Prognostic implications of the coexisting precursor lesion types in invasive gallbladder cancer

Hum Pathol. 2021 Aug:114:44-53. doi: 10.1016/j.humpath.2021.05.001. Epub 2021 May 11.

Abstract

Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P < 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.

Keywords: Biliary intraepithelial neoplasia; Gallbladder carcinoma; Intracholecystic papillary neoplasms; p16; p53.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • CDX2 Transcription Factor / analysis
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Female
  • Gallbladder Neoplasms / chemistry
  • Gallbladder Neoplasms / mortality
  • Gallbladder Neoplasms / pathology*
  • Gallbladder Neoplasms / surgery
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mucins / analysis
  • Neoplasm Invasiveness
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / mortality
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / surgery
  • Prognosis
  • Ribonucleoproteins, Small Nucleolar / analysis
  • Risk Assessment
  • Risk Factors
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • IMP3 protein, human
  • Mucins
  • Ribonucleoproteins, Small Nucleolar
  • TP53 protein, human
  • Tumor Suppressor Protein p53