Significance of phosphoinositide 3 kinase/AKT pathway alterations in endometrial carcinoma.
- Author:
Xi YANG
1
;
Ying DONG
;
Xiao-ming ZHANG
;
Ying LIANG
;
Ying ZHANG
;
Yi-ting MENG
;
Ying WANG
;
Wei WANG
;
Lin NONG
;
Ting LI
;
Qin-Ping LIAO
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Carcinoma, Endometrioid; genetics; metabolism; pathology; surgery; Class I Phosphatidylinositol 3-Kinases; Endometrial Neoplasms; genetics; metabolism; pathology; surgery; Exons; Female; Follow-Up Studies; Humans; Hysterectomy; Middle Aged; Mutation; Neoplasm Invasiveness; Neoplasm Staging; PTEN Phosphohydrolase; metabolism; Phosphatidylinositol 3-Kinases; genetics; metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt; metabolism; Receptors, Estrogen; metabolism; Receptors, Progesterone; metabolism; Signal Transduction; Survival Rate
- From: Chinese Journal of Pathology 2011;40(12):799-804
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women.
METHODSThe expression of PTEN, p-AKT, and ER/PR was assessed in 71 cases of endometrial carcinoma by immunohistochemistry (EnVision method). The PIK3CA mutation at exon 9 and exon 20 was analyzed by PCR and direct sequencing in 34 tumors.
RESULTS(1) Of the 71 cases of endometrial carcinoma, 65 cases were endometrioid adenocarcinoma (EEC) and 6 cases were nonendometrioid adenocarcinoma (NEEC). PTEN loss of expression was found in 63.4% (45/71) of tumors, and more commonly occurred in EEC (66.2%, 43/65) than that in NEEC (2/6, P = 0.18). Patients with PTEN loss in their tumors (45 cases) had a better survival than those without (26 cases, P = 0.07). In ER negative subgroup, the patients with PTEN loss of expression (12 cases) had longer survival than those with normal PTEN expression (7 cases; P = 0.04). (2) The frequency of PIK3CA mutation was 41.2% (14/34) with a hot mutation spot at T544 in exon 9. PIK3CA mutations more commonly occurred in EEC (44.8%, 13/29) than in NEEC (1/5, P > 0.05). The mutations at exon 9 more commonly occurred in EEC, well- and moderately-differentiated EEC, and tumors at early stage (P > 0.05). On the contrary, in tumors at early stages, the frequency of mutations in exon 20 (14.3%, 4/28) was significantly lower than that at late stages (4/6, P = 0.01). (3) p-AKT was positive in 59.2% (42/71) of tumors that were more frequently found in EEC (60.0%, 39/65) than that in NEEC (3/6, P = 0.68). However, the significant difference of p-AKT expression was found between well- and moderately-differentiated EEC (75.0%, 21/28; 53.6%, 15/28) and poorly-differentiated EEC (3/9, P = 0.02). Moreover, p-AKT expression was significantly correlated with positive ER (r = 0.339, P = 0.00).
CONCLUSIONSEndometrial carcinoma patients with loss of PTEN and p-AKT positivity have a favorable prognosis. PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis. The function of PTEN loss and p-AKT expression may vary according to different hormone status.
