Expression of placental leucine aminopeptidase is associated with a poor outcome in endometrial endometrioid adenocarcinoma.
OBJECTIVE
Placental leucine aminopeptidase (P-LAP) is a cell surface aminopeptidase (oxytocinase). We cloned P-LAP cDNA and found a widespread tissue distribution of P-LAP. Since P-LAP can degrade several small peptide hormones such as oxytocin, this enzyme may affect many cellular functions of carcinoma cells as well as normal cells. This study investigated whether the expression of P-LAP correlates with clinicopathologic factors and prognosis in patients with endometrial endometrioid adenocarcinoma.


METHODS
Histologic sections of formalin-fixed, paraffin-embedded specimens from 99 primary endometrial carcinomas were stained for P-LAP using polyclonal P-LAP antibody. Disease-free survival and other clinicopathologic characteristics were analyzed according to the intensity of P-LAP staining.


RESULTS
Of 99 cases, 69 (69.7%) showed specific P-LAP immunostaining. We found a positive correlation between the expression of P-LAP and histological grade (p < 0.01), surgical stage of the disease (p = 0.02), myometrial invasion (p = 0.01), lymph node involvement (p < 0.01), and vascular infiltration (p < 0.01). In patients who had strongly positive P-LAP staining, the disease-free interval was significantly lower than in patients who had negative or weakly positive P-LAP staining (p < 0.01). Multivariate analysis demonstrated that strongly immunoreactive P-LAP (odds ratio, 12.8; 95% confidence interval, 2.84-58.8; p < 0.01) and surgical stage (odds ratio, 8.78; 95% confidence interval, 2.77-27.8; p < 0.01) are independent prognostic factors.


CONCLUSIONS
This study suggests P-LAP as an independent prognosticator of clinical outcome in patients with endometrial carcinoma. Therefore, assessment of the P-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma.
Shibata
Kiyosumi
K
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan. shiba@med.nagoya-u.ac.jp
Kikkawa
Fumitaka
F
Suzuki
Yuka
Y
Mizokami
Yayoi
Y
Kajiyama
Hiroaki
H
Ino
Kazuhiko
K
Nomura
Seiji
S
Nagasaka
Tetsuro
T
Mizutani
Shigehiko
S
D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000201:enzymology* / Q000473:pathology*; D010122:Cystinyl Aminopeptidase / Q000032:analysis*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase