Somatic Testing on Gynecological Cancers Improve the Identification of Lynch Syndrome.
Int J Gynecol Cancer
; 27(7): 1543-1549, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-28471861
ABSTRACT
OBJECTIVE:
Recent data from the literature indicate gynecological cancers (GCs) as sentinel cancers for a diagnosis of Lynch syndrome (LS). Clinical approaches to identifying LS have low sensitivity, whereas somatic tests on GCs may be a more sensitive and cost-effective strategy.METHODS:
A series of 78 GCs belonging to 74 patients sent to the Genetic Counselling Service were investigated using microsatellite instability, immunohistochemical expression of mismatch repair (MMR) genes, and MLH1 promoter methylation.RESULTS:
The presence of microsatellite instability was observed in 67.5% of GCs, and the absence of immunohistochemical expression of at least 1 of the 4 MMR proteins was observed in 71.4% of GCs, showing 96.1% concordance between the methods. Methylation analysis using methylation specific multiplex ligation-dependent probe amplification performed on 35 samples revealed MLH1 promoter hypermethylation in 18 cases (54%). Molecular analysis identified 36 LS carriers of MMR variants (27 pathogenetic and 9 variants of uncertain significance), and, interestingly, 3 LS patients had MLH1 methylated GC.With regard to histological features, LS-related GCs included endocervical cancers and also histological types different from the endometrioid cancers. The presence of peritumoral lymphocytes in GCs was statistically associated with LS tumors.CONCLUSIONS:
Somatic analysis is a useful strategy to distinguish sporadic from LS GC. Our data allow the identification of a subset of LS patients otherwise unrecognized on the basis of clinical or family history alone. In addition, our results indicate that some clinicopathological features including age of GC diagnosis; presence of peritumoral lymphocytes; isthmic, endocervical sites, and body mass index value could be useful criteria to select patients for genetic counseling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms, Hereditary Nonpolyposis
/
Genital Neoplasms, Female
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Int J Gynecol Cancer
Journal subject:
GINECOLOGIA
/
NEOPLASIAS
Year:
2017
Type:
Article
Affiliation country:
Italy