Loss of PTEN expression is an independent predictor of favourable survival in endometrial carcinomas.
BACKGROUND
We and others previously reported the prognostic significance of PTEN mutational status on favourable survival in endometrial carcinomas. Here, we demonstrate that loss of PTEN expression in immunohistochemistry is an independent prognostic marker for favourable survival in endometrial carcinomas.


METHODS
We conducted immunohistochemical analyses of PTEN, PIK3CA, phosphorylated Akt (p-Akt), and p27 in primary endometrial carcinomas from 221 patients. Mutation of PTEN was analysed further.


RESULTS
Expression of PTEN was lost in 56 patients (25%), and PIK3CA was overexpressed in 159 patients (72%). Overexpression of PIK3CA was associated with p-Akt overexpression (P<0.001), which was in turn associated with loss of nuclear p27 expression (P=0.028). Loss of PTEN expression was found to be associated with endometrioid histology (P=0.03), and was inversely associated with the presence of lymphovascular space invasion (P=0.03). Univariate and multivariate survival analyses revealed that factors of PTEN loss, age <70, histological grade 1, early International Federation of Gynecology and Obstetrics (FIGO) stage, and absence of lymphovascular invasion were independent prognostic indicators for better overall survival (P=0.03, 0.04, 0.01, <0.001, and 0.03, respectively). The subset analysis showed a stronger tendency of PTEN loss towards favourable survival in advanced-stage (III and IV) disease than in early-stage (I and II) disease (P=0.05 vs 0.14). Moreover, our mutational analysis demonstrated that PTEN expression loss was associated with PTEN-truncating mutations (P=0.03).


CONCLUSIONS
The current observations further support the prognostic significance of PTEN aberration on favourable outcome in endometrial carcinomas, providing useful implications for the individualised management of the disease.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
A
A
Akiyama-Abe
T
T
Minaguchi
Y
Y
Nakamura
H
H
Michikami
A
A
Shikama
S
S
Nakao
M
M
Sakurai
H
H
Ochi
M
M
Onuki
K
K
Matsumoto
T
T
Satoh
A
A
Oki
H
H
Yoshikawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000172:deficiency* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D010766:Phosphorylation; D016019:Survival Analysis
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human