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Lobular endocervical glandular hyperplasia is a neoplastic entity with frequent activating GNAS mutations.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2014 Mar; Vol. 38 (3), pp. 370-6. - Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- AMP-Activated Protein Kinase Kinases
Adenocarcinoma, Mucinous chemistry
Adenocarcinoma, Mucinous pathology
Adenocarcinoma, Mucinous virology
Adult
Aged
Biomarkers, Tumor analysis
Cervix Uteri chemistry
Cervix Uteri virology
Chromogranins
Cyclin-Dependent Kinase Inhibitor p16 analysis
DNA Mutational Analysis
DNA, Viral isolation & purification
Female
Genetic Predisposition to Disease
Human Papillomavirus DNA Tests
Humans
Hyperplasia
Immunohistochemistry
Middle Aged
Papillomaviridae genetics
Papillomaviridae isolation & purification
Phenotype
Protein Serine-Threonine Kinases genetics
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins p21(ras)
Uterine Cervical Neoplasms chemistry
Uterine Cervical Neoplasms pathology
Uterine Cervical Neoplasms virology
ras Proteins genetics
Adenocarcinoma, Mucinous genetics
Biomarkers, Tumor genetics
Cell Proliferation
Cervix Uteri pathology
GTP-Binding Protein alpha Subunits, Gs genetics
Mutation
Uterine Cervical Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 38
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 24145653
- Full Text :
- https://doi.org/10.1097/PAS.0000000000000093