[Colorectal Carcinoma with Suspected Lynch Syndrome: A Multidisciplinary Algorithm].
Lynch syndrome is the most frequent hereditary cancer syndrome, accounting for approximately 3-5 % of all colorectal cancers. In addition, it is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. In clinical practise Lynch syndrome is frequently not detected and many clinicians admit uncertainties regarding diagnostic procedures. Also, counselling of patients is considered difficult regarding therapeutic - especially prophylactic surgical and chemopreventive options and recommendations. Based on a review of available literature we discuss optimized strategies for improved detection of suspected Lynch syndrome patients. The aim of this review is to establish a clinical algorithm of how to proceed on a diagnostic level and to discuss surgical options at the time of a colorectal cancer. In order to identify patients with Lynch syndrome, family history should be ascertained and evaluated in regards to fulfilment of the Amsterdam-II- and/or the revised Bethesda criteria. Subsequently immunohistochemical staining for the mismatch-repair-genes, BRAF testing for MLH1 loss of expression, as well as testing for microsatellite instability in some, followed by genetic counselling and mutation analysis when indicated, is recommended. Pathological identification of suspected Lynch syndrome is readily feasible and straightforward. However, the need of performing these analyses in the tumor biopsy at the time of (gastroenterological) diagnosis of CRC neoplasia is essential, in order to offer patients the option of a prophylactically extended surgery and - as recommended in the German S3 guidelines - to discuss the option of a merely prophylactical hysterectomy and oophorectomy (if postmenopausal) in women. Close cooperation between gastroenterologists, pathologists and surgeons is warranted, so that patients may benefit from options of extended or prophylactically extended surgery at the time of diagnosis of a colorectal primary. Patients nowadays must be involved in informed decision-making regarding prophylactic or extended prophylactic surgery at the time of a colorectal primary. To date, however, limitations in daily clinical practise, the failure to assess family history and the lack of awareness of this important hereditary syndrome is the major asset leading to severe underdiagnosis and putting to risk the indexpatients themselves and their families to (metachronous) CRC and the associated extracolonic cancers. If at all tumors of patients fulfilling Bethesda criteria will be analysed for MSI in the surgical specimen and therefore Lynch syndrome patients are not given the opportunity to opt for extended surgery. In clinical experience the postoperative MSI-analysis is inconsistently performed - even if the Bethesda criteria are fulfilled - and in case of suspected Lynch syndrome genetically counselling is not consistently recommended. Therefore affected cancer patients are left unaware of their increased genetic risk and in average 3 high-risk gene carriers per family miss the opportunity to actively engage in the recommended screening program.
Klinik für Visceral-, Thorax- und Gefäßchirurgie, Philipps-Universität Marburg, Deutschland.
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Schneider
Klinik für Allgemein- und Viszeralchirurgie, HELIOS St. Josefs-Hospital, Bochum-Linden, Deutschland.
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Schneider
Institut für Pathologie, Universitätsklinikum Köln, Deutschland.
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Büttner
Abteilung für Hämatologie und Onkologie, St. Josef-Hospital der Ruhr-Universität Bochum, Deutschland.
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Reinacher-Schick
Institut für Pathologie, Universitätsklinikum Bochum, Deutschland.
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Tannapfel
Klinik für Chirurgie, Caritas-Krankenhaus St. Josef, Regensburg, Deutschland.
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Fürst
Institut für Pathologie Nordhessen, Kassel, Deutschland.
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Rüschoff
Klinik für Innere Medizin, Gastroenterologie, HELIOS St. Josefs-Hospital, Bochum-Linden, Deutschland.
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Jakobeit
Institut für Humangenetik, Heinrich-Heine-Universität Düsseldorf, Deutschland.
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Royer-Pokora
Klinik für Allgemein- und Viszeralchirurgie, HELIOS St. Josefs-Hospital, Bochum-Linden, Deutschland.
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Möslein
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000465:Algorithms; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D003299:Cooperative Behavior; D053843:DNA Mismatch Repair / Q000235:genetics; D004252:DNA Mutational Analysis; D005817:Genetic Counseling; D019983:Guideline Adherence; D006801:Humans; D033183:Interdisciplinary Communication; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D059467:Transcriptome / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1