Pathogenetic pathways in ovarian endometrioid adenocarcinoma: a molecular study of 29 cases

Am J Surg Pathol. 2009 Aug;33(8):1157-63. doi: 10.1097/PAS.0b013e3181a902e1.


It has been recently suggested that ovarian serous carcinoma follows a dualistic pathway with low-grade carcinomas arising from borderline tumors and high-grade carcinomas originating de novo. Similarly, our group has shown that based on their molecular profile endometrioid borderline tumors could predate low-grade endometrioid ovarian carcinomas (EOC). It is not clearly understood if low-grade EOC is in turn related to high-grade EOC, or if high-grade EOC may also arise de novo. The aim of our study was to compare the molecular profile of grade 1, 2, and 3 EOCs. Twenty-nine EOCs were selected including 10 grade 1 (G1), 11 grade 2 (G2), and 8 grade 3 (G3). Selected blocks were immunostained with beta-catenin and p53, and also microdissected, DNA extracted and amplified by polymerase chain reaction with primers for exon 3 of the beta-catenin gene, codons 12 and 13 of KRAS and codons 1 to 9 of PTEN. The length of BAT-26 and BAT-25 was analyzed to determine microsatellite instability (MSI). Patients with G1 EOC ranged from 21 to 71 (mean 52) years, those with G2 tumors ranged from 43 to 66 (mean 56) years, and patients with G3 EOC ranged from 41 to 67 (mean 57) years. Immunohistochemical analysis for beta-catenin showed nuclear staining in 14 cases (7 G1, 5 G2, and 2 G3 tumors), whereas the rest showed membranous staining. Beta-catenin mutations were found in only 3 G1 tumors. KRAS mutations were seen in 5 EOCs (2 G1 and 3 G2). MSI and mutations of PTEN were both detected in 1 G1 and 1 G2 tumor, respectively. There was no overlapping expression of MSI, beta-catenin, PTEN, or KRAS mutations. Finally, p53 overexpression was present in 6 EOCs (5 G3 and 1 G2), all G3 p53 positive tumors being negative for all other markers, whereas the G2 tumor also showed a KRAS mutation. In conclusion, beta-catenin and KRAS mutations, and MSI were strongly associated with low-grade EOC. In contrast, p53 overexpression characterized high-grade EOC, with no other molecular alterations present in the vast majority of these tumors. On the basis of these results, we suggest that there may also be a dual pathogenetic pathway for EOC.

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / pathology*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mutation
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Polymerase Chain Reaction


  • Biomarkers, Tumor