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Start arrow Autosomalne dominujące arrow Zespół Lyncha

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Epidemiologia

Stanowi około 5 % wszystkich raków jelita grubego.
Średni wiek wystąpienie nowotworu złośliwego jelita grubego wynosi 44 lata.

Etiopatogeneza

Mutacja jednego z sześciu genów odpowiedzialnych za naprawę DNA: hMSH2 (human mutS homolog 2) na chromosomie 2p16, hMLH1 (human mutL homolog 1) na 3p21, hPMS1 i hPMS2 (human postmeiotic segregation 1 and 2) na 2q31 i 7q11, hMSH6 na 2p16 i hMSH3 na 5q11.2-q13.2. Najczęstsze to hMSH2 i hMLH1.
Choroba jest dziedziczona jako cecha autosomalna dominująca.
W przeważającej części (ok. 70 %) rak występuje w prawej połowie okrężnicy. Cechuje go niski stopień zróżnicowania, częste występowanie nacieków limfocytarnych w badaniu histopatologicznym, szybki wzrost miejscowy i niewielka tendencja do tworzenia przerzutów odległych. Pomimo niewrażliwości na chemioterapię lepiej rokuje. W zespole Lyncha jest większa proporcja guzów produkujących śluz. Występują też częściej niż w populacji ogólnej symetryczne gruczolaki.

Podział

1.    Zespół Lyncha I - rak dotyczy tylko jelita grubego.
2.    Zespół Lyncha II - z rakiem jelita grubego współistnieją nowotwory złośliwe macicy, jajnika, żołądka, skóry lub nerek.
Współistnienie zespołu Lyncha z guzami gruczołów łojowych określa się jako zespół Muir-Torre, a z guzami ośrodkowego układu nerwowego jako zespół Turcota.

Rozpoznanie

 Kryteria amsterdamskie II z 1999 r.
1.    Trzech lub więcej krewnych z histologicznie potwierdzonym rakiem jelita grubego, w tym jeden krewny pierwszego stopnia w stosunku do pozostałych.
2.    Rak jelita grubego występujący co najmniej w dwóch pokoleniach.
3.    Jeden lub więcej przypadków raka jelita grubego w rodzinie, rozpoznanych przed 50. rokiem życia.
Aby rozpoznać zespół Lyncha muszą być spełnione wszystkie trzy kryteria. Należy wykluczyć wcześniej zespół polipowatości rodzinnej, a zachorowania na raka jelita grubego musi być potwierdzone badaniem histopatologicznym.
 Badanie niestabilności mikrosatelitarnej
Ze względu na zawodność kryteriów amsterdamskich stosuje się przesiewowe badanie pod kątem występowania niestabilności mikrosatelitarnego DNA w tkance guza wg wytycznych Bethesda. Alternatywnie, badanie ekspresji hMLH1, hMSH2 i hMSH6 metodami immunohistochemicznymi.

 Wytyczne Bethesda

1.    Rodziny spełniające kryteria amsterdamskie I.
2.    Osoby, u których rozpoznano 2 zachorowania ze spektrum zespołu Lynch, z uwzględnieniem synchronicznych i metachronicznych zachorowań na raka jelita grubego i na inne nowotwory o lokalizacji pozajelitowej.
3.    Chorzy na raka jelita grubego z jednym krewnym pierwszego stopnia, który zachorował na ten sam nowotwór lub inny ze spektrum HNPCC przed 45. rokiem życia lub u którego rozpoznano gruczolaka w jelicie grubym przed 45. rokiem życia.
4.    Chorzy, u których raka jelita grubego lub raka trzonu macicy rozpoznano przed 45. rokiem życia.
5.    Chorzy z rakiem części wstępującej jelita grubego lub odbytnicy rozpoznanym przed 45. rokiem życia, w badaniu histologicznym nowotwór niezróżnicowany lub typu carcinoma solidum/cribriforme.
6.    Chorzy na raka jelita grubego poniżej 45. roku życia, w badaniu histologicznym komórki sygnetowate.
7.    Osoby, u których gruczolaki jelita grubego stwierdzono przed 40. rokiem życia.

Leczenie

Patrz - rak jelita grubego.
Osoby spokrewnione z chorymi wymagają badań genetycznych i kolonoskopowych co 2-3 lata, zaczynając w 25. roku życia lub w wieku przynajmniej o 5 lat młodszym niż najwcześniejszy przypadek raka jelita grubego w rodzinie. U kobiet dodatkowo obowiązuje ocena ginekologiczna z ultrasonografią narządu rodnego i ewentualną biopsją błony śluzowej

 

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