Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Cancer Genomics Proteomics. 2020 Sep-Oct;17(5):627-641. doi: 10.21873/cgp.20219.

Abstract

Background/aim: We investigated differences in the clinicopathological and molecular characteristics between gastric-type mucinous carcinoma (GMC) and usual-type endocervical adenocarcinoma (UEA).

Patients and methods: We collected the clinicopathological information and performed targeted genomic sequencing analysis.

Results: GMCs exhibited significantly deeper invasion depth, larger horizontal spread, more advanced stage, more frequent distant metastasis, and more frequent parametrial and vaginal extension. Disease-free survival time of GMC patients was significantly shorter than that of UEA patients. GMCs displayed mutant p53 immunostaining pattern, whereas UEAs exhibited p16 block positivity. GMCs harbored mutations in KRAS, TP53, NF1, CDKN2A, STK11, and ARID1A. One GMC exhibited MDM2 amplification. In contrast, UEAs harbored mutations in HRAS, PIK3CA, and BRCA2. Two UEAs were found to have novel TP53 mutations.

Conclusion: GMC is associated with more aggressive behavior than UEA. Distinctive p53 and p16 immunostaining patterns enable differential diagnosis. GMC and UEA exhibit genetic heterogeneity with potentially actionable molecular alterations.

Keywords: Uterus; cervix; gastric-type mucinous carcinoma; immunohistochemistry; targeted sequencing; usual-type endocervical adenocarcinoma.

MeSH terms

  • Adenocarcinoma, Mucinous / diagnosis*
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / surgery
  • Adult
  • Biomarkers, Tumor / genetics*
  • Cervix Uteri / pathology*
  • Cervix Uteri / surgery
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Diagnosis, Differential
  • Disease-Free Survival
  • Female
  • Humans
  • Hysterectomy
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Retrospective Studies
  • Tumor Suppressor Protein p53
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • TP53 protein, human
  • Tumor Suppressor Protein p53