IgA nephropathy (IgAN) represents the most prevalent form of glomerulonephritis globally, posing significant challenges due to its variable clinical course and potential for recurrence post-kidney transplantation. However, the underlying pathophysiology of IgAN recurrence in transplanted kidneys remains poorly understood. Herein, we aimed to investigate the role of heme oxygenase (HO) and hemoglobin V (HgV) staining in the progression of IgAN. Initially twenty-two patients with biopsy-proven IgAN were enrolled and followed from 2013 till 2024 or until the initiation of renal replacement therapy (RRT), renal transplantation, or death. Clinical data, including kidney function, proteinuria, and hematuria, were collected from medical records. Histological classification according to the Oxford criteria and staining for HO and HgV were performed to assess heme oxygenase and hemoglobin V expression. Results revealed that 9 out of 22 patients required RRT, with 6 of them undergoing kidney transplantation. Analysis of HO and HgV staining demonstrated significant alterations associated with disease severity and prognosis. Furthermore, correlations were observed between staining patterns and histological parameters of IgAN. The staining intensity of heme oxygenase (HO) and hemoglobin V (HgV) was correlated with interstitial fibrosis and tubular atrophy (IFTA) based on age, sex, estimated glomerular filtration rate (eGFR), and proteinuria. Our analysis revealed intriguing associations between staining intensity for interstitial fibrosis and tubular atrophy and these demographic and clinical parameters, highlighting potential influences on the pathogenesis and progression of IgA nephropathy. Variations in staining intensity were observed across different age groups, sexes, and levels of eGFR and proteinuria, underscoring the importance of considering individual patient characteristics in the assessment and management of IgA nephropathy. These findings emphasize the need for personalized therapeutic strategies tailored to specific patient profiles, with the potential to improve treatment outcomes and patient care. Further studies focusing on these associations may deepen our understanding of disease mechanisms and inform the development of targeted interventions for patients with IgA nephropathy.

Témavezető: Dr. Bidiga László

Introduction: Diabetic nephropathy (DN) is a one of the most serious complications of DM and leading cause of chronic kidney disease, characterized by progressive glomerular and interstitial damage. Objective: This study investigates cellular and histopathological changes in DN using immunohistochemical markers and correlates these findings with clinical parameters. Kidney biopsies from 14 DN cases and 2 controls were analyzed. These 14DN cases belong to the class 3 and 4 according to the Tervate classification. Method: WT1 immunostaining was used to quantify podocyte loss. Extensive podocyte loss and subsequent repopulation by migrating/proliferating parietal epithelial cell. Proliferating palisading epithelial cell lack of expression of podocyte marker and express markers of proliferation, cell migration, and parietal epithelium. MIB1 staining highlighted mitotic activity in parietal epithelial cells, suggesting potential compensatory mechanisms to cover the bare glomerular basement membrane (GBM). CK18 staining identified retroglomerular migration of tubular epithelial cells at the glomerular apex, further supporting the hypothesis of cellular adaptation to podocyte loss. Hale’s colloidal iron staining (HALE) demonstrated reduced intensity on glomerular capillary tufts in DN cases, correlating with podocyte depletion.CD68-positive macrophages in the interstitium were quantified, showing a correlation between chronic inflammation and the severity of interstitial fibrosis and tubular atrophy (IFTA). The findings were correlated with clinical parameters, including proteinuria and renal function, to explore the relationship between histological alterations and disease progression. Results: In the HALE study, the average control value was 95%, with 50% for class 3 and 22.6% for class 4, suggesting podocyte loss. For WT1, the average intraglomerular cell count in the control group was 49, and in the Bowman's capsule (BC), it was 16. In contrast, DN cases showed an average intraglomerular cell count of 8.5 and an average of 6.2 cells in the BC. MIB1 positivity was observed in 7 out of 14 DN cases, while CK18 was positive in 4 out of 14 DN cases. Regarding CD68, the control group had an average of 13.5, whereas DN cases had an average of 29. Conclusion: This study highlights the interplay between podocyte loss, cellular adaptation, inflammation, and functional decline in DN, providing insights into the pathological mechanisms and potential therapeutic targets.

Témavezető: Dr.Bidiga Laszlo

Cartilage is avascular connective tissue that thrives in a hypoxic microenvironment, where oxygen levels are naturally low. Hypoxia-inducible factors (HIFs) play a pivotal role in chondroprogenitor cell differentiation, thus therapeutic avenues for cartilage disorders like osteoarthritis may be centred on replicating the effects of HIFs. Notably, HIFs modulate the circadian clock, the master regulator, governing a variety of physiological processses within an approximately 24-hour cycle, thereby synchronising secondary oscillators in peripheral tissues such as articulate cartilage. This study employs a hypoxic incubator to establish a controlled low-oxygen environment, offering a physiologically relevant model to study the interaction between hypoxia and circadian clock regulation. Chondroprogenitor cells isolated from the limb buds of 4.5-day-old chicken embryos were used to establish high- density (HD) cultures. Cultures were exposed to hypoxic conditions (1% O2, 10% CO2) during the early stage of in vitro chondrogenesis. Samples were harvested at specific time points representing specific stages of chondrification. Cartilage formation was assessed using dimethyl-methylene blue (DMMB) staining to detect cartilage-specific extracellular matrix formation. Cell viability was assessed using the MTT Assay to confirm hypoxia tolerance. Real- time quantitative polymerase chain reaction (RT-qPCR) was performed to quantify mRNA expression of chondrogenic markers (SOX9, COL2A1, ACAN), circadian clock genes (BMAL1, PER2, CRY1), and one hypoxia responsive gene (HIF-1A). While results of the MTT assay showed that the differentiating cells tolerated the hypoxic treatment well and no significant change was examined, the DMMB stained HD cultures exhibited stronger metachromasia after the treatment, indicating an elevated level of extracellular matrix production. Upon the analysation of the chondrogenic, clock and hypoxia responsive marker genes, unambiguous oscillations were discovered in the expression patterns, meaning that the hypoxic treatment induced the synchronization of the molecular clockwork in the differentiating chondrocytes. We can conclude that the hypoxic environment had a positive effect on in vitro cartilage formation, if it was applied during the early stage of chondrogenesis. Altering the hypoxia-dependent signaling pathways in chondroprogenitor cells may have an important role in the generation of high-quality hyaline cartilage.

Témavezető: Dr. Vágó Judit

Introduction: Chondrogenesis is a multistep process when mesenchymal stem cells differentiate into chondrocytes and produce cartilage specific extracellular matrix under the effect of different stimuli. Caloric restriction, a dietary regimen that reduces energy intake without malnutrition is known for its various health benefits. It enhances proliferation and stem cell renewal, thus it increases the regenerative capacity of various tissues but it has not been extensively studied in the context of chondrogenesis. Based on this theory, the aim of our study was to examine the possible effects of caloric restriction on the chondrogenic differentiation of human mesenchymal stem cells. Methods: High density cell cultures established from immortalized human mesenchymal stem cells (hTERT-hMSC)were cultured in chondrogenic differentiation medium for 20 days under control conditions. Caloric restriction was performed by eliminating glucose from the cell culture medium for 72 hours between day 5 to day 8 or day 10 to day 13. After the 3-day-long fasting, cells received complete differentiation medium containing 1.5 g/L glucose (on Day8 and Day13, respectively). To investigate the influence of caloric restiction samples were collected on day 5, 10, 15 and 20. Cell viability was studied by MTT assay, the extracellular matrix production was examined by metachromatic staining and total RNA was isolated, reverse transcripted and analyzed for the expression of human mesenchmyal stem cell and chondrogenic marker genes using RT-qPCR. Results: Our initial findings reveal that chondrogenic differentiation has been occured in the human mesenchymal micromass cultures and 3- day-long caloric restriction influences that. Cell viability did not show significant changes under the fasting, but alteration of the gene expression of stem cell and chondrogenic markers were observed following glucose elimination. Conclusion: Our results suggest that transient caloric restriction influences in vitro chondrogenesis without significant alteration of cellular viability. Further experiments are needed to elucidate the exact mechanism of these effects.

Témavezető: Katona Éva és Dr. Zákány Róza

Introduction Allogeneic bone marrow transplantation, involving donor stem cell transfer, treats hematological disorders but carries risks like graft-versus-host disease (GVHD) and immunosuppression. In Hungary, autopsies are legally mandated for all such patients, a rare global requirement. This study uniquely explores post-transplant complications, addressing limitations of smaller case reviews, and examines autopsy and clinical reports to identify key complications. Method We analyzed autopsy reports and clinical records of 41 transplant recipients at the University of Debrecen (2016–2023). Data from UDmed and GLIMS included clinical and autopsy records. Multiple clinical parameters were evaluated to identify mortality factors and improve future patient outcomes. Results Of 41 patients, 66% were men, and 64% aged 40–65. Acute Myeloid Leukemia (AML) was most common (48%), followed by Myelodysplastic Syndrome (ALL, 29%) and Acute Lymphoid Leukemia (ALL, 23%). Leading causes of death were septic shock (42%), nosocomial (49%), and opportunistic infections (71%). Graft failure occurred in 49%, thrombotic events in 37%, and acute hemorrhagic events in 51%. GVHD was assessed in 25 patients within 100 days post-transplant. Clinical reports identified GVHD in 2 skin, 6 gastrointestinal, and 6 liver cases, while autopsy reports detected it in 1 skin, 12 gastrointestinal, and 14 liver cases. Clinical criteria generally provided more precise diagnostic insights. The mean time from treatment to death was 134 days (range: 8–962 days). Conclusion Septic shock, graft failure, and acute hemorrhagic and thrombotic events are primary complications post-transplant. Opportunistic and nosocomial infections significantly contribute to mortality. These findings align with limited existing literature, underscoring this study's unique contribution to addressing knowledge gaps.

Témavezető: Dr. Bedekovics Judit

Introduction: Pediatric Central Nervous System (CNS) tumours are the second most frequent malignancies in children, representing a significant health concern due to their complexity and impact on survival rates. The most common tumours are astrocytomas, with the most prevalent subtype being pilocytic astrocytoma (PA)which accounts for approximately 20% of paediatric tumours,it is characterised by slow growth and favourable outcomes.The increasing prevalence of these CNS tumours makes it imperative to have improved classification systems with comprehensive overviews of frequency, characteristics, and emerging trends to have targeted therapies for these tumours. Objective: Statistical analysis of pediatric CNS tumours in University of Debrecen between 2014 and 2024. Examining p16 expression in the most frequent glial paediatric tumours and its association with BRAF status. Method: Statistical evaluation was based on histopathology reports collected from GLIMS database. Formalin fixed paraffin embedded tissue blocks were used from the archive. P16 expression was assessed as a percentage of positive tumour cells and intensity of staining. BRAF status was collected from the pathology reports. Results: The frequency of glial, glioneuronal and neuronal tumours was 0.5586(56%) which translates to 162 out of the 290 samples. The frequency of pilocytic astrocytoma specifically was 0.2621(26%) which translates to 76 out of the 290 patients’ samples. There was a significantly higher p16 expression in gangliogliomas as compared to astrocytomas (p=0.0078, Mann Whitney test), there was significantly higher p16 expression in pilocytic astrocytoma compared to adult diffuse astrocytoma (p=0.0065, Mann Whitney). There was no significant difference between gangliogliomas and pilocytic astrocytoma (p=0.2220, Mann Whitney). The highest intensity was observed in gangliogliomas, which group showed significantly higher intensity comparing to astrocytomas. The p16 expression was independent from the BRAF status. Conclusion: Pilocytic astrocytoma is the most frequent paediatric CNS tumour. It may show morphological overlap with adult glial tumours. P16 expression was significantly higher in PA comparing to adult diffuse astrocytoma. It may be a useful marker in improving diagnostic accuracy and hence targeted therapeutic interventions.

Témavezető: Dr Judit Bedekovics

Carbonic anhydrase IX (CAIX), a hypoxia-induced enzyme, plays a pivotal role in the progression of cancer, such as rectal adenocarcinomas, by modulating the tumor microenvironment. Stromal CAIX, in particular, creates an immune- suppressive microenvironment by limiting lymphocyte infiltration and activity, crucial components of the immune response. Understanding the interplay between hypoxia-induced CAIX expression and tumor infiltrating lymphocytes (TIL) is essential to understand the mechanisms of anti-tumor immunity and immune-based therapeutic failure. Materials and Methods: Rectal adenocarcinoma tumor slides (n=68) were stained for CAIX with immunohistochemistry, and were categorized into four groups based on tumoral and stromal CAIX expression: T+/S+ (n=23), T+/S- (n=26), T-/S+ (n=4), and T-/S- (n=15). TIL were assessed across two compartments of the tumor; tumoral and peritumoral—to capture spatial distribution of immune cells. Infiltration was graded on a scale of 1–3 (low, moderate, high), reflecting immune cell density. Average TIL scores and standard deviations were calculated for both categories, and statistical comparisons were performed using unpaired t-tests to identify significant differences. Results: Significant differences in lymphocyte infiltration were found between the T+/S+ and T-/S- groups. T+/S+ samples exhibited lower infiltration in tumoral and peritumoral regions (tumoral: mean 1.48 ± 0.72 vs. 2.25 ± 0.71, p < 0.0026; peritumoral: mean 2.35 ± 0.64 vs. 2.80 ± 0.41, p < 0.0210). Conclusion: Tumor hypoxia, highlighted by CAIX influences lymphocyte infiltration, with higher expression correlating with diminished immune activity. This study highlights stromal CAIX’s role in immune evasion in rectal adenocarcinomas. Targeting stromal CAIX could disrupt its immune-suppressive effects, enhancing lymphocyte infiltration and activity. These findings justify further research into CAIX inhibitors and their potential in clinical applications.

Témavezető: Prof. Dr. Gábor Méhes

This study evaluated the expression of six tumor markers (BRAF, CK19, Gal-3, HBME-1, MIB-1, and p53) in 30 papillary thyroid carcinoma cases, 10 follicular thyroid carcinoma cases, and 40 control thyroid samples using immunohistochemical staining. BRAF, CK19, Gal-3, and HBME-1 effectively differentiated the papillary thyroid cancer from the follicular thyroid cancer and benign thyroid tissues, while MIB-1 and p53 distinguished malignant from benign cases. However, p53 did not show significant differences between the two types of the investigated thyroid cancer. These findings highlight the diagnostic value of these markers in distinguishing thyroid lesions, particularly in challenging cases.

Témavezető: CSONKA TAMAS

A copine-ok (CPNE) szolubilis vagy membrán-kötött, kalcium-függő és foszfolipid-kötő tulajdonságokkal rendelkező proteinek. Szerepük elsősorban jelátviteli folyamatokban, illetve membránok transzportjában van. A fehérjecsalád kilenc taggal rendelkezik (CPNE1-9), amelyek közül laboratóriumunk nyolcat (CPNE2-9) azonosított humán epidermális melanocitákban egészséges és daganatos pigmentsejtek sejtfelszíni fehérjéinek összehasonlító tömegspektrometriai vizsgálatai során. A UniProt adatbázis és az irodalom kevés információval rendelkezik a copine- okról melanocitákban, míg melanóma sejtekről egyáltalán nincsenek adatok. Jelen munkánk célja, hogy vizsgálatainkkal egészséges és daganatos pigmentsejtekben pontos képet kapjunk az egyes copine-ok expressziójáról és sejten belüli lokalizációjáról. Kísérleteinkhez általunk humán bőrből izolált melanocitákat, valamint in situ (WM35) és metasztatikus melanómából (A2058) létrehozott sejtvonalakat alkalmaztunk. A copine-ok mRNS expressziós vizsgálatához primereket terveztünk, majd a melanociták és melanóma sejtek copine expressziós mintázatait RT-qPCR segítségével határoztuk meg. A fehérjeexpresszió vizsgálatához western blotokat végeztünk teljes sejtlizátumokon, amelyek során a CPNE3, 6 és 7 kifejeződését ellenőriztük. Az analízis igazolta a vizsgált fehérjék expresszióját valamennyi sejtkultúrában. A CPNE3 és 6 esetében a melanóma sejtekben erősebb kemilumineszcens szignálokat kaptunk a melanocitákhoz képest, míg a CPNE7 expressziójában nem tapasztaltunk különbséget. Az immuncitokémiai reakciókat követő konfokális mikroszkópos elemzések a CPNE3, 6 és 7 erősebb immunpozitivitását igazolták a melanóma sejtekben a melanocitákhoz viszonyítva. Az immunfluoreszcens jelek diffúz eloszlást mutattak, ugyanakkor a CPNE7 inkább a melanociták nyúlványaiban, míg a CPNE6 a metasztatikus sejtek plazmamembránjához közeli területeken halmozódott. Munkánkkal humán melanóma sejtekben elsőként igazoltuk a copine-ok jelenlétét, továbbá pontos képet kaptunk az egészséges és daganatos pigmentsejtek copine expressziós mintázatai közötti eltérésekről. Kísérletes tapasztalataink hozzájárulhatnak klinikailag releváns új biomarkerek azonosításához, amelyek a melanóma korai azonosításában, kezelésében vagy követésében nagy jelentőséggel bírhatnak. A KULTURÁLIS ÉS INNOVÁCIÓS MINISZTÉRIUM EKÖP-24-2-DE-103 KÓDSZÁMÚ EGYETEMI KUTATÓI ÖSZTÖNDÍJ PROGRAMJÁNAK A NEMZETI KUTATÁSI, FEJLESZTÉSI ÉS INNOVÁCIÓS ALAPBÓL FINANSZÍROZOTT SZAKMAI TÁMOGATÁSÁVAL KÉSZÜLT.

Témavezető: Dr. Hajdú Tibor és Dr. Kovács Patrik

Astrocytes are a group of glial cells that are important in CNS function, and they have diverse morphology and physiology. In this project, we are looking into the morphological differences between human astrocytes and murine/mice astrocytes, more specifically regarding their soma and processes. This project aims to assess whether the already known differences between human and murine astrocytes can be well detected in our samples as well. For this project, we are analyzing the images of human and murine astrocytes that were collected from previous patched clamp experiments. Human and murine astrocytes were traced and analyzed. The astrocytes were marked with fluorescence. Human astrocytes were labeled with antibodies that targeted glial fibrillary acidic protein (GFAP), which is a common marker used against astrocytes. On the other hand, the murine astrocytes were labeled with Enhanced Yellow Fluorescence Protein (EYFP) or Tandem Dimer Tomato (tdTomato). Each slide was stacked with 10-30 image layers, providing a 3D view of the astrocyte. The tracing and analysis were conducted using the Neurolucida software. On the software, the astrocytes were traced layer by layer, marking their soma and processes. The diameter of the processes could also be adjusted on Neurolucida. Afterward, the Neurolucida Explorer could reconstruct the tracing as a 3D image, in addition to providing quantitative data on the soma and processes. Regarding the soma, its perimeter, area, feret minimum, feret maximum, compactness, and roundness were calculated. As for the processes, their quantity, nodes, ends, length, surface, and area were analyzed. Upon collecting these data, T-tests were conducted, comparing each characteristic of human and murine astrocytes. The T-test results have indicated differences in the astrocytic processes’ length and surface. Moreover, there are also differences in astrocytic soma’s perimeter, convexity, form factor and solidity. In several parameters of the processes, human astrocytes were significantly larger than the murine ones which is in line with the previous knowledge on the interspecies differences. With this research, we can confirm that our methods are suitable for detection the morphological and functional differences of murine and human astrocytes.

Témavezető: Balázs Pal

A mély nyaki régióban jelentős számban megtalálható barna adipocitákban az Uncoupling protein (UCP) 1 hőt állít elő. Ez a katabolikus folyamat nagymennyiségű makro- és mikrotápanyagot igényel, amelyeket a sejtek főleg a solute carrier (SLC) transzporterek segítségével veszik fel. Korábbi vizsgálataink feltárták, hogy a tiamin (B1 vitamin) jelenléte nélkülözhetetlen a humán barna adipociták hőtermelésének adrenerg jel általi aktivációja során. Szabad hozzáférésű egyedi sejtmagi RNS-szekvenálási adatok elemzésekor azt találtuk, hogy a tiamin transzporter (TT) 2-őt kódoló SLC19A3 expressziója feldúsult a humán nyaki-eredetű barna adipocitákban. Így célul tűztük ki annak vizsgálatát, hogy a TT2 gátlása hogyan befolyásolja a termogenezis adrenerg stimulációját ezen sejtekben. Primer szubkután és mély nyaki zsírszövet-eredetű sztróma sejteket adipocitákká differenciáltattunk 14 napon át, majd sejtpermeábilis dibutiril (db)-cAMP kezeléssel modelleztük a hőtermelés aktivációját 10 órán keresztül, a TT2 farmakológiai inhibitora (fedratinib) jelenlétében vagy hiányában. RNS izolálást követően teljes sejtes („bulk”) RNS- szekvenálást és RT-qPCR-t végeztünk, a vizsgált gének fehérje-szintű kifejeződését western blottal határoztuk meg. Az aktiváció előtt és után begyűjtött kondicionált tápfolyadékokból mértük az aminosav fluxust. Az adipociták oxigénfogyasztását Seahorse XF96 Extracellular Flux Analyzer-rel elemeztük. A TT2 gátlása fékezte a hőtermeléshez nélkülözhetetlen gének expressziójának db-cAMP általi felregulációját, valamint csökkentette az adipociták proton-csorgásos légzését, amely az UCP1-függő termogenezist tükrözi. RNS- szekvenálási adataink azt mutatták, hogy a fedratinib megváltoztatta az adipociták globális transzkriptómját adrenerg stimuláció során. A hőtermeléssel összefüggő számos gén és fehérje, például a TGM2, ID1 és NNMT kifejeződése alacsonyabb volt a TT2 gátlásának következtében. Ezenkívül a fedratinib a hőtermelés aktivációja során csökkentette az excitatórikus aminosav-transzporter 2-őt kódoló SLC1A2 expresszióját, a glutamin, glicin, tirozin, leucin és izoleucin felvételét, valamint a glükóz- és az aminosav-felhasználást tükröző etomoxir-rezisztens oxigénfogyasztást. Adataink azt sugallják, hogy a TT2 gátlása csökkenti a humán nyaki-eredetű barna adipociták adrenerg stimulációjának hatékonyságát a génexpresszió befolyásolásával és az aminosav-beáramlás korlátozásával. K. E. Szent-Györgyi Hallgató munkáját a Nemzeti Tudósképző Akadémia támogatja.

Témavezető: dr. Kristóf Endre Károly és dr. Arianti Rini

Az endometrium carcinoma 2023-ban megjelent új The International Federation of Gynecology and Obstetrics stádiumbesorolás a már meglévő 9 helyett 19+2 kategóriát soroltat fel. Ez jelentős változást eredményezhet a gyakorlatban, azonban még sem a National Comprehensive Cancer Network, sem az European Society of Gynaecological Oncology/ European Society for Radiotherapy and Oncology/ European Society of Pathology irányelvek sem vették még át a 2023-as stádiumbeosztás használatát. Retrospektív kohorsz vizsgálatot végeztünk a Debreceni Egyetem Klinikai Központjában nőgyógyászati onkoteam gyűlésre 2022.09.01. és 2023.08.31. között felterjesztett 199 endometrium carcinomás eseten. A vizsgálat célja megállapítani történt-e a 2023-as revízió alapján stádiumváltás, és ha igen, akkor az terápia befolyásoló-e. Továbbá megvizsgáltuk, hogy a klasszikus prognosztikai tényezők, a mismatch repair deficiencia és a p53 abnormalitás korrelálnak-e a daganat agresszivitásával. A tárgyévben a Polimeráz-ε-mutáció vizsgálata intézetünkben még nem került bevezetésre, ezért az IAm POLEmut még nem szerepel a stádiumok között. A p53 és mismatch repair fehérjék immunnhisztokémiája nem voltak kötelező elemei a diagnosztikának, így a IICm p53abn stádium sem került minden esetben felfedésre. Eredményeink azt mutatják, hogy nincs szignifikáns összefüggés a daganat agresszivitása és a mismatch repair fehérjék hiánya között, azonban a klasszikus kedvezőtlen prognosztikai tényezők és a p53 abnormalitás szignifikánsan gyakoribbak agresszív tumorokban, mint nem-agresszívekben. A stádiumkategóriák újradefiniálása az általunk megfigyelt 199 esetből 19 esetben jelentett potenciálisan terápia-befolyásoló kategóriaváltást. Egy nem-agresszív endometrium carcinoma stádiuma csökkent (IIIA→ IA3), míg nyolcé növekedett (hétnél IA vagy IB→ IIB, egy esetben IB→ IICm p53abn módosulás történt). Az agresszív endometrium carcinomák közül tíz esetben történt stádiumváltozás (öt esetben IA vagy IB→ IC, öt esetben IA vagy IB→ IIC változás történt). Bár a FIGO stádiumok számának bővítése önmagában még nem vált terápiás szempontból meghatározóvá, a vizsgálatunk alapján a változtatások a betegek jelentős, 9,55%-ában már most is különbséget eredményeznek a kezelési stratégiákban, még a molekuláris osztályozás alkalmazása nélkül is.

Témavezető: Deliné Dr. Molnár Sarolta és Dr. Juhász Péter