TY - JOUR AU - Geukens, Tatjana AU - Maetens, Marion AU - Hooper, Jody E AU - Oesterreich, Steffi AU - Lee, Adrian V AU - Miller, Lori AU - Atkinson, Jenny M AU - Rosenzweig, Margaret AU - Puhalla, Shannon AU - Thorne, Heather AU - Devereux, Lisa AU - Bowtell, David AU - Loi, Sherene AU - Bacon, Eliza R AU - Ihle, Kena AU - Song, Mihae AU - Rodriguez-Rodriguez, Lorna AU - Welm, Alana L AU - Gauchay, Lisa AU - Murali, Rajmohan AU - Chanda, Pharto AU - Karacay, Ali AU - Naceur-Lombardelli, Cristina AU - Bridger, Hayley AU - Swanton, Charles AU - Jamal-Hanjani, Mariam AU - Kollath, Lori AU - True, Lawrence AU - Morrissey, Colm AU - Chambers, Meagan AU - Chinnaiyan, Arul M AU - Wilson, Allecia AU - Mehra, Rohit AU - Reichert, Zachery AU - Carey, Lisa A AU - Perou, Charles M AU - Kelly, Erin AU - Maeda, Daichi AU - Goto, Akiteru AU - Kulka, Janina AU - Székely, Borbála AU - Szász, Attila Marcell AU - Tőkés, Anna-Mária AU - Van Den Bogaert, Wouter AU - Floris, Giuseppe AU - Desmedt, Christine TI - Research autopsy programmes in oncology. shared experience from 14 centres across the world TS - shared experience from 14 centres across the world JF - JOURNAL OF PATHOLOGY J2 - J PATHOL VL - Mar 29 PY - 2024 SN - 0022-3417 DO - 10.1002/path.6271 UR - https://m2.mtmt.hu/api/publication/34763500 ID - 34763500 AB - While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide. Fourteen programmes participated in this study. Eight programmes operated 24 h/7 days, resulting in a lower median postmortem interval (time between death and start of the autopsy, 4 h) compared with those operating during working hours (9 h). Most programmes (n = 10) succeeded in collecting all samples within a median of 12 h after death. A large number of tumour sites were sampled during each autopsy (median 15.5 per patient). The median number of samples collected per patient was 58, including different processing methods for tumour samples but also non-tumour tissues and liquid biopsies. Unique biological insights derived from these samples included metastatic progression, treatment resistance, disease heterogeneity, tumour dormancy, interactions with the tumour micro-environment, and tumour representation in liquid biopsies. Tumour patient-derived xenograft (PDX) or organoid (PDO) models were additionally established, allowing for drug discovery and treatment sensitivity assays. Apart from the opportunities and achievements, we also present the challenges related with postmortem sample collections and strategies to overcome them, based on the shared experience of these 14 programmes. Through this work, we hope to increase the transparency of postmortem tissue donation, to encourage and aid the creation of new programmes, and to foster collaborations on these unique sample collections. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. LA - English DB - MTMT ER - TY - JOUR AU - Sztankovics, Dániel AU - Krencz, Ildikó AU - Moldvai, Dorottya AU - Dankó, Titanilla AU - Nagy, Ákos AU - Nagy, Noémi AU - Bedics, Gábor AU - Rókusz, András AU - Papp, Gergő AU - Tőkés, Anna-Mária AU - Pápay, Judit AU - Sápi, Zoltán AU - Dezső, Katalin AU - Bödör, Csaba AU - Sebestyén, Anna TI - Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 12 SN - 2045-2322 DO - 10.1038/s41598-023-46927-x UR - https://m2.mtmt.hu/api/publication/34343853 ID - 34343853 AB - Alterations in mTOR signalling molecules, including RICTOR amplification, have been previously described in many cancers, particularly associated with poor prognosis. In this study, RICTOR copy number variation (CNV) results of diagnostic next-generation sequencing (NGS) were analysed in 420 various human malignant tissues. RICTOR amplification was tested by Droplet Digital PCR (ddPCR) and validated using the “gold standard” fluorescence in situ hybridisation (FISH). Additionally, the consequences of Rictor protein expression were also studied by immunohistochemistry. RICTOR amplification was presumed in 37 cases with CNV ≥ 3 by NGS, among these, 16 cases (16/420; 3.8%) could be validated by FISH, however, ddPCR confirmed only 11 RICTOR -amplified cases with lower sensitivity. Based on these, neither NGS nor ddPCR could replace traditional FISH in proof of RICTOR amplification. However, NGS could be beneficial to highlight potential RICTOR -amplified cases. The obtained results of the 14 different tumour types with FISH-validated RICTOR amplification demonstrate the importance of RICTOR amplification in a broad spectrum of tumours. The newly described RICTOR -amplified entities could initiate further collaborative studies with larger cohorts to analyse the prevalence of RICTOR amplification in rare diseases. Finally, our and further work could help to improve and expand future therapeutic opportunities for mTOR-targeted therapies. LA - English DB - MTMT ER - TY - JOUR AU - Kugler, Szilvia AU - Tőkés, Anna-Mária AU - Nagy, Nándor AU - Fintha, Attila AU - Danics, Krisztina AU - Sághi, Márton AU - Törő, Klára Andrea AU - Rácz, Gergely AU - Nemeskéri, Ágnes TI - Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins, superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions JF - JOURNAL OF ANATOMY J2 - J ANAT VL - 2023 PY - 2023 PG - 13 SN - 0021-8782 DO - 10.1111/joa.13947 UR - https://m2.mtmt.hu/api/publication/34128119 ID - 34128119 N1 - Funding Agency and Grant Number: Hungarian Science Foundation NKFI grant [138664]; Istvan Apathy Foundation's Research Grant; Research Excellence Programme of the Ministry for Innovation and Technology in Hungary thematic programme of the Semmelweis University [TKP2021-EGA- 25] Funding text: Hungarian Science Foundation NKFI grant, Grant/Award Number: 138664; Istvan Apathy Foundation's Research Grant; Research Excellence Programme of the Ministry for Innovation and Technology in Hungary, TKP2021-EGA- 25 thematic programme of the Semmelweis University LA - English DB - MTMT ER - TY - JOUR AU - Dank, Magdolna AU - Mühl, Dorottya AU - Pölhös, Annamária AU - Csanda, Renata AU - Herold, Magdolna AU - Kovács, Attila AU - Madaras, Lilla AU - Kulka, Janina AU - Pálházy, Tímea AU - Tőkés, Anna-Mária AU - Tóth, Mónika Anna AU - Újhelyi, Mihály AU - Szász, Attila Marcell AU - Herold, Zoltán TI - The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience JF - GENES J2 - GENES-BASEL VL - 14 PY - 2023 IS - 9 PG - 14 SN - 2073-4425 DO - 10.3390/genes14091708 UR - https://m2.mtmt.hu/api/publication/34112970 ID - 34112970 N1 - Export Date: 15 December 2023 LA - English DB - MTMT ER - TY - JOUR AU - Karancsi, Zsófia AU - Hagenaars, Sophie C. AU - Németh , Kristóf AU - Mesker, Wilma E. AU - Tőkés, Anna-Mária AU - Kulka, Janina TI - Tumour-stroma ratio (TSR) in breast cancer: comparison of scoring core biopsies versus resection specimens JF - VIRCHOWS ARCHIV J2 - VIRCHOWS ARCH VL - In press PY - 2023 PG - 14 SN - 0945-6317 DO - 10.1007/s00428-023-03555-0 UR - https://m2.mtmt.hu/api/publication/33846881 ID - 33846881 LA - English DB - MTMT ER - TY - JOUR AU - Pipek, Orsolya Anna AU - Alpár, Donát AU - Rusz, Orsolya AU - Bödör, Csaba AU - Udvarnoki, Zoltán András AU - Medgyes-Horváth, Anna AU - Csabai, István AU - Szállási, Zoltán AU - Madaras, Lilla AU - Kahán, Zsuzsanna AU - Cserni, Gábor AU - Kővári, Bence AU - Kulka, Janina AU - Tőkés, Anna-Mária TI - Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 10 PG - 19 SN - 1661-6596 DO - 10.3390/ijms24108553 UR - https://m2.mtmt.hu/api/publication/33814839 ID - 33814839 N1 - Funding Agency and Grant Number: NKFIH, Hungary [FK20-134253, K21-137948, TKP2021-EGA-24, TKP2021-NVA-15, NVKP-16-1-2016-0004]; EU's Horizon 2020 research and innovation program [739593]; Janos Bolyai Research Scholarship program of the Hungarian Academy of Sciences [BO/00125/22]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-22-5-SE-7]; Complementary Research Excellence Program; Kerpel Talent Award of Semmelweis University [EFOP-3.6.3-VEKOP-16-2017-00009]; ELIXIR Hungary Funding text: This study was supported by the following grants: NKFIH, Hungary: FK20-134253, K21-137948, TKP2021-EGA-24, TKP2021-NVA-15 and NVKP-16-1-2016-0004. The study was also supported by the EU's Horizon 2020 research and innovation program (No. 739593), the Janos Bolyai Research Scholarship program (BO/00125/22) of the Hungarian Academy of Sciences, the UNKP-22-5-SE-7 grant of the New National Excellence Program of the Ministry for Innovation and Technology, by the Complementary Research Excellence Program, the Kerpel Talent Award of Semmelweis University (EFOP-3.6.3-VEKOP-16-2017-00009), and the ELIXIR Hungary. AB - A limited number of studies have focused on the mutational landscape of breast cancer in different ethnic populations within Europe and compared the data with other ethnic groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian breast cancer patients. We validated a subset of the identified variants at the DNA level using the Illumina TruSight Oncology (TSO) 500 assay. Canonical breast-cancer-associated genes with pathogenic germline mutations were CHEK2 and ATM. Nearly all the observed germline mutations were as frequent in the Hungarian breast cancer cohort as in independent European populations. The majority of the detected somatic short variants were single-nucleotide polymorphisms (SNPs), and only 8% and 6% of them were deletions or insertions, respectively. The genes most frequently affected by somatic mutations were KMT2C (31%), MUC4 (34%), PIK3CA (18%), and TP53 (34%). Copy number alterations were most common in the NBN, RAD51C, BRIP1, and CDH1 genes. For many samples, the somatic mutational landscape was dominated by mutational processes associated with homologous recombination deficiency (HRD). Our study, as the first breast tumor/normal sequencing study in Hungary, revealed several aspects of the significantly mutated genes and mutational signatures, and some of the copy number variations and somatic fusion events. Multiple signs of HRD were detected, highlighting the value of the comprehensive genomic characterization of breast cancer patient populations. LA - English DB - MTMT ER - TY - JOUR AU - Veres, Amarilla AU - Tőkés, Anna-Mária AU - Tóth, Jeannette AU - Szilágyi, Zsuzsa AU - Tóth, Éva Katalin AU - Nagy, Zoltán Zsolt AU - Horváth, Anna TI - Novel Meibomian Gland and Tarsal Conjunctival Changes Associated with Trastuzumab, Pertuzumab, and Anastrozole Treatment for Metastatic HER2 Positive Breast Cancer: A Case Report and Literature Review JF - CASE REPORTS IN ONCOLOGY J2 - CASE REP ONCOL VL - 15 PY - 2022 IS - 2 SP - 486 EP - 493 PG - 8 SN - 1662-6575 DO - 10.1159/000524176 UR - https://m2.mtmt.hu/api/publication/33174753 ID - 33174753 AB - The aim of the study was to report a case of severe meibomian gland dysfunction (MGD) and conjunctival changes associated with trastuzumab, pertuzumab, and anastrozole therapy in a HER-2 positive breast cancer patient. A 57-year-old white woman was treated with trastuzumab and pertuzumab biological and anastrozole endocrine therapy for metastatic breast cancer for several months. She suffered from intense eye pain and foreign body sensation. On the ocular surface, severe MGD developed without corneal lesions. On the tarsal conjunctiva, circumscribed lesions evolved 6 months after receiving anticancer therapy. After biopsy, the histological assessment excluded metastasis or chalazion. The lesion consisted of subepithelial lymphocytic infiltrates surrounding lipid-laden CD68-positive macrophages. Besides the redundant lipid accumulation, no acute necrotic reaction was seen. Noncontact infrared meibography visualized ductal drop-out in the upper and lower lids, and functional tests confirmed severe MGD. During the 18-month follow-up, the patient received treatment for MGD and no new conjunctival lesions developed, subjective symptoms subsided, and ocular surface morphology remained unchanged. The novel HER2-inhibitor trastuzumab and pertuzumab biological therapy and anastrozole endocrine therapy were associated with the disruption of the ocular surface milieu. The new histological aspect of tarsal conjunctiva changes may give a hint to understand the potential underlying molecular mechanisms of anticancer therapy-associated severe MGD. Since anticancer therapies may substantially interfere with the ocular surface milieu, awareness of this side effect leads to improved care of oncology patients. LA - English DB - MTMT ER - TY - JOUR AU - Bakos, Éva AU - Nemet, Orsolya AU - Kucsma, Nóra AU - Tökési, Natália AU - Stieger, Bruno AU - Rushing, Elisabeth AU - Tőkés, Anna-Mária AU - Kele, Péter AU - Tusnády, Gábor AU - Laczka, Csilla TI - Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 13 PY - 2022 PG - 12 SN - 1663-9812 DO - 10.3389/fphar.2022.958023 UR - https://m2.mtmt.hu/api/publication/33128050 ID - 33128050 AB - Organic anion transporting polypeptide 3A1 (OATP3A1, encoded by the SLCO3A1 gene) is a prostaglandin, oligopeptide, and steroid/thyroid hormone transporter with wide tissue distribution, expressed, e.g., in the human brain and testis. Although the physiological importance of OATP3A1 has not yet been clarified, based on its expression pattern, substrate recognition, and evolutionary conservation, OATP3A1 is a potential pharmacological target. Previously, two isoforms of OATP3A1, termed as V1 and V2, have been characterized. Here, we describe the cloning and functional characterization of a third isoform, OATP3A1_V3. The mRNA of isoform V3 is formed by alternative splicing and results in an OATP3A1 protein with an altered C-terminus compared to isoforms V1 and V2. Based on quantitative PCR, we demonstrate the widespread expression of SLCO3A1_V3 mRNA in human organs, with the highest expression in the brain and testis. By generation of an isoform V3-specific antibody and immunostaining, we show that the encoded protein is expressed in the human choroid plexus, neurons, and both germ and Sertoli cells of the testis. Moreover, we demonstrate that in contrast to isoform V1, OATP3A1_V3 localizes to the apical membrane of polarized MDCKII cells. Using HEK-293 cells engineered to overexpress OATP3A1_V3, we verify the protein's functionality and identify dehydroepiandrosterone sulfate as a novel OATP3A1 substrate. Based on their distinct expression patterns but overlapping functions, OATP3A1 isoforms may contribute to transcellular (neuro)steroid transport in the central nervous system. LA - English DB - MTMT ER - TY - JOUR AU - Tőkés, Anna-Mária AU - Vári-Kakas, S. AU - Kulka, Janina AU - Törőcsik, Beáta TI - Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 12 PY - 2022 PG - 23 SN - 2234-943X DO - 10.3389/fonc.2022.850401 UR - https://m2.mtmt.hu/api/publication/32804574 ID - 32804574 LA - English DB - MTMT ER - TY - JOUR AU - Szeitz, Beáta AU - Pipek, Orsolya Anna AU - Kulka, Janina AU - Szundi, Csilla AU - Rusz, Orsolya AU - Tőkés, Tímea AU - Szász, Attila Marcell AU - Kovács, Attila AU - Pesti, Adrián István AU - Ben Arie, Taya Beri AU - Gángó, Ambrus AU - Fülöp, Zsolt AU - Drágus, Emőke AU - Vári-Kakas, Stefan A. AU - Tőkés, Anna-Mária TI - Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes JF - CANCERS J2 - CANCERS VL - 14 PY - 2022 IS - 8 PG - 22 SN - 2072-6694 DO - 10.3390/cancers14081942 UR - https://m2.mtmt.hu/api/publication/32793328 ID - 32793328 LA - English DB - MTMT ER -