Positive Surgical Margin, HPV Persistence, and Expression of Both TPX2 and PD-L1 Are Associated with Persistence/Recurrence of Cervical Intraepithelial Neoplasia after Cervical Conization

PLoS One. 2015 Dec 1;10(12):e0142868. doi: 10.1371/journal.pone.0142868. eCollection 2015.

Abstract

Objective: To determine the clinicopathologic and immunohistochemical predictors of the persistence/recurrence of cervical intraepithelial neoplasia (CIN) after cervical conization.

Methods: Medical records of 502 patients who received cervical conization treatment of CIN between 2005 and 2012 were reviewed. The clinicopathologic parameters were analyzed using Cox hazard regression. Fifty patients with CIN persistence/recurrence were matched to 50 cases without CIN persistence/recurrence. These 100 cervical specimens were assessed for expression of insulin-like growth factor II messenger RNA (mRNA)-binding protein 3 (IMP3), targeting protein for xenopus kinesin-like protein 2 (TPX2), and programmed cell death-1 ligand-1 (PD-L1) using immunohistochemical staining.

Results: Multivariate analysis found that the independent predictors of CIN persistence/recurrence were positive surgical margin (hazard ratio 5.777, 95% confidence interval 2.334-14.301, p < 0.001) and human papilloma virus persistence for 6 months (hazard ratio 20.685, 95% confidence interval 7.350-57.657, p < 0.001). Co-expression of TPX2 and PD-L1 was significantly higher in CIN persistence/recurrence group than the group without CIN persistence/recurrence (p = 0.013). The depth of glandular involvement (GI) was less than 3mm in about 86.8% (59/68) CIN2-3 lesions, However, No statistically significant associations between GI and persistence/recurrence were observed (P = 0.58).

Conclusion: Positive surgical margin, HPV persistence, and expression of both TPX2 and PD-L1 are associated with persistence/recurrence of cervical intraepithelial neoplasia after cervical conization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation
  • Cervix Uteri / pathology
  • Cervix Uteri / surgery*
  • Conization*
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Papillomaviridae / physiology*
  • RNA-Binding Proteins / metabolism
  • Recurrence
  • Risk
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / surgery
  • Uterine Cervical Dysplasia / virology*
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Cell Cycle Proteins
  • IGF2BP3 protein, human
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • RNA-Binding Proteins
  • TPX2 protein, human