@article{MTMT:34763500, title = {Research autopsy programmes in oncology. shared experience from 14 centres across the world}, url = {https://m2.mtmt.hu/api/publication/34763500}, author = {Geukens, Tatjana and Maetens, Marion and Hooper, Jody E and Oesterreich, Steffi and Lee, Adrian V and Miller, Lori and Atkinson, Jenny M and Rosenzweig, Margaret and Puhalla, Shannon and Thorne, Heather and Devereux, Lisa and Bowtell, David and Loi, Sherene and Bacon, Eliza R and Ihle, Kena and Song, Mihae and Rodriguez-Rodriguez, Lorna and Welm, Alana L and Gauchay, Lisa and Murali, Rajmohan and Chanda, Pharto and Karacay, Ali and Naceur-Lombardelli, Cristina and Bridger, Hayley and Swanton, Charles and Jamal-Hanjani, Mariam and Kollath, Lori and True, Lawrence and Morrissey, Colm and Chambers, Meagan and Chinnaiyan, Arul M and Wilson, Allecia and Mehra, Rohit and Reichert, Zachery and Carey, Lisa A and Perou, Charles M and Kelly, Erin and Maeda, Daichi and Goto, Akiteru and Kulka, Janina and Székely, Borbála and Szász, Attila Marcell and Tőkés, Anna-Mária and Van Den Bogaert, Wouter and Floris, Giuseppe and Desmedt, Christine}, doi = {10.1002/path.6271}, journal-iso = {J PATHOL}, journal = {JOURNAL OF PATHOLOGY}, volume = {Mar 29}, unique-id = {34763500}, issn = {0022-3417}, abstract = {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.}, keywords = {liquid biopsy; metastatic cancer; tissue donation; research autopsy; tumour model}, year = {2024}, eissn = {1096-9896}, orcid-numbers = {Kulka, Janina/0000-0001-6498-5943; Szász, Attila Marcell/0000-0003-2739-4196; Tőkés, Anna-Mária/0000-0002-9581-7536} } @article{MTMT:34343853, title = {Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing}, url = {https://m2.mtmt.hu/api/publication/34343853}, author = {Sztankovics, Dániel and Krencz, Ildikó and Moldvai, Dorottya and Dankó, Titanilla and Nagy, Ákos and Nagy, Noémi and Bedics, Gábor and Rókusz, András and Papp, Gergő and Tőkés, Anna-Mária and Pápay, Judit and Sápi, Zoltán and Dezső, Katalin and Bödör, Csaba and Sebestyén, Anna}, doi = {10.1038/s41598-023-46927-x}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34343853}, issn = {2045-2322}, abstract = {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.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Krencz, Ildikó/0000-0003-3601-8723; Dankó, Titanilla/0000-0002-7419-4560; Bedics, Gábor/0000-0003-4628-2384; Papp, Gergő/0000-0001-5840-2369; Tőkés, Anna-Mária/0000-0002-9581-7536; Pápay, Judit/0000-0003-2642-2060; Dezső, Katalin/0000-0002-4856-0483; Bödör, Csaba/0000-0002-0729-692X; Sebestyén, Anna/0000-0001-8814-4794} } @article{MTMT:34128119, title = {Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins, superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions}, url = {https://m2.mtmt.hu/api/publication/34128119}, author = {Kugler, Szilvia and Tőkés, Anna-Mária and Nagy, Nándor and Fintha, Attila and Danics, Krisztina and Sághi, Márton and Törő, Klára Andrea and Rácz, Gergely and Nemeskéri, Ágnes}, doi = {10.1111/joa.13947}, journal-iso = {J ANAT}, journal = {JOURNAL OF ANATOMY}, volume = {2023}, unique-id = {34128119}, issn = {0021-8782}, year = {2023}, eissn = {1469-7580}, orcid-numbers = {Tőkés, Anna-Mária/0000-0002-9581-7536; Nagy, Nándor/0000-0002-6223-5214; Fintha, Attila/0000-0002-0519-8170; Danics, Krisztina/0000-0002-3694-5706; Törő, Klára Andrea/0000-0002-0254-1439} } @article{MTMT:34112970, title = {The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience}, url = {https://m2.mtmt.hu/api/publication/34112970}, author = {Dank, Magdolna and Mühl, Dorottya and Pölhös, Annamária and Csanda, Renata and Herold, Magdolna and Kovács, Attila and Madaras, Lilla and Kulka, Janina and Pálházy, Tímea and Tőkés, Anna-Mária and Tóth, Mónika Anna and Újhelyi, Mihály and Szász, Attila Marcell and Herold, Zoltán}, doi = {10.3390/genes14091708}, journal-iso = {GENES-BASEL}, journal = {GENES}, volume = {14}, unique-id = {34112970}, issn = {2073-4425}, year = {2023}, eissn = {2073-4425}, orcid-numbers = {Dank, Magdolna/0000-0002-4442-8733; Mühl, Dorottya/0000-0001-7565-8462; Herold, Magdolna/0000-0002-1036-6343; Madaras, Lilla/0000-0002-4137-4696; Kulka, Janina/0000-0001-6498-5943; Pálházy, Tímea/0000-0002-0542-8976; Tőkés, Anna-Mária/0000-0002-9581-7536; Szász, Attila Marcell/0000-0003-2739-4196; Herold, Zoltán/0000-0001-5990-4889} } @article{MTMT:33846881, title = {Tumour-stroma ratio (TSR) in breast cancer: comparison of scoring core biopsies versus resection specimens}, url = {https://m2.mtmt.hu/api/publication/33846881}, author = {Karancsi, Zsófia and Hagenaars, Sophie C. and Németh , Kristóf and Mesker, Wilma E. and Tőkés, Anna-Mária and Kulka, Janina}, doi = {10.1007/s00428-023-03555-0}, journal-iso = {VIRCHOWS ARCH}, journal = {VIRCHOWS ARCHIV}, volume = {In press}, unique-id = {33846881}, issn = {0945-6317}, year = {2023}, eissn = {1432-2307}, orcid-numbers = {Tőkés, Anna-Mária/0000-0002-9581-7536; Kulka, Janina/0000-0001-6498-5943} } @article{MTMT:33814839, title = {Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort}, url = {https://m2.mtmt.hu/api/publication/33814839}, author = {Pipek, Orsolya Anna and Alpár, Donát and Rusz, Orsolya and Bödör, Csaba and Udvarnoki, Zoltán András and Medgyes-Horváth, Anna and Csabai, István and Szállási, Zoltán and Madaras, Lilla and Kahán, Zsuzsanna and Cserni, Gábor and Kővári, Bence and Kulka, Janina and Tőkés, Anna-Mária}, doi = {10.3390/ijms24108553}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33814839}, issn = {1661-6596}, abstract = {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.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Pipek, Orsolya Anna/0000-0001-8109-0340; Rusz, Orsolya/0000-0001-5726-4072; Bödör, Csaba/0000-0002-0729-692X; Udvarnoki, Zoltán András/0000-0001-7086-235X; Medgyes-Horváth, Anna/0000-0003-4435-5797; Csabai, István/0000-0001-9232-9898; Szállási, Zoltán/0000-0001-5395-7509; Madaras, Lilla/0000-0002-4137-4696; Kahán, Zsuzsanna/0000-0002-5021-8775; Cserni, Gábor/0000-0003-1344-7744; Kővári, Bence/0000-0002-4498-8781; Kulka, Janina/0000-0001-6498-5943; Tőkés, Anna-Mária/0000-0002-9581-7536} } @article{MTMT:33174753, title = {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}, url = {https://m2.mtmt.hu/api/publication/33174753}, author = {Veres, Amarilla and Tőkés, Anna-Mária and Tóth, Jeannette and Szilágyi, Zsuzsa and Tóth, Éva Katalin and Nagy, Zoltán Zsolt and Horváth, Anna}, doi = {10.1159/000524176}, journal-iso = {CASE REP ONCOL}, journal = {CASE REPORTS IN ONCOLOGY}, volume = {15}, unique-id = {33174753}, abstract = {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.}, keywords = {DYSFUNCTION; EXPRESSION; meibomian gland dysfunction; Her2+breast cancer; Anti-HER2 biological therapy anastrozole}, year = {2022}, eissn = {1662-6575}, pages = {486-493}, orcid-numbers = {Veres, Amarilla/0000-0002-6671-233X; Tőkés, Anna-Mária/0000-0002-9581-7536; Tóth, Éva Katalin/0000-0001-9960-9833; Nagy, Zoltán Zsolt/0000-0002-7330-0464; Horváth, Anna/0000-0003-3229-5643} } @article{MTMT:33128050, title = {Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis}, url = {https://m2.mtmt.hu/api/publication/33128050}, author = {Bakos, Éva and Nemet, Orsolya and Kucsma, Nóra and Tökési, Natália and Stieger, Bruno and Rushing, Elisabeth and Tőkés, Anna-Mária and Kele, Péter and Tusnády, Gábor and Laczka, Csilla}, doi = {10.3389/fphar.2022.958023}, journal-iso = {FRONT PHARMACOL}, journal = {FRONTIERS IN PHARMACOLOGY}, volume = {13}, unique-id = {33128050}, abstract = {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.}, keywords = {PEPTIDES; LOCALIZATION; IDENTIFICATION; MESSENGER-RNA; MEDIATED TRANSPORT; PANCREATIC-CANCER; Isoform; Choroid Plexus; testis; steroid transport; OATP2B1; organic anion transporting polypeptide (OATP); 1B3}, year = {2022}, eissn = {1663-9812}, orcid-numbers = {Tőkés, Anna-Mária/0000-0002-9581-7536} } @article{MTMT:32804574, title = {Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas}, url = {https://m2.mtmt.hu/api/publication/32804574}, author = {Tőkés, Anna-Mária and Vári-Kakas, S. and Kulka, Janina and Törőcsik, Beáta}, doi = {10.3389/fonc.2022.850401}, journal-iso = {FRONT ONCOL}, journal = {FRONTIERS IN ONCOLOGY}, volume = {12}, unique-id = {32804574}, issn = {2234-943X}, year = {2022}, eissn = {2234-943X}, orcid-numbers = {Tőkés, Anna-Mária/0000-0002-9581-7536; Kulka, Janina/0000-0001-6498-5943; Törőcsik, Beáta/0000-0002-9838-3710} } @article{MTMT:32793328, title = {Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes}, url = {https://m2.mtmt.hu/api/publication/32793328}, author = {Szeitz, Beáta and Pipek, Orsolya Anna and Kulka, Janina and Szundi, Csilla and Rusz, Orsolya and Tőkés, Tímea and Szász, Attila Marcell and Kovács, Attila and Pesti, Adrián István and Ben Arie, Taya Beri and Gángó, Ambrus and Fülöp, Zsolt and Drágus, Emőke and Vári-Kakas, Stefan A. and Tőkés, Anna-Mária}, doi = {10.3390/cancers14081942}, journal-iso = {CANCERS}, journal = {CANCERS}, volume = {14}, unique-id = {32793328}, year = {2022}, eissn = {2072-6694}, orcid-numbers = {Szeitz, Beáta/0000-0001-6414-0537; Pipek, Orsolya Anna/0000-0001-8109-0340; Kulka, Janina/0000-0001-6498-5943; Rusz, Orsolya/0000-0001-5726-4072; Tőkés, Tímea/0000-0002-5456-1706; Szász, Attila Marcell/0000-0003-2739-4196; Pesti, Adrián István/0000-0001-6706-6221; Gángó, Ambrus/0000-0001-9127-5015; Fülöp, Zsolt/0000-0002-0854-5617; Tőkés, Anna-Mária/0000-0002-9581-7536} }