Lobular endocervical glandular hyperplasia is a neoplastic entity with frequent activating GNAS mutations

Akiko Matsubara, Shigeki Sekine, Reiko Ogawa, Masayuki Yoshida, Takahiro Kasamatsu, Hitoshi Tsuda, Yae Kanai

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


To clarify the significance of GNAS mutations in cervical tumorigenesis, we performed mutational analyses in a total of 154 lesions and in 22 normal tissues of the uterine cervix. Activating GNAS mutations were found in 8 of the 19 lobular endocervical glandular hyperplasias (LEGH; 42%) and 4 of the 79 endocervical-type mucinous adenocarcinomas (5%) but were never seen in the normal endocervical tissue, minimal deviation adenocarcinomas, endometrioid adenocarcinomas, or squamous cell carcinomas. We further examined the presence of human papillomavirus (HPV) DNA and p16 expression to probe the relationship between GNAS mutations and HPV infection in LEGHs and carcinomas. All the GNAS-mutated LEGHs were negative for HPV DNA and p16 expression, whereas all the GNAS-mutated adenocarcinomas were positive for HPV DNA and/or p16 expression, implicating GNAS mutations in the development of LEGH and a minor subset of HPV-related cervical adenocarcinomas. Additional mutational analyses of LEGH identified KRAS and STK11 mutations in 1 and 2 cases, respectively. The GNAS, KRAS, and STK11 mutations were mutually exclusive; thus, a total of 11 LEGHs (58%) had 1 of these genetic alterations. Although LEGH has been regarded as a metaplastic lesion, the frequent presence of genetic alterations suggests a neoplastic nature.

Original languageEnglish
Pages (from-to)370-376
Number of pages7
JournalAmerican Journal of Surgical Pathology
Issue number3
Publication statusPublished - 2014 Mar
Externally publishedYes


  • GNAS
  • KRAS
  • STK11
  • lobular endocervical glandular hyperplasia
  • uterine cervix

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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