Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance.

Autor: Ahadova A; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Pfuderer PL; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Ahtiainen M; Department of Education and Research, Central Finland Central Hospital, 40620 Jyväskylä, Finland., Ballhausen A; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Bohaumilitzky L; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Kösegi S; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Müller N; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Tang YL; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Kosmalla K; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Witt J; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Endris V; Department of General Pathology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany., Stenzinger A; Department of General Pathology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany., von Knebel Doeberitz M; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Bläker H; Institute of Pathology, University Hospital Leipzig, 04103 Leipzig, Germany., Renkonen-Sinisalo L; Department of Gastrointestinal Surgery, Helsinki University Hospital, 00290 Helsinki, Finland., Lepistö A; Department of Gastrointestinal Surgery, Helsinki University Hospital, 00290 Helsinki, Finland., Böhm J; Department of Pathology, Central Finland Central Hospital, 40620 Jyväskylä, Finland., Mecklin JP; Department of Education and Research, Central Finland Central Hospital, 40620 Jyväskylä, Finland.; Faculty of Sports and Health Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland., Seppälä TT; Department of Gastrointestinal Surgery, Helsinki University Hospital, 00290 Helsinki, Finland.; Department of Surgical Oncology, Johns Hopkins University, Baltimore, MD 21287, USA., Kloor M; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2021 Jun 01; Vol. 10 (11). Date of Electronic Publication: 2021 Jun 01.
DOI: 10.3390/jcm10112458
Abstrakt: Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high-throughput coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs ( n total = 95). Incident cancers presented with lower UICC and T stage compared to prevalent cancers ( p < 0.0005). The majority of incident cancers (21/28) were detected after previous colonoscopy without any pathological findings. On the molecular level, incident cancers presented with a significantly lower KRAS codon 12/13 (1/23, 4.3% vs. 11/21, 52%; p = 0.0005) and pathogenic TP53 mutation frequency (0/17, 0% vs. 7/21, 33.3%; p = 0.0108,) compared to prevalent cancers; 10/17 (58.8%) incident cancers harbored one or more truncating APC mutations, all showing mutational signatures of mismatch repair (MMR) deficiency. The proportion of MMR deficiency-related mutational events was significantly higher in incident compared to prevalent CRC ( p = 0.018). In conclusion, our study identifies a set of features indicative of biological differences between incident and prevalent cancers in LS, which should further be monitored in prospective LS screening studies to guide towards optimized prevention protocols.
Databáze: MEDLINE
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