Increased expression of apoptosis-related protein 3 is highly associated with tumorigenesis and progression of cervical squamous cell carcinoma

Hum Pathol. 2013 Mar;44(3):388-93. doi: 10.1016/j.humpath.2012.05.028. Epub 2012 Oct 1.


The apoptosis-related protein 3 (APR3) gene was first cloned from HL-60 cells treated with all-trans-retinoic acid and was thought to be related to tumor cell apoptosis or differentiation. In this study, we sought to investigate its expression profile in cervical squamous cell carcinoma (SCC) and preneoplastic lesions to determine whether APR3 is involved in the malignant progression of SCC. The purified partial recombinant APR3 proteins were used to immunize rabbits for raising antibodies, and the specificity of the polyclonal anti-APR3 antibody was determined by enzyme-linked immunosorbent assay and Western blot. Sections were assessed for APR3 expression by immunohistochemistry in archived tissues from human normal cervix samples (n = 20), cervical intraepithelial neoplasia (n = 19), and invasive SCC (n = 52). Specific cytoplasmic immunostaining was evaluated for overall intensity and uniformity to derive a combined histoscore. The results of enzyme-linked immunosorbent assay and Western blot indicated that anti-APR3 antibody can serve as a good tool for research. The immunohistochemical analysis demonstrated an increased expression of APR3 in SCC relative to normal cervix epithelium and cervical intraepithelial neoplasia (P < .05). Strikingly, APR3 expression level was significantly higher in nonkeratinizing SCCs compared with keratinizing SCCs (P < .05) and higher in carcinomas with lymph node metastasis compared with cases without lymph node metastasis (P < .05). This study demonstrates that APR3 expression is increased significantly with malignant progression of human cervical SCC, and thus, it may serve as a potential biomarker to predict prognosis of cervical SCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Neoplasm
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / isolation & purification
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Transformation, Neoplastic
  • Cervical Intraepithelial Neoplasia / genetics
  • Cervical Intraepithelial Neoplasia / immunology
  • Cervical Intraepithelial Neoplasia / metabolism*
  • Cervical Intraepithelial Neoplasia / pathology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / metabolism*
  • Rabbits
  • Recombinant Proteins
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology


  • Antibodies, Neoplasm
  • Apoptosis Regulatory Proteins
  • Neoplasm Proteins
  • Recombinant Proteins
  • apoptosis related protein 3, human