None of the CRAs showed MMR deficiency (0.0 % vs. 5.6 %, CRA vs. CDA, p = 0.036), HER2 overexpression (0.0 % vs. 12.5 %, p = 0.001), or loss of PTEN expression (0.0 % vs. 9.7 %, p = 0.003).
The association with dMMR in HGEC with ARID1A/PTEN alterations, TP53 wild type expression pattern and unfavorable outcome suggests that different oncogenetic pathways within HGEC are present.
In contrast to previous reports, all but one of the tumours with PTEN gene mutations were microsatellite stable (MSI-), suggesting that PTEN is involved in a distinct pathway of colorectal tumorigenesis that is separate from the pathway of mismatch repair deficiency.
To determine whether PTEN is involved in the pathogenesis of EC arising in HNPCC cases, and whether PTEN inactivation precedes MMR deficiency, we obtained 41 ECs from 29 MLH1 or MSH2 mutation positive HNPCC families and subjected them to PTEN expression and mutation analysis.