Is lobular endocervical glandular hyperplasia a cancerous precursor of minimal deviation adenocarcinoma?: a comparative molecular-genetic and immunohistochemical study

Am J Surg Pathol. 2008 Dec;32(12):1807-15. doi: 10.1097/PAS.0b013e3181883722.

Abstract

Although lobular endocervical glandular hyperplasia (LEGH) was originally described as a distinct hyperplastic glandular lesion of the uterine cervix, recent studies have raised a question that LEGH may be a cancerous precursor of minimal deviation adenocarcinoma (MDA) and other mucinous adenocarcinomas (MACs) of the uterine cervix. In the present study, we studied LEGH, MDA, and MAC by using molecular-genetic and immunohistochemical methods for chromosomal imbalance, microsatellite instability, human papillomavirus (HPV) infection, and gastric pyloric-type mucin secretion to clarify their relationship. Comparative genomic hybridization revealed recurrent chromosomal imbalances, that is, gains of chromosome 3q and a loss of 1p, which were common to MDA and MAC, in 3 of 14 LEGHs analyzed (21%). LEGHs with chromosomal imbalances showed a degree of cellular atypia in the hyperplastic glandular epithelium. Dual-color fluorescence in situ hybridization confirmed a gain of chromosome 3 fragment in these cervical glandular lesions. HPV in situ hybridization revealed that high-risk HPV (types 16 and 18) was positive in over 80% of MACs, but negative in all LEGHs and MDAs examined. Microsatellite instability was rarely detected in these cervical glandular lesions. Our present study results demonstrated a molecular-genetic link between LEGH and cervical mucinous glandular malignancies including MDA and MAC, and are thought to support the hypothesis that a proportion of LEGHs are cancerous precursors of MDA and/or MAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / virology
  • Adult
  • Aged
  • Cervix Uteri / pathology*
  • Comparative Genomic Hybridization
  • Female
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Microsatellite Instability
  • Middle Aged
  • Papillomavirus Infections
  • Polymerase Chain Reaction
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / virology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology