CPE overexpression is correlated with pelvic lymph node metastasis and poor prognosis in patients with early-stage cervical cancer

Arch Gynecol Obstet. 2016 Aug;294(2):333-42. doi: 10.1007/s00404-015-3985-6. Epub 2015 Dec 22.

Abstract

Purpose: Elevated carboxypeptidase E (CPE) levels play crucial roles in tumorigenesis and metastasis. This study investigated the expression and clinicopathological significance of CPE in early-stage cervical cancer.

Methods: Elevated carboxypeptidase E expression was analyzed using quantitative polymerase chain reaction and western blotting in normal cervical tissue, cervical cancer cell lines, and in cervical cancer tissues and adjacent noncancerous tissues (ANTs) from the same patient. Immunohistochemistry (IHC) was used to examine CPE expression in tissue samples from 112 patients with early-stage cervical cancer (FIGO stages Ia2-IIa2), 60 patients with cervical intraepithelial neoplasia, and 19 patients with normal cervical tissues (NCTs). Associations between CPE expression and prognostic and diagnostic factors were evaluated statistically.

Results: CPE expression was significantly higher in cervical cancer cell lines and tissues than in normal tissues and ANTs. Semi-quantitative analysis of IHC indicated that CPE gradually increased from CIN I to cervical cancer, but was absent in NCTs. CPE expression was seen in 40.2 % (45/112) of the cervical cancer samples. CPE expression was significantly associated with FIGO stage (P = 0.003), tumor size (P = 0.012), stromal invasion (P < 0.001), lymphovascular space invasion (P = 0.016), parametrial infiltration (P = 0.027), vaginal involvement (P = 0.007), postoperative adjuvant therapy (P = 0.024), recurrence (P < 0.001), survival (P < 0.001), and pelvic lymph node metastasis (PLNM) (P < 0.001), and it was significantly higher in tissues from patients with PLNM than without PLNM. Logistic regression analysis identified high-level CPE expression as an independent risk factor for PLNM (P = 0.001). Patients with higher CPE expression had shorter overall survival duration than patients with lower CPE expression. Univariate and multivariate Cox-regression analyses suggested that high-level CPE expression is an independent prognostic factor for overall survival in early-stage cervical cancer.

Conclusions: High-level CPE expression was associated with a poor prognosis in early-stage cervical cancer. CPE may serve as a biomarker for predicting PLNM and survival in these patients.

Keywords: CPE; Cervical cancer; Pelvic lymph node metastasis; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carboxypeptidase H / genetics
  • Carboxypeptidase H / metabolism*
  • Cervical Intraepithelial Neoplasia / metabolism*
  • Cervical Intraepithelial Neoplasia / mortality
  • Cervical Intraepithelial Neoplasia / pathology
  • China / epidemiology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Pelvis / pathology*
  • Polymerase Chain Reaction
  • Prognosis
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Carboxypeptidase H