TY - JOUR AU - Krencz, Ildikó AU - Sztankovics, Dániel AU - Sebestyén, Anna AU - Pápay, Judit AU - Dankó, Titanilla AU - Moldvai, Dorottya AU - Lutz, Elmar AU - Khoor, Andras TI - RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 SN - 1219-4956 DO - 10.3389/pore.2024.1611593 UR - https://m2.mtmt.hu/api/publication/34805614 ID - 34805614 AB - RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy. LA - English DB - MTMT ER - TY - JOUR AU - Fűr, Gabriella Mihalekné AU - Nemes, Kolos AU - Magó, Éva AU - Benő, Alexandra Á. AU - Topolcsányi, Petronella AU - Moldvay, Judit AU - Pongor, Lőrinc S. TI - Applied models and molecular characteristics of small cell lung cancer JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 SP - 1 EP - 13 PG - 13 SN - 1219-4956 DO - 10.3389/pore.2024.1611743 UR - https://m2.mtmt.hu/api/publication/34803555 ID - 34803555 AB - Small cell lung cancer (SCLC) is a highly aggressive type of cancer frequently diagnosed with metastatic spread, rendering it surgically unresectable for the majority of patients. Although initial responses to platinum-based therapies are often observed, SCLC invariably relapses within months, frequently developing drug-resistance ultimately contributing to short overall survival rates. Recently, SCLC research aimed to elucidate the dynamic changes in the genetic and epigenetic landscape. These have revealed distinct subtypes of SCLC, each characterized by unique molecular signatures. The recent understanding of the molecular heterogeneity of SCLC has opened up potential avenues for precision medicine, enabling the development of targeted therapeutic strategies. In this review, we delve into the applied models and computational approaches that have been instrumental in the identification of promising drug candidates. We also explore the emerging molecular diagnostic tools that hold the potential to transform clinical practice and patient care. LA - English DB - MTMT ER - TY - JOUR AU - Orosz, Zsuzsanna AU - Kovács, Árpád TI - The role of chemoradiotherapy and immunotherapy in stage III NSCLC JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 SP - 1 EP - 6 PG - 6 SN - 1219-4956 DO - 10.3389/pore.2024.1611716 UR - https://m2.mtmt.hu/api/publication/34799242 ID - 34799242 AB - Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable non-small lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PD-L1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era. LA - English DB - MTMT ER - TY - JOUR AU - Jakab, Anna AU - Patai, Árpád V. AU - Darvas, Mónika AU - Tormássi-Bély, Karolina AU - Micsik, Tamás TI - Microenvironment, systemic inflammatory response and tumor markers considering consensus molecular subtypes of colorectal cancer JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 SP - 30:1611574 SN - 1219-4956 DO - 10.3389/pore.2024.1611574 UR - https://m2.mtmt.hu/api/publication/34796477 ID - 34796477 AB - Introduction: Colorectal carcinomas (CRC) are one of the most frequent malignancies worldwide. Based on gene expression profile analysis, CRCs can be classified into four distinct subtypes also known as the consensus molecular subtypes (CMS), which predict biological behaviour. Besides CMS, several other aspects of tumor microenvironment (TME) and systemic inflammatory response (SIR) influence the outcome of CRC patients. TME and inflammation have important role in the immune (CMS1) and mesenchymal (CMS4) subtypes, however, the relationship between these and systemic inflammation has not been assessed yet. Our objective was to evaluate the connection between CMS, TME and SIR, and to analyze the correlation between these markers and routinely used tumor markers, such as CEA (Carcinoembryonic Antigen) and CA19-9 (Carbohydrate Antigen 19-9). LA - English DB - MTMT ER - TY - JOUR AU - Gálffy, Gabriella AU - Morocz, Eva AU - Korompay, Reka AU - Hecz, Reka AU - Bujdoso, Reka AU - Puskas, Rita AU - Lovas, Timea AU - Gaspar, Eszter AU - Yahya, Kamel AU - Kiraly, Peter AU - Lohinai, Zoltán TI - Targeted therapeutic options in early and metastatic NSCLC-overview JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 21 SN - 1219-4956 DO - 10.3389/pore.2024.1611715 UR - https://m2.mtmt.hu/api/publication/34792203 ID - 34792203 AB - The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in similar to 15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations. LA - English DB - MTMT ER - TY - JOUR AU - Deme, Dániel AU - Bálint, F. Tamaskovics AU - Nizar, Jammoud AU - Kovács, Sándor AU - Emmanuel, O. Kayode AU - James, W. Grice AU - Telekes, András TI - Association between pathological characteristics and Recurrence Score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center /OncotypeDX in breast cancer JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 2024 PY - 2024 SN - 1219-4956 DO - 10.3389/pore.2024.1611735 UR - https://m2.mtmt.hu/api/publication/34779913 ID - 34779913 LA - English DB - MTMT ER - TY - JOUR AU - Batar, Peter AU - Alizadeh, Hussain AU - Rokszin, György Aurél AU - Abonyi-Tóth, Zsolt AU - Demeter, Judit TI - Corrigendum: Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 2 SN - 1219-4956 DO - 10.3389/pore.2024.1611758 UR - https://m2.mtmt.hu/api/publication/34773876 ID - 34773876 LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Andrea AU - Pálfi, Erzsébet AU - Belák, Barbara AU - Blasszauer, Célia AU - Reibl, Dániel AU - Lövey, József TI - Positive correlation between persistence of medical nutrition therapy and overall survival in patients with head and neck cancer JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 10 SN - 1219-4956 DO - 10.3389/pore.2024.1611664 UR - https://m2.mtmt.hu/api/publication/34744616 ID - 34744616 N1 - Health Sciences Division, Doctoral School of Semmelweis University, Budapest, Hungary Scientific Committee, National Association of Hungarian Dietitians, Budapest, Hungary Danone Hungary Kft., Budapest, Hungary Department of Dietetics and Nutritional Sciences, Semmelweis University, Budapest, Hungary Bacs-Kiskun County Hospital, Kecskemet, Hungary MedicalScan Kft., Budapest, Hungary National Tumour Biology Laboratory, National Institute of Oncology, Budapest, Hungary Department of Oncology, Semmelweis University, Budapest, Hungary Export Date: 19 April 2024 CODEN: POREF Correspondence Address: Molnár, A.; Health Sciences Division, Hungary; email: dr.molnarandrea.rd@gmail.com AB - Background: Several factors can affect overall survival of head and neck cancer (HNC) patients, including characteristics of the cancer disease and response to treatments. However, patients’ nutritional status and the effectiveness of medical nutrition therapy (MNT) can also impact overall survival. The primary goal of our research was to collect real-life data on the use of MNT in HNC patients and to specifically investigate the correlation between survival and the duration of uninterrupted (persistent) nutrition. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Árpád AU - Trási, Krisztina AU - Barabás, Márton AU - Gál, Kristóf AU - Csiki, Emese AU - Sipos, Dávid AU - Papp, Judit AU - Simon, Mihály TI - LINAC-based SBRT in treating early-stage NSCLC patients-single institution experience and survival data analysis JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 6 SN - 1219-4956 DO - 10.3389/pore.2024.1611589 UR - https://m2.mtmt.hu/api/publication/34725859 ID - 34725859 AB - Aim: This single institute prospective study aimed to evaluate the feasibility of LINAC-based stereotactic body radiotherapy (SBRT) in treating patients with early-stage non-small cell lung cancer (NSLSC). We focused on the survival data with the local and distant control profiles and the cancer- and non-cancer-specific survival. Treatment-related side effects were also collected and analyzed. Methods: Patients with early-stage NSCLC between January 2018 and October 2021 were included in our prospective study; a total of 77 patients receiving LINAC-based SBRT were analyzed. All patients had pretreatment multidisciplinary tumor board decisions on SBRT. The average patient age was 68.8 years (median: 70 years, range: 52-82); 70 patients were in ECOG 0 status (91%), while seven patients were in ECOG 1-2 status (9%). 52% of the patients (40) had histologically verified NSCLC, and the other 48% were verified based on PETCT results. We applied the SBRT scheme 8 x 7.5 Gy for central tumors (74%) or 4 x 12 Gy for peripheral tumors (26%). Results: The mean follow-up time was 25.4 months (median 23, range 18-50). The Kaplan-Meier estimation for overall survival in patients receiving LINAC-based SBRT was 41.67 months. Of the 77 patients treated by SBRT, death was reported for 17 patients (9 cases cancer-specific, 8 cases non-cancer specific reason). The mean local tumor control was 34.25 months (range 8.4-41), and the mean systemic control was 24.24 months (range 7-25). During the treatments, no Grade I-II were reported; in 30 cases, Grade I non-symptomatic treatment-related lung fibrosis and two asymptomatic rib fractures were reported. Conclusion: In the treatment of early-stage NSCLC, LINAC-based SBRT can be a feasible alternative to surgery. Although we reported worse OS data in our patient cohort compared to the literature, the higher older average age and the initial worse general condition (ECOG1-2) in our patient cohort appear to be the reason for this difference. With the comparable local control and survival data and the favorable side effect profile, SBRT might be preferable over surgery in selected cases. LA - English DB - MTMT ER - TY - JOUR AU - Sztankovics, Dániel AU - Moldvai, Dorottya AU - Petővári, Gábor AU - Dankó, Titanilla AU - Szalai, Fatime AU - Miyaura, Risa AU - Varga, Viktória AU - Nagy, Noémi AU - Papp, Gergő AU - Pápay, Judit AU - Krencz, Ildikó AU - Sebestyén, Anna TI - mTOR hyperactivity and RICTOR amplification as targets for personalized treatments in malignancies JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 19 SN - 1219-4956 DO - 10.3389/pore.2024.1611643 UR - https://m2.mtmt.hu/api/publication/34725263 ID - 34725263 AB - The increasing knowledge of molecular alterations in malignancies, including mutations and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway, highlights the importance of mTOR hyperactivity as a validated target in common and rare malignancies. This review summarises recent findings on the characterization and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity. We have recently identified new tumor types with RICTOR (rapamycin-insensitive companion of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets for developing targeted therapies in lung cancer and other newly described malignancies. The activity of mTOR complexes is recommended to be assessed and considered in cancers before mTOR inhibitor therapy, as current first-generation mTOR inhibitors (rapamycin and analogs) can be ineffective in the presence of mTORC2 hyperactivity. We have introduced and proposed a marker panel to determine tissue characteristics of mTOR activity in biopsy specimens, patient materials, and cell lines. Ongoing phase trials of new inhibitors and combination therapies are promising in advanced-stage patients selected by genetic alterations, molecular markers, and/or protein expression changes in the mTOR signaling pathway. Hopefully, the summarized results, our findings, and the suggested characterization of mTOR activity will support therapeutic decisions. LA - English DB - MTMT ER -