PIK3CA mutations in endometrial carcinomas in Chinese women: phosphatidylinositol 3′-kinase pathway alterations might be associated with favorable prognosis

Dong, Ying; Yang, Xi; Wong, Oscar; Zhang, Xiaoming; Liang, Ying; Zhang, Ying; Wong, Wei; Nong, Lin; Liao, Qinping; Li, Ting

doi:10.1016/j.humpath.2011.08.021

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PIK3CA mutations in endometrial carcinomas in Chinese women: phosphatidylinositol 3′-kinase pathway alterations might be associated with favorable prognosis☆☆☆

Ying Dong, MD
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China
Xi Yang, MD
- Department of Gynecology and Obstetrics, The Peking University, First Hospital, Beijing 100034, China
Oscar Wong, PhD
- Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
Xiaoming Zhang, PhD
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China
Ying Liang, MD
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China
Ying Zhang
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China
Wei Wong, MD
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China
Lin Nong, PhD
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China
Qinping Liao, MD
- Department of Gynecology and Obstetrics, The Peking University, First Hospital, Beijing 100034, China
- Corresponding author.
Ting Li, MD
- Department of Pathology, The Peking University, First Hospital, Beijing 100034, China

Received 22 June 2011; received in revised form 24 August 2011; accepted 26 August 2011. published online 03 January 2012.
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Summary

The aim of this study was to determine the clinicopathological impact of PIK3CA mutations and phosphatidylinositol 3′-kinase pathway alterations in endometrial cancers in Chinese women. The PIK3CA mutation status was analyzed by sequencing in 94 tumors. The status of phosphatase and tensin homolog, p-(Ser/Thr)AKT, human epidermal growth factor receptor 2, p53, and estrogen and progesterone receptor was assessed in 102 tumors using immunohistochemistry. Biomarker status was correlated with clinicopathologic variables and with patient survival. We found that 28 mutations occurred in the helical domain encoded by exon 9 of PIK3CA and 16 occurred in the kinase domain (exon 20). Mutations of both exons were more common in low-grade than in high-grade endometrioid carcinomas, and the correlation between exon 9 mutation and lower grade was statistically significant (P = .045). In univariate analysis, phosphatidylinositol 3′-kinase pathway activation (defined as PIK3CA mutation and/or phosphatase and tensin homolog loss) was associated with a favorable prognosis (P = .034) and showed an increased predictive power when combined with expression of p-AKT, the phosphatidylinositol 3′-kinase pathway downstream effector (P = .022). In multivariate analysis, phosphatidylinositol 3′-kinase pathway activation was not an independent predictor of disease-free survival (P = .091). Interestingly, in the estrogen receptor–negative subgroup, the phosphatidylinositol 3′-kinase pathway alteration was significantly related to prolonged patient survival (P = .048), whereas this association was not present in the estrogen receptor–positive subgroup (P > .05). Our findings suggest that phosphatidylinositol 3′-kinase pathway alteration might have a favorable prognostic impact on endometrial cancers in Chinese women. Furthermore, the function of the phosphatidylinositol 3′-kinase pathway might be affected by estrogen receptor status.

Keywords: PIK3CA mutations, PI3K-AKT pathway alteration, Prognosis, Endometrial carcinomas, Chinese women