Significance of phosphoinositide 3 kinase/AKT pathway alterations in endometrial carcinoma / 中华病理学杂志
Chinese Journal of Pathology
;
(12): 799-804, 2011.
Article
in Chinese
| WPRIM
| ID: wpr-358231
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSIONS</b>Endometrial 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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Phosphorylation
/
General Surgery
/
Signal Transduction
/
Receptors, Progesterone
/
Receptors, Estrogen
/
Exons
/
Survival Rate
/
Follow-Up Studies
/
Endometrial Neoplasms
Type of study:
Observational study
/
Prognostic study
Limits:
Adult
/
Aged
/
Female
/
Humans
Language:
Chinese
Journal:
Chinese Journal of Pathology
Year:
2011
Type:
Article
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