Ferenc Pinter

Publications (4)26.62 Total impact

• Article: Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone.

  Peter Balla, Linda Moskovszky, Zoltan Sapi, Ramses Forsyth, Helen Knowles, Nick A Athanasou, Miklos Szendroi, Laszlo Kopper, Hajnalka Rajnai, Ferenc Pinter, Istvan Petak, Maria Serena Benassi, Piero Picci, Amalia Conti, Tibor Krenacs
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  ABSTRACT: Epidermal growth factor receptor (EGFR) is implicated in bone remodelling. The aim was to determine whether EGFR protein expression contributes to the aggressiveness and recurrence potential of giant cell tumour of bone (GCTB), an osteolytic primary bone tumour that can exhibit markedly variable clinical behaviour. Immunohistochemical analysis on tissue microarrays (TMA) of 231 primary, 97 recurrent, 17 metastatic and 26 malignant GCTBs was performed using TMA analysis software and whole digital slides allowing validated scoring. EGFR expression was restricted to neoplastic stromal cells and was significantly more frequent in recurrent (71 of 92; 77%) than in non-recurrent GCTBs (86 of 162; 53%) (P = 0.002); and in clinicoradiologically aggressive (31 of 43; 72%) than latent (27 of 54; 50%) cases (P = 0.034). Detecting phosphotyrosine epitopes pY1068 and -pY1173 indicated active EGFR signalling, and finding EGFR ligands EGF and transforming growth factor-α restricted to cells of the monocytic lineage suggested paracrine EGFR activation in stromal cells. In functional studies EGF supported proliferation of GCTB stromal cells, and the addition of EGF and macrophage-colony stimulating factor promoted osteoclastogenesis. In GCTB, EGFR signalling in neoplastic stromal cells may contribute to disease progression through promoting stromal cell proliferation and osteoclastogenesis.
  Histopathology 09/2011; 59(3):376-89. · 3.08 Impact Factor
• Article: Epidermal growth factor receptor (EGFR) high gene copy number and activating mutations in lung adenocarcinomas are not consistently accompanied by positivity for EGFR protein by standard immunohistochemistry.

  Ferenc Pinter, Judit Papay, Andrea Almasi, Zoltan Sapi, Edit Szabo, Melinda Kanya, Anna Tamasi, Balazs Jori, Edit Varkondi, Judit Moldvay, Klara Szondy, Gyorgy Keri, Massimo Dominici, Pierfranco Conte, Sandor Eckhardt, Laszlo Kopper, Richard Schwab, Istvan Petak
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  ABSTRACT: The purpose of this study was to investigate whether detectable protein biomarker overexpression is a prerequisite for the presence of increased gene copy number or activating mutations and responsiveness to the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib in patients with lung adenocarcinomas. EGFR status was prospectively analyzed in tumor biopsy samples by three methods: protein expression (n = 117) by standardized immunohistochemistry (IHC), gene copy number (n = 97) by fluorescent in situ hybridization (FISH), and mutation analysis by sequencing (n = 126). Fifty-nine percent of the samples were positive by IHC, 40% were positive by FISH, and 13.5% contained activating kinase domain mutations. Thirty-four percent of the FISH-positive and 27% of the mutant samples were also IHC-negative. All EGFR mutant patients had major clinical responses (five complete response and five partial response) to gefitinib or erlotinib treatment, although three of these tumors were IHC-negative and four were FISH-negative. In a retrospective analysis of samples from nine patients with excellent therapeutic responses (three complete response, five partial response, one stable disease) to erlotinib or gefitinib, mutations were identified in eight cases, but IHC was negative in four of these tumors. These results indicate that molecular diagnostic methods appear to be most important for the identification of lung adenocarcinoma patients who may benefit from EGFR inhibitor treatments.
  Journal of Molecular Diagnostics 04/2008; 10(2):160-8. · 3.58 Impact Factor
• Article: Biochemical assay-based selectivity profiling of clinically relevant kinase inhibitors on mutant forms of EGF receptor.

  Edit Varkondi, Ferenc Pinter, Kiss Robert, Richard Schwab, Nora Breza, Laszlo Orfi, György Keri, Istvan Petak
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  ABSTRACT: Gefitinib and erlotinib are potent EGFR tyrosine kinase inhibitors (potentially) useful for the treatment of non-small-cell lung cancer (NSCLC). Clinical responses, however, in NSCLC patients have been linked to the presence of certain activating mutations of EGFR. We used an ELISA-based biochemical assay to confirm the selective inhibitory efficacy of gefitinib and erlotinib on the activated mutant receptor. Our results are in line with the clinical observations providing evidence for the predictive power of the kinase assay. Four additional compounds were also investigated: CI-1033 and EKB-569 had dramatic inhibitory effects on all EGFR forms, whereas PD153035 and AG1478 were active on wild-type and activating mutant protein. In docking simulations with wild-type EGFR, our inhibitory data are in good agreement with the binding scores. These data confirm that anilinoquinazolines are good starting structures for the next generation of selective drugs against mutant EGFR, whereas CI-1033 and EKB-569 may represent advances for patients with both wild-type and anilinoquinazoline-resistant mutant tumors.
  Journal of Receptor and Signal Transduction Research 02/2008; 28(3):295-306. · 1.59 Impact Factor
• Source

  Available from: Gyorgy Kéri

  Article: Modern treatment of lung cancer: case 1. Amplification and mutation of the epidermal growth factor receptor in metastatic lung cancer with remission from gefitinib.

  Richard Schwab, Ferenc Pinter, Judit Moldavy, Judi Papay, Janos Strausz, Laszlo Kopper, Gyorgy Keri, Akos Pap, Istvan Petak, Karoly Oreskovich, Laszlo Mangel
  Journal of Clinical Oncology 11/2005; 23(30):7736-8. · 18.37 Impact Factor