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Loss of heterozygosity analysis in uterine cervical adenocarcinoma
Kentaro Miyai1, Yoshiaki Furugen, Toshiharu Matsumoto
1Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.
Objective:
Uterine cervical adenocarcinoma (CAC) is a rare form of cervical cancer, constituting only 5-8% of all cervical epithelial malignancies. Loss of heterozygosity (LOH) analysis of CAC was undertaken to identify alterations of chromosomal loci that may play important roles in the development of this tumor type.
Methods:
We analyzed loss of heterozygosity (LOH) using a total of 50 markers on 20 chromosomal arms in 37 cases of microdissected CAC DNA.
Results:
LOH of >40% was observed on 2p (50%), 3p (45%), 9p (45%), 11q (46%), 17p (57%), 17q (44%), 18q (57%), and 19p (44%). LOH of 30-40% was observed on 6p (38%), 6q (40%), and 10q (31%). Overall, mean LOH was 34% and fractional allelic loss (FAL) was 0.34. High-level and low-level microsatellite instability (MSI) was shown in four cases (11%) and six cases (16%), respectively. Frequency of LOH on10q was significantly higher in endometrioid-type than endocervical-type adenocarcinoma (71% versus 20%; P < 0.05). Conversely, 6q LOH was higher in endocervical type than endometrioid type (0% versus 60%; P < 0.05). 19p13.3 has been reported to be frequently deleted in adenoma malignum, a histological subtype of CAC. To define the critical regions of LOH in CAC in general, we further performed deletion mapping of 19p using 13 markers. Unlike adenoma malignum, multiple regions on 19p appeared to be important loci of LOH for CAC.
Conclusion:
CACs develop with frequent LOH of multiple chromosomal arms, which may be related to its aggressive clinical behavior and poor prognosis. LOH of 10q may be unique to endometrioid-type CAC.
