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8 results on '"Winand Dinjens"'

1. Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma Demonstrates High Intertumor and Intratumor Heterogeneity

Author

E.J.C.A. (Eline) Kamp, M.P. (Maikel) Peppelenbosch, M. (Michail) Doukas, Joanne Verheij, Cyriel Y. Ponsioen, R. (Ronald) van Marion, M.J. (Marco) Bruno, B. (Bas) Groot Koerkamp, W.N.M. (Winand) Dinjens, A.C. (Annemarie) de Vries, E.J.C.A. (Eline) Kamp, M.P. (Maikel) Peppelenbosch, M. (Michail) Doukas, Joanne Verheij, Cyriel Y. Ponsioen, R. (Ronald) van Marion, M.J. (Marco) Bruno, B. (Bas) Groot Koerkamp, W.N.M. (Winand) Dinjens, and A.C. (Annemarie) de Vries

Abstract

INTRODUCTION: Intertumor and intratumor heterogeneity may explain the diagnostic challenge and limited efficacy of chemotherapy for primary sclerosing cholangitis-associated cholangiocarcinoma (PSC-CCA). In this study, tumor heterogeneity was assessed through p53 and p16 protein expression analysis and next-generation sequencing (NGS) of TP53 and CDKN2A genetic alterations in PSC-associated CCA. METHODS: Formalin-fixed paraffin-embedded tissue samples from resection material of patients with PSC-CCA or patients with PSC diagnosed with biliary dysplasia were selected. Sections with CCA and foci with dysplastic epithelium were identified by 2 independent gastrointestinal pathologists. Immunohistochemical evaluation of p53 and p16 protein expression and NGS of TP53 and CDKN2A genetic alterations were performed. RESULTS: A total of 49 CCA and 21 dysplasia samples were identified in the resection specimens of 26 patients. P53 protein expression showed loss of expression, wild type, and overexpression in 14%, 63%, and 23% CCA and in 19%, 62%, and 19% dysplasia samples, respectively. P16 protein expression showed negative, heterogeneous, and positive results in 31%, 57%, and 12% CCA and in 33%, 53%, and 14% dysplasia samples, respectively. NGS showed high intertumor and intratumor heterogeneity of TP53 mutations and CDKN2A loss. Nearly 70% of the samples with a TP53 missense mutation demonstrated p53 overexpression, whereas all samples with a TP53 nonsense mutation demonstrated loss of p53 protein expression. DISCUSSION: PSC-associated CCA is characterized by high intertumor and intratumor heterogeneity of both p53/p16 protein expression and genetic alterations in TP53/CDKN2A, indicating that these tumors consist of multiple subclones with substantially different genetic makeup. The high intertumor and intratumor heterogeneity in PSC-CCA should be acknowledged during the development of diagnostic and therapeutic strategies.

Published
2021
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2. Malignant transformation of salivary gland pleomorphic adenoma

Author

Matthijs H. Valstar, H. (Hetty) Mast, Ivo ten Hove, L.R. (Laura) Moonen, Alfons J.M. Balm, Ludi E. Smeele, Senada Koljenović, W.N.M. (Winand) Dinjens, M.F. (Marie-Louise) van Velthuysen, Matthijs H. Valstar, H. (Hetty) Mast, Ivo ten Hove, L.R. (Laura) Moonen, Alfons J.M. Balm, Ludi E. Smeele, Senada Koljenović, W.N.M. (Winand) Dinjens, and M.F. (Marie-Louise) van Velthuysen

Abstract

Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for ag

Published
2021
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6. Donor-transmitted metastasis of colorectal carcinoma in a transplanted liver

Author

Zuzana, Zelinkova, Ina, Geurts-Giele, Joanne, Verheij, Herold, Metselaar, Winand, Dinjens, Hendrikus Jan, Dubbink, and Pavel, Taimr

Subjects
Male, Genotype, Liver, Liver Cirrhosis, Alcoholic, Contrast Media, Humans, Ultrasonics, Middle Aged, Neoplasm Metastasis, Colorectal Neoplasms, Liver Transplantation
Abstract

A 62-year-old man with alcoholic liver cirrhosis underwent liver transplantation. The transplantation went uneventful and the ultrasound imaging of the liver performed after transplantation did not show any abnormalities. Eighteen months later, an intra-hepatic focal lesion was found on ultrasound. A contrast-enhanced ultrasound revealed a lesion with a malignant pattern of contrast uptake. The histo-pathological and subsequent molecular-pathological analysis concluded a colorectal metastasis of donor origin. The donor had no history of malignancy but no complete autopsy had been performed which illustrates the importance of the meticulous donors` screening. Transplanted patients carry a high risk of developing malignancy in general but donor related-tumors are very rare. The therapeutic considerations differ substantially between recipient- and donor-related malignancies. Therefore, considering the possibility of donor-related tumor by raising suspicion of malignant lesion with appropriate imaging and distinction from recipient-related malignancy by molecular analysis are crucial for proper therapeutic decision.

Published
2011

7. Microsatellite instability of germ cell tumors is associated with resistance to systemic treatment

Author

Frank, Mayer, Ad J M, Gillis, Winand, Dinjens, J Wolter, Oosterhuis, Carsten, Bokemeyer, and Leendert H J, Looijenga

Subjects
Adult, Male, Adolescent, Nuclear Proteins, DNA, Neoplasm, Middle Aged, Immunohistochemistry, Disease-Free Survival, Neoplasm Proteins, Seminoma, DNA-Binding Proteins, MutS Homolog 2 Protein, Testicular Neoplasms, Drug Resistance, Neoplasm, Proto-Oncogene Proteins, Antineoplastic Combined Chemotherapy Protocols, Humans, Germinoma, Cisplatin, Carrier Proteins, MutL Protein Homolog 1, Adaptor Proteins, Signal Transducing, Aged, Microsatellite Repeats
Abstract

Systemic cisplatin-based chemotherapy curesor =90% of patients with metastatic germ cell tumors (GCTs). The biological basis of this exquisite chemo-sensitivity and the resistant phenotype encountered in 10-15% of patients with GCT is yet unclear. A defective mismatch repair pathway leading to microsatellite instability (MSI) has been related to resistance to cytotoxic drugs. We investigated 100 unselected GCTs and 11 clinically defined chemotherapy-resistant GCTs for MSI using 8 mono- or dinucleotide markers and the presence of the mismatch repair factors MLH1, MSH2, and MSH6 by immunohistochemistry. The resistant tumors, both chemo-naïve (n = 8) and pretreated (n = 3), showed a significantly higher incidence of MSI compared with the unselected series (45 versus 6% in at least one locus and 36 versus 0% inor =2 of 8 loci, both Por = 0.001). In 5 of all 11 unstable tumors, MSI correlated with immunohistochemical findings. This study demonstrates for the first time a positive correlation between MSI and treatment resistance in GCT.

Published
2002

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