Significance of HER2 and Ki-67 in Preneoplastic Lesions and Carcinoma of Gallbladder

J Gastrointest Cancer. 2019 Dec;50(4):848-854. doi: 10.1007/s12029-018-0162-8.


Background: HER2 is an oncoprotein which is overexpressed in several cancers including breast and stomach. Several studies have shown that HER2 is overexpressed in gallbladder cancer and in precancerous lesions. The present study was undertaken to assess pattern and level of expression of HER2 in metaplasia, dysplasia, and different stages of gallbladder carcinoma, which would determine its suitability as a prognostic biomarker in neoplastic transformation of gallbladder epithelium. The study was also aimed at to find the significance of Ki-67 index in these lesions.

Methods and materials: One hundred and twenty-eight patients who underwent cholecystectomy comprised the study group. Among them, 108 (84.4%) specimens showing metaplasia, dysplasia, and carcinoma on routine histopathology were considered as cases and 20 (15.6%) specimens of chronic cholecystitis having non-metaplastic mucosa were considered as control. Immunohistochemistry (IHC) was performed for HER2 and Ki-67. For HER2 interpretation ASCO/CAP guideline for breast cancer was followed. Chi-square test was used to find out the significance of HER2 expression in dysplasia/metaplasia/carcinoma. The ANOVA and Tukey-Kramer Multiple Comparisons Test were used for determining the association of Ki-67 with malignant transformation.

Results and conclusions: Overexpression of HER2 was observed in 48% (n = 12) of adenocarcinomas, 58% (n = 7) of high-grade dysplasia, 47% (n = 8) of low-grade dysplasia, and 74% (n = 25) of intestinal metaplasia. Ki-67 index increases in a non-linear fashion as the precursor lesions progress toward malignancy. In the future, these markers might be used as a prognostic biomarker for gallbladder carcinoma and its precursor lesions and it might become a valid indication for targeted therapies for gallbladder cancer.

Keywords: Adenocarcinoma of gallbladder; HER2; Ki-67; Preneoplastic conditions of gallbladder.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Cholecystectomy
  • Cholecystitis / pathology
  • Cholecystitis / surgery
  • Female
  • Gallbladder / pathology*
  • Gallbladder Neoplasms / diagnosis*
  • Gallbladder Neoplasms / pathology
  • Gallbladder Neoplasms / surgery
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism*
  • Male
  • Metaplasia / pathology
  • Metaplasia / surgery
  • Middle Aged
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / surgery
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • MKI67 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2