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Differenzialdiagnostik erblicher Dickdarmkarzinomsyndrome

Der Beitrag der Pathologie

Differential diagnostics of hereditary colorectal cancer syndromes

The role of pathology

Zusammenfassung

Etwa ein Drittel der kolorektalen Karzinome (KRK) treten familiär gehäuft auf, wobei etwa 5% einen monogenetischen Erbgang aufweisen. Diagnostisch hilfreich ist die Unterscheidung zwischen Erkrankungen mit und ohne Polyposis sowie die Berücksichtigung von Tumorhistologie und Tumorspektrum des jeweiligen Patienten. Etwa 1% der KRK lassen sich auf die familiäre adenomatöse Polyposis coli (FAP) mit rasenartig vermehrten (>100) Adenomen zurückführen. Weitere 2–3% betreffen das nicht mit Polyposis assoziierte HNPCC- bzw. Lynch-Syndrom, für welches als einzigem Darmkrebssyndrom ein molekularer Gewebetest zur Verfügung steht. Immunhistochemisch erfolgt zunächst die Prüfung auf einen Verlust der Expression eines Mismatch-Reparatur-Gens, woran sich bei unsicherem oder negativem Ergebnis der Test auf Mikrosatelliteninstabilität (MSI) anschließt. Im Unterschied zu den vorgenannten Syndromen wird die MYH-assoziierte Polyposis (MAP) rezessiv vererbt und weist nur mäßig erhöhte Polypenzahlen (im Mittel 15–30) auf. Sie ist differenzialdiagnostisch von attenuierten Formen der FAP mit <100 Polypen abzugrenzen. Bei Verdacht auf ein familiäres Tumorsyndrom ist in jedem Fall eine humangenetische Beratung anzuschließen, in deren Rahmen letztlich die Indikation zu einer weitergehenden molekulargenetischen Testung (Nachweis einer Keimbahnmutation) gestellt wird.

Abstract

One third of colorectal carcinomas (CRC) show familial clustering of which about 5% have a monogenetic trait. Distinction between disease with and without polyposis, tumor histology and tumor spectrum in a given patient are all of diagnostic relevance. Familial adenomatous polyposis (FAP) underlies approximately 1% of CRC characterized by rapidly forming (>100) adenomas. In contrast to these about 2%–3% of CRC have a hereditary background without polyposis (HNPCC). This is the only hereditary tumour syndrome to date for which a tissue-based molecular screening test is available. Accordingly, expression analysis of mismatch repair genes (MSH2, MSH6 and MLH1, PMS2) is performed first. In the case of an equivocal result with no complete loss of expression testing of microsatellite instability (MSI) is added. In contrast to the other diseases MYH-associated polyposis (MAP) follows a recessive trait with polyp numbers usually between 15–30 adenomas and should be distinguished from attenuated forms of FAP with <100 polyps in the differential diagnosis. In the case of suspected familial cancer syndrome genetic counseling is warranted in order to decide ultimately whether there is an indication for genetic testing (evidence of a germ-line mutation).

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Abbreviations

ACF:

„Aberrant crypt focus“ (frühe oligokryptale Läsion)

AFAP:

Attenuierte adenomatöse Polyposis coli

APC:

Adenomatosis polyposis coli

CIMP:

„CpG island methylation pathway“ (Promotormethylierung)

CIN:

Chromosomale Instabilität

CS:

Cowden-Syndrom

FAP:

Familiäre adenomatöse Polyposis

FJP:

Familiäre juvenile Polypose

HNPCC:

Hhereditäres nicht-polypöses Kolonkarzinom

HP:

Hyperplastischer Polyp

HPP:

Hyperplastische Polyposis

KRAS/BRAF:

Onkogene Proteinkinasen zur intrazellulären Signaltransduktion

KRK:

Kolorektales Karzinom

MAP:

MYH-assoziierte Polyposis

MGMT :

O-6-Methylguanin-DNA Methyltransferase (Reparaturgen)

MSH2, MSH6, MLH1, PMS2:

Mismatch-Reparatur-Gene

MSI:

Mikrosatelliteninstabilität, hoch (MSI-H), niedrig (MSI-L)

MSS:

Mikrosatellitenstabil

p53 :

Onkogen

PJS:

Peutz-Jeghers-Syndrom

SPS:

„Serrated pathway syndrome“

5JÜLR:

5-Jahres-Überlebensrate

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Correspondence to J. Rüschoff.

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Herrn Prof. Dr. P. Propping in dankbarer Anerkennung seiner Arbeit als Sprecher der Studiengruppe des Verbundprojektes „Erblicher Darmkrebs“ der Deutschen Krebshilfe (seit 1999).

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Rüschoff, J., Heinmöller, E., Hartmann, A. et al. Differenzialdiagnostik erblicher Dickdarmkarzinomsyndrome. Pathologe 31, 412–422 (2010). https://doi.org/10.1007/s00292-010-1352-8

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  • DOI: https://doi.org/10.1007/s00292-010-1352-8

Schlüsselwörter

  • Hereditäre Kolonkarzinomsyndrome
  • Familiäre adenomatöse Polyposis coli
  • MYH-assoziierte Polyposis
  • Hereditäres nichtpolypöses kolorektales Karzinom
  • Hamartomatöse Polyposissyndrome

Keywords

  • Hereditary colon cancer syndromes
  • Familial adenomatous polyposis coli
  • MYH associated polyposis
  • Hereditary nonpolyposis colorectal cancer
  • Hamartomatous polyposis syndromes