Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia

Diagn Pathol. 2011 Jul 5:6:59. doi: 10.1186/1746-1596-6-59.

Abstract

Background: D2-40 has been shown a selective marker for lymphatic endothelium, but also shown in the benign cervical basal cells. However, the application of D2-40 immunoreactivity in the cervical basal cells for identifying the grade of cervical intraepithelial neoplasia (CIN) has not been evaluated.

Methods: In this study, the immunoreactive patterns of D2-40, compared with p16(INK4A), which is currently considered as the useful marker for cervical cancers and their precancerous diseases, were examined in total 125 cervical specimens including 32 of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and p16(INK4A) immunoreactivities were scored semiquantitatively according to the intensity and/or extent of the staining.

Results: Diffuse D2-40 expression with moderate-to-strong intensity was seen in all the normal cervical epithelia (21/21, 100%) and similar pattern of D2-40 immunoreactivity with weak-to-strong intensity was observed in CIN1 (31/32, 97.2%). However, negative and/or focal D2-40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2%) and CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%). On the other hand, diffuse immunostaining for p16(INK4A) was shown in 37.5% of CIN1, 64.9% of CIN2, and 80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated with the p16(INK4A) immunoreactivity.

Conclusions: Immunohistochemical analysis of D2-40 combined with p16(INK4A) may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia, especially for distinguishing CIN1 from CIN2/3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived*
  • Antigens, Neoplasm / analysis*
  • Biomarkers, Tumor / analysis*
  • Chi-Square Distribution
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Down-Regulation
  • Female
  • Humans
  • Immunohistochemistry*
  • Neoplasm Grading
  • Nerve Tissue Proteins / analysis*
  • Predictive Value of Tests
  • Up-Regulation
  • Uterine Cervical Dysplasia / chemistry*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / chemistry*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ma2 antigen
  • Nerve Tissue Proteins
  • monoclonal antibody D2-40