Publications by authors named "Małgorzata Oczko-Wojciechowska"

51 Publications

Thyroid nodules with indeterminate cytopathology: a constant challenge in everyday practice. The effectiveness of clinical decisions using diagnostic tools available in Poland.

Pol Arch Intern Med 2021 Oct 11. Epub 2021 Oct 11.

Introduction: A crucial issue in the management of thyroid nodules is to estimate, as accurately as possible, the malignancy risk in thyroid lesions. The key tool for risk stratification is fine needle aspiration biopsy. Unfortunately, approximately 20 % of biopsy results are indeterminate. The malignancy risk assigned to these categories does not allow unequivocal further management.

Objectives: We aimed to assess the malignancy risk in indeterminate thyroid nodules in the Polish population, and to analyze the effectiveness of clinical decisions after an indeterminate cytological diagnosis in Polish clinical practice.

Patients And Methods: The retrospective analysis included 222 indeterminate thyroid nodules in 222 patients. The ultrasound features were assessed from scans preceding a thyroid biopsy. Cytology results were classified according to the Bethesda system. The nature of the thyroid nodule was determined on the basis of a histopathological analysis or follow up.

Results: The analyzed cohort included 82 lesions in Bethesda category III, 75 in Bethesda category IV and 65 in Bethesda category V. The malignancy risk, estimated on the basis of histological verification and surveillance was 6.7% for Bethesda III, 11.3% for Bethesda IV and 70.3%for Bethesda V category. An ultrasound pattern was not effective enough for refining the malignancy risk after obtaining an indeterminate cytopathology result. In the case of surgery, postoperative hypoparathyroidism was significantly more frequent following more extensive surgical procedures.

Conclusions: Majority of Polish patients with thyroid nodules assigned to cytological categories Bethesda III and IV is overtreated using diagnostic tools currently available in Poland.
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http://dx.doi.org/10.20452/pamw.16117DOI Listing
October 2021

Therapeutic Strategy in Low-Risk Papillary Thyroid Carcinoma - Long-Term Results of the First Single-Center Prospective Non-Randomized Trial Between 2011 and 2015.

Front Endocrinol (Lausanne) 2021 6;12:718833. Epub 2021 Sep 6.

Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

Optimal therapeutic strategy in low advanced papillary thyroid carcinoma (PTC) is still a matter of debate. The management differs depending on the country. A prospective non-randomized study was performed to evaluate whether less extensive surgery could be a safe, acceptable, and sufficient therapeutic option in PTC cT1N0M0 patients. The present paper summarizes the results of over a 5-year follow-up.

Material: Our prospective group (PG) treated between 2011 and 2015 consisted of 139 patients with cT1aN0M0 PTC who underwent lobectomy (LT) as initial surgical treatment (PGcT1aN0M0 group) and 102 cT1bN0M0 patients in whom total thyroidectomy (TT) with unilateral central neck dissection (CND) was performed (PGcT1bN0M0). PG was compared with the retrospective group (RG) of patients who underwent TT with bilateral CND between 2004 and 2006: 103 cT1aN0M0 patients (RGcT1aN0M0) and 91cT1bN0M0 (RGcT1bN0M0). The risks of reoperation, cancer relapse and postoperative complications were analyzed.

Results: Only 12 cT1aN0M0 patients (7.6%) withdrew from the trial and underwent TT with bilateral CND. Over 90% of patients accepted less extensive surgery. In 4 cT1aN0M0 cases, TT with CND was performed due to lymph node metastases found intraoperatively. The initial clinical stage according to the TNM/AJCC 7 edition was confirmed histologically in 77% of cases in PGT1aN0M0 and in 72% in PGT1bN0M0, respectively. 24 PGcT1aN0M0 patients were reoperated on. In this group, cancer lesions in the postoperative histological specimens were found in 8 cases (32%). Five-year disease-free survival (DFS) was excellent. However, no statistically significant differences were found between PG and RG groups (99.3% in PGcT1aN0M0 and 99.0%, in RGcT1aN0M0; p = 0.41 and 98%, in PGcT1bN0M0 and 94.4% in RGcT1bN0M0; p=0.19). No significant differences were observed in the incidence of early paresis of the recurrent laryngeal nerves between PG and RG. However, as predicted, LT completely eliminated the risk of postoperative hypoparathyroidism.

Summary: The results of the prospective clinical trial confirm that less extensive surgery in adequately selected low-advanced PTC patients is both safe and sufficient.
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http://dx.doi.org/10.3389/fendo.2021.718833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450606PMC
September 2021

variants of uncertain significance in clinical practice: A case report.

Mol Clin Oncol 2021 Nov 31;15(5):222. Epub 2021 Aug 31.

The Department of Genetic and Molecular Diagnostics of Cancer, Maria Sklodowska-Curie, National Research Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland.

The influence of variants of uncertain significance (VUSs) on the cancer risk and their association with the response to treatment is uncertain. The aim of the present study was to evaluate the role of VUS in patients with breast cancer. A total of two cases of breast cancer patients with the VUS were described. The complete coding sequence of genes was analyzed from the genomic DNA material by next generation sequencing on the Ion Torrent platform. The presence of c.3454G>A (p.Asp1152Asn) VUS in the gene was reported in a 64-year-old woman with invasive breast carcinoma. The characteristics of the breast tumors were the following: moderately differentiated-intermediate grade (NG-2 G-2), HER2 (+), estrogen receptor (ER) (+++), progesterone receptor (PR) (+++), luminal A subtype and pT2 N1a Mx. The second detected VUS was the c.2374T>C (p.Tyr792His) variant in the gene. This variant was reported in a 33-year-old woman who was diagnosed with right breast cancer (cT2N1M0). The invasive breast carcinoma was characterized as follows: NG-2 G-2, ER (+++), PR (+++), Ki-67 10%, HER2 (+++) and luminal B subtype. The data demonstrated that patients with VUSs should be managed based on their family history of cancer and clinicopathological characteristics. The clinical significance of the VUS in may change over time and reclassification of the variant to 'pathogenic' or 'benign' should be undertaken. Patients with VUS should be followed up regularly.
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http://dx.doi.org/10.3892/mco.2021.2385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447178PMC
November 2021

Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma.

Int J Mol Sci 2021 Jun 23;22(13). Epub 2021 Jun 23.

Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Marymoncka 99/103, 01-813 Warsaw, Poland.

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., V600E mutation) is associated with the activity of FRMD5.

Methods: The studies were conducted on TPC1 and BCPAP ( V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of . The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the expressional status.

Results: The obtained data indicate that the expression of is significantly enhanced in V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both -wt and -mutated PTC cells were observed. It was also found that knockdown of significantly alters the expression of multidrug resistant genes.

Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.
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http://dx.doi.org/10.3390/ijms22136726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268710PMC
June 2021

A Direct Comparison of Patients With Hereditary and Sporadic Pancreatic Neuroendocrine Tumors: Evaluation of Clinical Course, Prognostic Factors and Genotype-Phenotype Correlations.

Front Endocrinol (Lausanne) 2021 28;12:681013. Epub 2021 May 28.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland.

Introduction: Pancreatic neuroendocrine tumors (PNETs) in hereditary syndromes pose a significant challenge to clinicians. The rarity of these syndromes and PNETs itself make it difficult to directly compare them with sporadic PNETs. Despite research suggesting differences between these two entities, the same approach is used in hereditary and sporadic PNETs.

Methods: We included 63 patients with hereditary PNET (GpNET) and 145 with sporadic PNET (SpNET) in a retrospective observational study. Clinical and genetic data were collected in two Polish endocrine departments from January 2004 to February 2020. Only patients with confirmed germline mutations were included in the GpNET cohort. We attempted to establish prognostic factors of metastases and overall survival in both groups and genotype-phenotype correlations in the GpNET group.

Results: Patients with GpNET were younger and diagnosed earlier, whereas their tumors were smaller and more frequently multifocal compared with patients with SpNET. Metastases occurred more frequently in the SpNET group, and their appearance was associated with tumor size in both groups. GpNET patients had longer overall survival (OS). OS was affected by age, age at diagnosis, sex, grade, stage, tumor diameter, occurrence and localization of metastases, type of treatment, and comorbidities. In the MEN1 group, carriers of frameshift with STOP codon, splice site, and missense mutations tended to have less advanced disease, while patients with mutations in exon 2 tended to have metastases more frequently.

Conclusions: Direct comparisons of GpNET and SpNET demonstrate significant differences in the clinical courses of both entities, which should force different approaches. A larger group of patients with GpNET should be assessed to confirm genotype-phenotype correlations.
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http://dx.doi.org/10.3389/fendo.2021.681013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194819PMC
May 2021

Shared and unique metabolic features of the malignant and benign thyroid lesions determined with use of H HR MAS NMR spectroscopy.

Sci Rep 2021 01 14;11(1):1344. Epub 2021 Jan 14.

Department of Medical Physics, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102, Gliwice, Poland.

The purpose of this work was to investigate the distinct and common metabolic features of the malignant and benign thyroid lesions in reference to the non-transformed tissue from the contralateral gland (chronic thyroiditis and colloid goiter). H HR MAS NMR spectra of 38 malignant lesions, 32 benign lesions and 112 samples from the non-tumoral tissue (32 from chronic thyroiditis and 80 samples from colloid goiter) were subjected both to multivariate and univariate analysis. The increased succinate, glutamine, glutathione, serine/cysteine, ascorbate, lactate, taurine, threonine, glycine, phosphocholine/glycerophosphocholine and decreased lipids were found in both lesion types in comparison to either colloid goiter or chronic thyroiditis. The elevated glutamate and choline, and reduced citrate and glucose were additionally evident in these lesions in reference to goiter, while the increased myo-inositol-in comparison to thyroiditis. The malignant lesions were characterized by the higher alanine and lysine levels than colloid goiter and thyroiditis, while scyllo-inositol was uniquely increased in the benign lesions (not in cancer) in comparison to both non-tumoral tissue types. Moreover, the benign lesions presented with the unique increase of choline in reference to thyroiditis (not observed in the cancerous tissue). The metabolic heterogeneity of the non-tumoral tissue should be considered in the analysis of metabolic reprogramming in the thyroid lesions.
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http://dx.doi.org/10.1038/s41598-020-79565-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809111PMC
January 2021

Laparoscopic cortical-sparing adrenal surgery in pheochromocytomas associated with hereditary neoplasia syndromes.

Endokrynol Pol 2020 30;71(6):518-523. Epub 2020 Oct 30.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland.

Introduction: Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas.

Material And Methods: We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3-1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5-4 years).

Results: No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved.

Conclusions: In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.
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http://dx.doi.org/10.5603/EP.a2020.0075DOI Listing
October 2021

Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival.

Front Endocrinol (Lausanne) 2020 6;11:571421. Epub 2020 Oct 6.

Department of Nuclear Medicine and Endocrine Oncology, M.Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

We are witnessing a rapid worldwide increase in the incidence of papillary thyroid carcinoma (PTC) in the last thirty years. Extensive implementation of cancer screening and wide availability of neck ultrasound or other imaging studies is the main reason responsible for this phenomenon. It resulted in a detection of a growing number of clinically asymptomatic PTCs, mainly low-risk tumors, without any beneficial impact on survival. An indolent nature of low-risk PTC, particularly papillary thyroid microcarcinoma (PTMC), and the excellent outcomes raise an ongoing discussion regarding the adequacy of treatment applied. The question of whether PTMC is overtreated or not is currently completed by another, whether PTMC requires any treatment. Current ATA guidelines propose less extensive preoperative diagnostics and, if differentiated thyroid cancer is diagnosed, less aggressive surgical approach and limit indications for postoperative radioiodine therapy. However, in intrathyroidal PTMCs in the absence of lymph node or distant metastases, active surveillance may constitute alternative management with a low progression rate of 1%-5% and without any increase in the risk of poorer outcomes related to delayed surgery in patients, in whom it was necessary. This review summarizes the current knowledge and future perspectives of active surveillance in low-risk PTC.
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http://dx.doi.org/10.3389/fendo.2020.571421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573306PMC
May 2021

Current status of the prognostic molecular markers in medullary thyroid carcinoma.

Endocr Connect 2020 Dec;9(12):R251-R263

Nuclear Medicine and Endocrine Oncology Department, M. Sklodowska-Curie Institute National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

Medullary thyroid cancer (MTC) is a rare thyroid malignancy, which arises from parafollicular C-cells. It occurs in the hereditary or sporadic form. Hereditary type is a consequence of activation of the RET proto-oncogene by germline mutations, whereas about 80% of sporadic MTC tumors harbor somatic, mainly RET or rarely RAS mutations. According to the current ATA guidelines, a postoperative MTC risk stratification and long-term follow-up are mainly based on histopathological data, including tumor stage, the presence of lymph node and/or distant metastases (TNM classification), and serum concentration of two biomarkers: calcitonin (Ctn) and carcinoembryonic antigen (CEA). The type of RET germline mutation also correlates with MTC clinical characteristics. The most common and the best known RET mutation in sporadic MTC, localized at codon 918, is related to a more aggressive MTC course and poorer survival. However, even if histopathological or clinical features allow to predict a long-term prognosis, they are not sufficient to select the patients showing aggressive MTC courses requiring immediate treatment or those, who are refractory to different therapeutic methods. Besides the RET gene mutations, there are currently no other reliable molecular prognostic markers. This review summarizes the present data of genomic investigation on molecular prognostic factors in medullary thyroid cancer.
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http://dx.doi.org/10.1530/EC-20-0374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774764PMC
December 2020

Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma-Do They Exist?

Int J Mol Sci 2020 Jun 29;21(13). Epub 2020 Jun 29.

Nuclear Medicine and Endocrine Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-101 Gliwice, Poland.

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A-U133, set B-HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: (most significant) and . However, when analyzed on an independent dataset by qPCR, the gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.
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http://dx.doi.org/10.3390/ijms21134629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369779PMC
June 2020

Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma.

Cancers (Basel) 2020 Jun 17;12(6). Epub 2020 Jun 17.

Department of Genetic and Molecular Diagnostics of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-102 Gliwice, Poland.

Background: Telomerase reverse transcriptase promoter (p) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of p mutations in PTC was the aim of our study.

Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. V600E, and p mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(-) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis.

Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(-) PTCs. Deregulation of pathways involved in key cell processes was observed.

Conclusions: p mutations are related to higher PTC aggressiveness. gene was validated as associated with p mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.
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http://dx.doi.org/10.3390/cancers12061597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352936PMC
June 2020

Impact of the Tumor Microenvironment on the Gene Expression Profile in Papillary Thyroid Cancer.

Pathobiology 2020 22;87(2):143-154. Epub 2020 Apr 22.

Nuclear Medicine and Endocrine Oncology Department, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

Transcriptome of papillary thyroid cancer (PTC) is well characterized and correlates with some prognostic and genotypic factors, but data addressing the interaction between PTC and tumor microenvironment (TME) are scarce. Therefore, in the present study, we aimed to assess the impact of TME on gene expression profile in PTC. We evaluated the gene expression profile in PTC and normal thyroid cells isolated by laser capture microdissection and in whole tissue slides corresponding to the entire tumor. We included 26 microdissected samples for gene expression analysis (HG-U133 PLUS 2.0, Affymetrix, currently Thermo Fisher Scientific USA): 15 PTC samples, 11 samples of normal thyrocytes, and 30 whole slides (15 PTC and 15 normal thyroid). Transcripts were divided into three groups: differentially expressed both in microdissected and whole slides, transcripts differently expressed in microdissected samples and not changed in whole slides, and transcripts differentially expressed in whole slides and not changed in microdissected samples. Eleven genes were selected for validation in an independent set of samples; among them, four genes differentiated only microdissected PTC and normal cells. Two genes (PTCSC and CTGF) were confirmed. One gene (FOS) was not confirmed by the validation, whereas EGR1 was also significant in whole slide analysis. The other seven genes (TFF3, FN1, MPPED2, MET, KCNJ2, TACSTD2, and GALE) showed differentiated expression in microdissected thyrocytes and in whole tumor slides. Most of identified genes were related to the tumor-microenvironment interaction and confirmed the crosstalk between TME and cancer cells.
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http://dx.doi.org/10.1159/000507223DOI Listing
April 2021

European perspective on the use of molecular tests in the diagnosis and therapy of thyroid neoplasms.

Gland Surg 2020 Feb;9(Suppl 2):S69-S76

The Oncologic and Reconstructive Surgery Clinic, Maria Sklodowska-Curie Institute-Oncology Center, Gliwice Branch, Gliwice, Poland.

Thyroid nodules are frequently observed, particularly in individuals of over 60 years of age. On the other hand, most of the detected changes are benign and they do not require surgery. Therefore, differentiation between benign and malignant lesions in preoperative diagnosis is of crucial importance. Currently, the use of fine-needle aspiration biopsy (FNAB) and cytological assessment are the gold standard in the diagnosis of thyroid nodules. This procedure significantly reduces the need for diagnostic surgical intervention. However, approximately 15-30% of cytological results are classified as indeterminate. This is mainly due to the lack of specific cytomorphologic features that would facilitate the diagnosis based on cell evaluation under microscopic assessment. For the diagnoses of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), the assessment of invasion is crucial. Such an evaluation is not possible in cytology. Recently, molecular tests have been developed. They improve cytological diagnosis, particularly in the case of indeterminate results. Commercially available tests are developed based on the North American population. It is important to assess whether such tests can be used in the evaluation of e.g., European population.
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http://dx.doi.org/10.21037/gs.2019.10.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044080PMC
February 2020

Current surgical management in RET mutation carriers [Aktualne postępowanie chirurgiczne u nosicieli mutacji proto-onkogenu RET].

Endokrynol Pol 2019 ;70(4):367-379

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute - Oncology Centre Gliwice Branch, Gliwice, Poland.

Medullary thyroid carcinoma (MTC) still remains a rare endocrine tumor. 20-25% of MTC cases are genetically determined. The detection of the RET proto-oncogene mutation in 1993 allowed to understand the unique genotype-phenotype relationships in hereditary medullary thyroid carcinoma (HMTC) and formed the basis for therapeutic decisions based on the molecular results. Currently, prophylactic thyroidectomy is a commonly adopted and accepted therapeutic method. The decision on the time and extent of surgery should be made based on the results of molecular examination, the assessment of calcitonin (Ct) concentration and family history. Treatment of patients with HMTC requires the cooperation of a multidisciplinary team of experts and should be done in specialized centers only. The study is a review of the current guidelines for surgical management in the MEN2 syndrome.
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http://dx.doi.org/10.5603/EP.a2019.0021DOI Listing
February 2020

Novel TG-FGFR1 and TRIM33-NTRK1 transcript fusions in papillary thyroid carcinoma.

Genes Chromosomes Cancer 2019 08 18;58(8):558-566. Epub 2019 Feb 18.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute - Oncology Center Gliwice Branch, Gliwice, Poland.

Papillary thyroid carcinoma (PTC) is most common among all thyroid cancers. Multiple genomic alterations occur in PTC, and gene rearrangements are one of them. Here we screened 14 tumors for novel fusion transcripts by RNA-Seq. Two samples harboring RET/PTC1 and RET/PTC3 rearrangements were positive controls whereas the remaining ones were negative regarding the common PTC alterations. We used Sanger sequencing to validate potential fusions. We detected 2 novel potentially oncogenic transcript fusions: TG-FGFR1 and TRIM33-NTRK1. We detected 4 novel fusion transcripts of unknown significance accompanying the TRIM33-NTRK1 fusion: ZSWIM5-TP53BP2, TAF4B-WDR1, ABI2-MTA3, and ARID1B-PSMA1. Apart from confirming the presence of RET/PTC1 and RET/PTC3 in positive control samples, we also detected known oncogenic fusion transcripts in remaining samples: TFG-NTRK1, ETV6-NTRK3, MKRN1-BRAF, EML4-ALK, and novel isoform of CCDC6-RET.
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http://dx.doi.org/10.1002/gcc.22737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594006PMC
August 2019

Coexistence of Promoter Mutations and the V600E Alteration and Its Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected Series of Polish Patients.

Int J Mol Sci 2018 Sep 6;19(9). Epub 2018 Sep 6.

Department of Oncological and Reconstructive Surgery, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

promoter (p) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of p mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the V600E mutation. A total of 189 consecutive PTC specimens with known mutational status were evaluated. p mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional p alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the p hotspot mutations were highly correlated with the presence of the V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of p mutations being key molecular modulators responsible for PTC aggressiveness requires further studies.
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http://dx.doi.org/10.3390/ijms19092647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163174PMC
September 2018

131-I MIBG therapy of malignant pheochromocytoma and paraganglioma tumours - a single-centre study.

Endokrynol Pol 2018 12;69(3):246-251. Epub 2018 Apr 12.

Department of Nuclear Medicine and Endocrine Oncology,, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeża Armii Krajowej 15, 44-101 Gliwice, Poland.

Introduction: Pheochromocytomas and paragangliomas are rare tumors deriving from chromaffin cells of adrenal medulla or paraganglia. They are usually benign but 10-35% of them present malignant behavior. The aim of the study was to evaluate the efficacy and safety of 131-I MIBG therapy in malignant pheochromocytoma /paraganglioma patients (MPPGL).

Material And Methods: 18 patients (7 women and 11 men) were included in this study. Between 2002 and 2016 they underwent 131-I MIBG therapy because of MPPGL and their medical data were analyzed retrospectively. Clinical indications for the treatment included progressive disease or massive tissue involvement independently from disease progression. Tumor response for the first time was assessed 3 months after the last treatment according to Response Evaluation Criteria in Solid Tumors criteria and by 131-I MIBG scans.

Results: The mean single dose used was 7.25 GBq (196 mCi) and mean cumulative dose 33.08 GBq ( 894 mCi). In 2 (11%) patients complete tumor response was achieved. In 1 (6%) patient partial response was obtained. In 13 (72%) patients stable disease was observed. In 2 (11%) patients progression was diagnosed three months after treatment discontinuation. In the whole studied group the progression free survival time was 85 months and overall 5-year survival was 87%.

Conclusions: Radionuclide treatment with use of 131-I MIBG may be effective form of palliative treatment for patients with inoperative neoplasm spread, progressive disease or patients requiring alleviation of symptoms. < p > < /p >.
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http://dx.doi.org/10.5603/EP.a2018.0024DOI Listing
October 2018

Discrimination of papillary thyroid cancer from non-cancerous thyroid tissue based on lipid profiling by mass spectrometry imaging.

Endokrynol Pol 2018 ;69(1):2-8

Introduction: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical man-agement. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies. In this study we used mass spectrometry imaging to detect lipids discriminating papillary cancer from not cancerous thyroid directly in formalin-fixed tissue sections.

Material And Methods: For this purpose imaging and profiling of lipids present in non-malignant and cancerous thyroid tissue specimens were conducted. High resolution MALDI-Q-Ion Mobility-TOF-MS technique was used for lipidomic analysis of formalin fixed thyroid tissue samples. Lipids were identified by the comparison of the exact molecular masses and fragmentation pathways of the protonated molecule ions, recorded during the MS/MS experiments, with LIPID MAPS database.

Results: Several phosphatidylcholines (32:0, 32:1, 34:1 and 36:3), sphingomyelins (34:1 and 36:1) and phosphatidic acids (36:2 and 36:3) were detected and their abundances were significantly higher in cancerous tissue compared to non-cancerous tissue. The same lipid species were detected in formalin-fixed as in fresh-frozen tissue, but [M + Na]+ ions were the most abundant in formalin fixed whereas [M + K]+ ions were predominant in fresh tissue.

Conclusions: Our results prove the viability of MALDI-MSI for analysis of lipid distribution directly in formalin-fixed tissue, and the potential for their use in the classification of thyroid diseases.
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http://dx.doi.org/10.5603/EP.a2018.0003DOI Listing
July 2018

Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma. 2018 Update.

Endokrynol Pol 2018 ;69(1):34-74

Nuclear Medicine and Endocrine Oncology Department; M.Sklodowska-Curie Memorial Institute - Cancer Center, Gliwice Branch, Wybrzeze AK 15, 44-100 Gliwice, Poland; Zakład Medycyny Nuklearnej i Endokrynologii Onkologicznej, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Wybrzeże AK 15, 44-100 Gliwice, Poland.

Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines "Diagnostics and Treatment of Thyroid Carcinoma" have been formulated at the "Thyroid Cancer and Other Malignancies of Endocrine Glands" conference held in Wisła in November 2015 [1].
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http://dx.doi.org/10.5603/EP.2018.0014DOI Listing
July 2018

Heterogeneity of Thyroid Cancer.

Pathobiology 2018 6;85(1-2):117-129. Epub 2018 Feb 6.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.

There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example. All these factors contribute to the great complexity in the development of a tumour from cancer cells. In the present review, we summarise the knowledge accumulated about the heterogeneity of TCs. Further research in this direction should help to gain a better understanding of the underlying mechanisms contributing to the development and diversity of TCs, paving the way toward more effective treatment strategies.
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http://dx.doi.org/10.1159/000486422DOI Listing
October 2018

Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?

Int J Mol Sci 2017 Aug 22;18(8). Epub 2017 Aug 22.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Institute-Cancer Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are some aggressive forms, which do not respond to standard treatment. There are still some questions, which have to be resolved to avoid dangerous simplifications in the clinical management. In this article, we focused on the current advantages in preoperative molecular diagnostic tests and histopathological examination including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We discussed the controversies regarding the extent of thyroid surgery and adjuvant radioiodine therapy, as well as new treatment modalities for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Considering medullary thyroid cancer (MTC), we analyzed a clinical management based on histopathology and (ret proto-oncogene) mutation genotype, disease follow-up with a special attention to serum calcitonin doubling time as an important prognostic marker, and targeted therapy applied in advanced MTC. In addition, we provided some data regarding anaplastic thyroid cancer (ATC), a highly lethal neoplasm, which lead to death in nearly 100% of patients due to the lack of effective treatment options.
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http://dx.doi.org/10.3390/ijms18081817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578203PMC
August 2017

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours.

Int J Mol Sci 2017 Jun 2;18(6). Epub 2017 Jun 2.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute-Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (, , , , , , and ). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (, , , ). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.
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http://dx.doi.org/10.3390/ijms18061184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486007PMC
June 2017

Differences in the transcriptome of medullary thyroid cancer regarding the status and type of RET gene mutations.

Sci Rep 2017 02 9;7:42074. Epub 2017 Feb 9.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.

Medullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs as a sporadic form. It is well known that RET mutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type of RET gene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of the RET gene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.
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http://dx.doi.org/10.1038/srep42074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299608PMC
February 2017

Ratio of proliferation markers and HSP90 gene expression as a predictor of pathological complete response in breast cancer neoadjuvant chemotherapy.

Folia Histochem Cytobiol 2016 4;54(4):202-209. Epub 2017 Jan 4.

3rd Department of Radiotherapy and Chemotherapy, Breast Cancer Center, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.

Introduction: Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer. The aim of this study was to validate the utility of proliferation based markers (MKI67 and CDK1) and heat shock proteins (namely HSP90) to predict response to chemotherapy in cohort of breast cancer patients treated preoperatively.

Material And Methods: Ninety-three patients with breast cancer, all females, mean age 42.2 years, among them 32% T1-T2 patients, 49% T3 patients and 13% with T4 tumor stage, 27% N0, 42% N1, 16% N2, 15% N3 were subjected to initial chemotherapy. The majority of patients (86%) received anthracycline and taxane chemotherapy. Among the patients there were 9 individuals with metastatic disease (M1) at initial presentation, and 11 patients were not treated surgically after initial chemotherapy (no sufficient disease response). From 82 patients operated on, 20 patients (24%) showed pathological complete response (pCR), while in 62 patients there was no pCR. 42% of patients were hormone-sensitive HER2-negative, 20% hormone-sensitive HER2-positive, 9% only HER-positive and 29% with triple negative breast cancer. Four gene transcripts (MKI67, cyclin-dependent kinase 1 [CDK1], heat shock proteins HSP90AA1 and HSP- 90AB1) were analyzed in total RNA isolated from single core obtained during preoperative core needle biopsy by quantitative real-time PCR with fluorescent probes (Universal Probe Library, Roche). Results were normalized to the panel of reference genes.

Results: There were no statistically significant differences in MKI67 and CDK1 expression between pCR and no pCR groups (p = 0.099 and 0.35, respectively), although the median expression of both genes was slightly higher in pCR group. In contrast, both HSP90AA1 and HSP90AB1 transcripts showed decreased expression in pCR group (medians 0.77 and 0.55) when compared to no p CR group (median 0.86 and 0.73), statistically significant for HSP90AA1 (p = 0.031) and of borderline significance for HSP90AB1 (p = 0.054). The most significant predictor of pCR was the ratio of CDK1 transcript to HSP90AA transcript. This ratio was significantly higher in CR group (median 0.99) than in no CR group (median 0.68, p = 0.0023), and showed a potential diagnostic utility (area under receiver operating characteristic [ROC] curve 0.72).

Conclusions: HSP90AA1 and AB1 genes exhibit low expression in breast cancers highly sensitive to chemotherapy and may indicate the patients with higher probability of pathological complete response. The ratio of HSP90AA1 to proliferation-related markers (CDK1 or MKI67) may be even better predictor of pCR chance, with higher expression of proliferation genes and lower stress response in patients sensitive to chemotherapy.
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http://dx.doi.org/10.5603/FHC.a2016.0026DOI Listing
March 2017

mutation in prognostication of papillary thyroid cancer (PTC) recurrence.

Gland Surg 2016 Oct;5(5):495-505

Department of Endocrine Surgery, Third Chair of General Surgery, Jagiellonian University, Medical College, Kraków, Poland.

Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinico-pathological risk factors were reported but with controversial conclusions. The prognostic significance of mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30-80%). At present it seems that mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors. The most recent ATA recommendations do not indicate a routine application of status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering and/or status. At present, researchers are working on determining the role of mutation in patients from a low-risk group and its correlations with others molecular events. Currently, mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and therapeutic strategy for PTC patients.
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http://dx.doi.org/10.21037/gs.2016.09.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106385PMC
October 2016

Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast Cancer.

Clin Breast Cancer 2017 Apr 8;17(2):e65-e75. Epub 2016 Sep 8.

Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.

Background: Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches.

Patients And Methods: Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes. Expression of mRNA was correlated with the occurrence of symptomatic BM.

Results: In cohort A, the difference at the noncorrected P < .005 was found for 64 transcripts (P = .23 for global test), but none showed significant difference at a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the largest differences between patients with and without BM in cohort A, none was significantly associated with BM in cohort B.

Conclusion: Analysis based on the primary tumor gene transcripts alone is unlikely to predict BM development in advanced TNBC. Despite its negative findings, the study adds to the knowledge on the biology of TNBC and paves the way for future projects using more advanced molecular assays.
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http://dx.doi.org/10.1016/j.clbc.2016.08.008DOI Listing
April 2017

Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.

Mol Cell Endocrinol 2016 09 6;433:130-7. Epub 2016 Jun 6.

Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland; Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address:

The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity.
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http://dx.doi.org/10.1016/j.mce.2016.06.007DOI Listing
September 2016

Occurrence of phaeochromocytoma tumours in RET mutation carriers - a single-centre study.

Endokrynol Pol 2016 ;67(1):54-8

Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch.

Introduction: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant genetic syndrome caused by germline mutation in RET proto-oncogene. The most common mutations are in a cysteine rich domain. Phaeochromocytoma will develop in approximately 50% of RET proto-oncogene carriers.

Material And Methods: The studied population consisted of 228 RET proto-oncogene mutation carriers. Monitoring for the diagnosis of phaeochromocytoma was carried out in all patients with established genetic status. Mean time of follow up was 138 months. Surveillance consisted of periodically performed clinical evaluation, 24-hour urinary determinations of total metanephrines complementary with imaging (CT, MR, MIBG scintigraphy).

Results: Phaeochromocytoma developed in 41 patients (18% of all RET proto-oncogene mutations carriers). The mean age of diagnosis for the whole cohort was 43 years. In eight cases phaeochromocytoma was the first manifestation of the MEN 2 syndrome. Only eight (20%) patients were symptomatic at diagnosis of phaeochromocytoma. The mean size of the tumour was 4.3 cm. There was no extra-adrenal localisation. We observed one case of malignant phaeochromocytoma.

Conclusions: In patients with MEN 2 syndrome phaeochromocytomas are usually benign adrenal tumours with high risk of bilateral development. Taking to account the latter risk and non-specific clinical manifestation of the neoplasm it is mandatory to screen all RET proto-oncogene mutations carriers for phaeochromocytoma.
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http://dx.doi.org/10.5603/EP.2016.0008DOI Listing
February 2017

Gene signature of the post-Chernobyl papillary thyroid cancer.

Eur J Nucl Med Mol Imaging 2016 Jul 26;43(7):1267-77. Epub 2016 Jan 26.

Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.

Purpose: Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC.

Methods: We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized.

Results: There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples.

Conclusion: Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.
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http://dx.doi.org/10.1007/s00259-015-3303-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869750PMC
July 2016
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