The Relationship of Immunoexpression of Ki-67 and Hsp70 with Clinical and Morphological Parameters and Prognosis of Papillary Thyroid Cancer

Avdalyan, A. M.; Ivanov, A A; Лушникова, Е. Л.; Молодых, О. П.; Vikhlyanov, I. V.

doi:10.1007/s10517-020-04781-1

Cited by 12 publications

(7 citation statements)

References 13 publications

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“…It is noteworthy that the BRAF V600E -positive PTCs were associated with the smaller tumor size and the higher Ki67 LI, although there was no evidence of a direct link between these two parameters in this group. Several previous works have reported elevated KI67 LI in the BRAF V600E -positive PTCs in adult patients ( 48 , 49 ), and a positive correlation between KI67 LI and PTC size ( 48 , 50 – 52 ). The BRAF V 600 E mutation was also associated with greater tumor size [meta-analyses ( 18 , 20 ), although not in all studies ( 24 )].…”

Section: Discussionmentioning

confidence: 79%

Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident

et al. 2022

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With time after the Chernobyl accident, the number of papillary thyroid carcinomas (PTCs) driven by the BRAFV600E oncoprotein is growing in patients exposed to radiation at a young age. Clinicopathological associations of BRAFV600E in PTCs from patients with internal radiation history have not been sufficiently studied so far. This work analyzes the structural characteristics, proliferative activity, invasive features, clinical information, and dosimetric data in the BRAFV600E-positive and BRAFV600E-negative PTCs from the Ukrainian patients exposed to Chernobyl radiation and treated over 30 years after the accident. The study included 428 PTCs from patients aged 4–49 years at surgery who lived in the six northern regions of Ukraine most contaminated by 131I, were ≤18 years of age at the time of exposure, and were operated on from 1990 to 2017. Immunohistochemical staining for BRAFV600E was performed with the VE1 antibody. The probability of causation (POC) of a tumor due to radiation was determined using an interactive online NIH/NCI software. BRAFV600E was detected in 136/428 (31.8%) PTCs. In comparison with the BRAFV600E-negative PTCs, the BRAFV600E-positivity was associated with older patient age at the accident and at surgery, a longer period of latency, and lower POC. The BRAFV600E-positive PTCs were characterized by smaller tumor size, higher Ki67 labeling index, more frequent oncocytic changes, multifocality, and dominant papillary growth pattern. Tumor invasive features were less frequent in the BRAFV600E-positive PTCs and did not change with POC level. Despite a less aggressive tumor phenotype, BRAFV600E was a risk factor for recurrence, namely radioiodine-refractory (RAI-R) recurrent metastases. Multivariate models of RAI-R included BRAFV600E and/or histopathological parameters closely correlating with BRAFV600E such as tumor size, multifocality, dominant papillary growth pattern, or oncocytic changes. Thus, the BRAFV600E-positive PTCs from patients from a high-risk group for radiogenic thyroid cancer diagnosed in the 30 years after the Chernobyl accident did not display higher invasiveness regardless of POC level, but in view of the prognostic impact of this genetic alteration, knowledge of the BRAF status may be beneficial for middle-aged patients with radiogenic PTC considered for RAI therapy, and suggests more careful follow-up of patients with the BRAFV600E-positive tumors.

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Section: Discussionmentioning

confidence: 79%

Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident

et al. 2022

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“…Such a correlation was reported in adult PTC patients [ 18 , 41 ] but no data are available for young patients. In general, the higher Ki67 LI was associated with the greater size of PTCs in adult patients [ 18 , 42 , 43 , 44 ] and poorer prognosis [ 30 , 45 , 46 , 47 ]. The BRAF V600E mutation was also associated with the greater tumor size in some studies (meta-analyses [ 34 , 35 ]), although equivocally [ 24 , 27 , 28 ] (meta-analysis [ 39 ]), and with higher tumor aggressiveness (meta-analyses [ 29 , 34 , 35 , 36 , 38 , 39 , 48 ]).…”

Section: Discussionmentioning

confidence: 99%

The BRAFV600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age

Zurnadzhy

Bogdanova

Rogounovitch

et al. 2021

Cancers

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Histopathological changes in the fusion oncogene-driven papillary thyroid carcinomas (PTCs) from children and adolescents exposed to Chernobyl fallout have been extensively studied. However, characteristics of the radiogenic BRAFV600E-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAFV600E status (determined immunohistochemically with the VE1 antibody) and the clinicopathological features of 247 radiogenic and 138 sporadic PTCs from young Ukrainian patients aged ≤28 years. The frequency of BRAFV600E was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAFV600E-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAFV600E-negative tumors. Comparison of the BRAFV600E-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAFV600E-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAFV600E-negative sporadic tumors. Thus, BRAFV600E is not associated with a more aggressive course of PTC in young patients regardless of etiology. The major clinicopathological differences between the radiogenic and sporadic PTCs are observed among the BRAFV600E-negative tumors.

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“…HSP70, a member of the HSP family, has been reported to be highly expressed in numerous types of cancer and is associated with higher tumour grade, metastasis, chemotherapeutic resistance and poor prognosis (38,39). Nuclear translocation and expression of the HSP70 protein is correlated with the stage and the prognosis of patients with papillary thyroid cancer (40). The overall survival rates of patients with nasopharyngeal carcinoma with positive expression of HSP70 were significantly lower than those with negative expression (41).…”

Section: Discussionmentioning

confidence: 99%

Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis

et al. 2021

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Adrenocortical carcinoma (ACC) is an endocrine tumour with high malignancy, high invasiveness and poor prognosis. Curcumin, a major component in turmeric, has been reported to have good efficacy and biological safety in treating cancer. However, the role and mechanism of curcumin in ACC have not yet been fully investigated and were thus the focus of this study. In vitro, ACC SW-13 and NCI-H295R cells were treated with curcumin and their viability, migration and invasion were assessed by CCK-8 and Transwell assays. Apoptosis was detected via flow cytometry and western blotting. High-throughput sequencing and comprehensive bioinformatics analyses were performed to elucidate the molecular processes underlying curcumin activity. In vivo, SW-13 cells were injected into nude mice, and the tumour volumes and weights were observed after 2 weeks of curcumin treatment. Organelle changes were observed by electron microscopy, and potential candidate genes and pathways were analysed by RT-qPCR and western blotting. The role of the C/EBP homologous protein (CHOP) target gene in curcumin-induced ACC cell apoptosis was verified via lentiviral transfection experiments. Curcumin inhibited the viability, migration and invasion, and induced the apoptosis of ACC cells. Transcriptome sequencing analysis showed that curcumin treatment markedly changed the gene expression levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the MAPK and endoplasmic reticulum (ER) stress pathways were the predominant pathways associated with curcumin-induced apoptosis of ACC cells. Subsequent in vivo and in vitro results demonstrated that the JNK, p38 MAPK and ER stress pathways were activated in curcumin-treated ACC cells, and that CHOP induction was responsible for curcumin-induced apoptosis of ACC cells. In summary, curcumin induced ACC cell apoptosis and inhibited tumour growth by activating the JNK, p38 MAPK and ER stress pathways. Thus, curcumin may be a potential therapeutic drug for ACC.

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The Relationship of Immunoexpression of Ki-67 and Hsp70 with Clinical and Morphological Parameters and Prognosis of Papillary Thyroid Cancer

Cited by 12 publications

References 13 publications

Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident

Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident

The BRAFV600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age

Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis

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