identifiées : alpha-actinine-1, alpha-1-antitrypsine, facteur de croissance dérivé de l’hépatome (HDGF), protéine du groupe de haute mobilité HMGI-C et l’anhydrase carbonique-4. De plus, la voie d’adhésion focale est peut-être impliquée dans l’invasion et la métastase du MCPT. Les techniques d’immunohistochimie ont confirmé la fiabilité des résultats obtenus par la technique iTRAQ ainsi que l’universalité des protéines à expression différentielle.

Cette étude démontre que la surexpression du facteur HDGF et de la protéine du groupe de haute mobilité HMGI-C est présente dans les MCPT et que l’activation de la voie d’adhésion focale pourrait favoriser l’apparition de métastases ganglionnaires. Ces résultats devraient améliorer la compréhension des mécanismes de l’invasion et de la métastase du MCPT.

To establish the long term outcomes of risk stratified management of differentiated thyroid cancer (DTC).

Guidelines for management of DTC lack a strong evidence base and expose patients to overtreatment. This prospective study of patients diagnosed with DTC between 1977 and 2012 describes the long term outcomes of a conservative risk stratified (AMES) management policy.

Outcomes were analysed around patient and tumour characteristics, primary intervention (surgery ± radioiodine (RAI)), in terms of mortality, recurrence and reintervention.

Median follow-up in 348 patients was 14 years: mean age 48 (range 10–91) years, 257 (73.9%) female, 222 (68.3%) papillary cancer, tumour size 3.4 ± 2.0 cm (mean ± SD). 89 (25.6%) AMES high risk, 116 (33.3%) TNM stage III/IV and 16 (4.6%) had distant metastases. Primary surgery comprised lobectomy in 189 (54.3%): 11 (5.8%) patients had subsequent completion total thyroidectomy with cancer present in five. Primary nodal surgery was performed in 142 (40.8%) patients. 35 (13.5%) low and 43 (48.3%) high risk patients received RAI following initial surgery. Overall disease specific survival (DSS) was 92.1% at 10 years and 90.7% at 20 years. DSS at 20 years was 99.2% in low risk cases. AMES risk scoring predicted both survival and recurrence. Patients receiving RAI and AMES high risk were significantly associated with increased risk of death and recurrence.

Routine total thyroidectomy and RAI are not justifiable for low risk DTC. Treatment should be tailored to risk and AMES risk stratification remains a simple reliable clinical tool.