Lynch syndrome--related endometrial carcinomas show a high frequency of nonendometrioid types and of high FIGO grade endometrioid types

Int J Surg Pathol. 2010 Feb;18(1):21-6. doi: 10.1177/1066896909332117. Epub 2009 May 14.

Abstract

Although endometrial cancer (EC) represents the second most common cancer after colonic cancer in patients with Lynch syndrome (LS), the pathologic features and behavior of LS-related EC are not well recognized. ECs from 23 patients (mean age 46.2 years) with MSH2 (16), MLH1 (6), and MLH1/MSH2 (1) constitutional mutations were evaluated for histologic type, FIGO grade, FIGO stage, association with tumors in other sites, and survival. For every LS-associated tumor, 2 same-age cases from patients with no family history of LS-associated cancer were evaluated (sporadic group). In LS-associated EC there were 13 (56.5%) endometrioid (eec) and 10 (43.5%) nonendometrioid carcinomas (neec), and among the sporadic tumors there were 44 (95.7%) eec and 2 (4.3%) neec (P = .001). The eec in women with germline LS mutation had a significantly higher FIGO grade (P = .0378) and more frequent vascular invasion than the controls. The mean survival of the entire group of 23 patients with LS-related EC was 17.326 (14.066 to 20.585). Mean survival according to FIGO stage was significant (P = .010). Difference in mean survival according to age of the patient at the time of the diagnosis (patients >46 years vs <46 years) was not significant. The mean survival of the mutated patients with eec was 20.462 (17.564 to 23.359) and was not significantly different from that of the mutated patients with neec, which was 14.240 (9.119 to 19.361). Log-rank analysis showed that histology did not affect the survival. However, the hazard ratio of neec patients, although not significant, resulted higher. Mean survival of patients with a neec tumor combined with an endometrioid component (14.375 [8.084 to 20.666]) was not different from that of patients with pure neec cancers (14.250 [7.885 to 20.615]). When compared with the control population, LS-related ECs show a wider variety of histologic types; a higher frequency of neec types despite the younger age of the patients, and a higher frequency of high grades among the eec.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / mortality
  • Carcinoma, Endometrioid / pathology*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / mortality
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology*
  • DNA, Neoplasm / analysis
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology*
  • Female
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Staging
  • Nuclear Proteins
  • Polymorphism, Single-Stranded Conformational
  • Survival Rate

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Neoplasm
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein