Utility of Stathmin-1 as a Novel Marker in Evaluating Anal Intraepithelial Neoplasia (AIN)

Appl Immunohistochem Mol Morphol. 2019 Feb;27(2):134-139. doi: 10.1097/PAI.0000000000000547.

Abstract

The aim of this study is to determine whether immunohistochemistry for Stathmin-1 enhances diagnostic accuracy of anal dysplasia. The study included 40 biopsies with diagnosis of benign anal transitional zone (n=10), low-grade anal intraepithelial neoplasia (AIN) (AIN1, n=10), and high-grade AIN (AIN2, n=10, AIN3, n=10). The cases were selected to represent classic features. Immunohistochemistry for Stathmin-1, p16, and Ki-67 was performed and assessed for distribution within epithelial thickness. Stathmin-1 was expressed only in the basal layer of benign anal epithelium. Similar pattern of distribution was seen in all low-grade AIN cases (100%). In total, 40% of AIN2 showed Stathmin-1 staining pattern similar to AIN1. The other 60% of cases showed staining extending into the middle third of the epithelial thickness. Of AIN3 cases, 20% showed staining confined to the lower third epithelium, 20% showed staining extending to the middle third, and 60% showed staining extending into the upper third epithelium. The pattern of stain distribution suggested that staining extending above the lower one-third of the epithelial thickness discriminates between low-grade and high-grade AIN. With this cutoff, the sensitivity for the diagnosis of high-grade AIN was 70%, specificity was 100%, positive predictive value equaled 100%, and negative predictive value equaled 77%. P16INK4a showed 100% sensitivity for AIN2 and AIN3, whereas Ki-67 had 100% sensitivity for any AIN grade. In conclusion, Stathmin-1 has excellent specificity for the diagnosis of high-grade AIN; however, Stathmin-1 alone may not be sufficiently sensitive. Use in conjunction with other sensitive markers, such as p16 or Ki-67 may be considered.

MeSH terms

  • Anus Neoplasms / diagnosis*
  • Anus Neoplasms / metabolism
  • Biomarkers, Tumor / metabolism*
  • Carcinoma in Situ / diagnosis*
  • Carcinoma in Situ / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Precancerous Conditions
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Stathmin / metabolism*

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen
  • STMN1 protein, human
  • Stathmin