WWP2 and its association with PTEN in endometrial cancer

• WWP2 is a ubiquitin ligase shown to degrade PTEN in previous studies.
• We investigated WWP2 levels in endometrial cancers.
• WWP2 levels in tumors with normal gene expression but loss of PTEN protein on IHC were compared to tumors without PTEN protein loss on IHC.
• WWP2 levels were significantly higher in tumors with normal gene expression but loss of PTEN protein on IHC

We wished to determine if WWP2 gene expression and PTEN protein levels inversely correlate in human endometrial cancer tissues. Fifty-one endometrioid endometrial tumors and five normal endometrial controls were available for analysis. PTEN protein levels were assessed by immunohistochemistry (IHC). WWP2 and PTEN gene expression were quantitated by RT PCR. Clinical and pathologic information was collected by chart review.We found that in tumors with low PTEN protein but normal mRNA expression there were significantly higher levels of WWP2 expression (p = 0.0017). Increased WWP2 expression was not associated with clinical prognostic factors including lymphovascular space invasion, ≥ 50% myometrial invasion, grade, stage or recurrence. WWP2 expression was not different statistically between tumors and normal controls (p = NS). Therefore, in this cohort, tumors with low PTEN protein but normal mRNA expression had elevated levels of WWP2 expression. This suggests that WWP2 may be playing a role in PTEN degradation in endometrial cancer.