Molecular, pathologic, and clinical features of early-onset endometrial cancer: identifying presumptive Lynch syndrome patients

Walsh MD, Cummings MC, Buchanan DD, Dambacher WM, Arnold S, McKeone D, Byrnes R, Barker MA, Leggett BA, Gattas M, Jass JR, Spurdle AB, Young J, Obermair A (2008) Molecular, pathologic, and clinical features of early-onset endometrial cancer: identifying presumptive Lynch syndrome patients. Clinical cancer research : an official journal of the American Association for Cancer Research 14:1692-1700

PURPOSE: A woman with early-onset endometrial cancer (EC) may represent the "sentinel" cancer event in a Lynch syndrome kindred. The aim of this study was to determine the incidence of Lynch syndrome in a series of young-onset EC, and to identify molecular, clinical, and pathologic features that may alert clinicians to the presence of this disorder. EXPERIMENTAL DESIGN: Patients with EC, ages < or="50" years,="" were="" identified="" from="" the="" queensland="" centre="" for="" gynaecological="" cancer.="" tumor="" sections="" underwent="" histopathology="" review="" and="" were="" immunostained="" for="" mismatch="" repair="" proteins.="" tumor="" dna="" was="" tested="" for="" microsatellite="" instability="" and="" methylation="" of="" mlh1.="" patients="" were="" conservatively="" classified="" as="" presumptive="" lynch="" syndrome="" if="" their="" tumors="" showed="" loss="" of="" at="" least="" one="" mismatch="" repair="" protein="" and="" were="" negative="" for="" methylation="" of="" mlh1.="" personal="" and="" family="" history="" of="" cancer="" was="" reviewed="" where="" available.="" results:="" presumptive="" lynch="" syndrome="" was="" seen="" in="" 26="" of="" 146="" (18%)="" tumors.="" these="" tumors="" were="" more="" likely="" to="" be="" poorly="" differentiated,="" international="" federation="" of="" gynecology="" and="" obstetrics="" stage="" ii="" and="" above,="" have="" tumor-infiltrating="" lymphocytes,="" have="" higher="" mitotic="" rate,="" and="" have="" deeper="" myometrial="" invasion="" (p="">< 0.05).="" lynch="" syndrome="" cases="" were="" more="" likely="" to="" be="" associated="" with="" a="" positive="" family="" history="" when="" analyzed="" for="" amsterdam="" criteria="" ii,="" diagnosis="" of="" a="" lynch="" syndrome="" spectrum="" cancer="" in="" at="" least="" one="" first-degree="" relative,="" and="" family="" history="" of="" any="" cancer="" (p="">< 0.05).="" conclusion:="" presumptive="" lynch="" syndrome="" was="" identified="" in="" 18%="" of="" early-onset="" ec.="" a="" risk="" of="" this="" magnitude="" would="" argue="" for="" routine="" immunohistochemical="" testing="" of="" tumors="" in="" patients="" diagnosed="" with="" ec="" at="" or="" before="" the="" age="" of="" 50="">