Mesothelin gene expression and promoter methylation/hypomethylation in gynecological tumors.
OBJECTIVE
Mesothelin is a cell surface glycoprotein that is present on normal mesothelial cells and overexpressed in several cancers. In this study, we investigated the methylation/hypomethylation status in the promoter region of the mesothelin gene in gynecological tumors.


METHODS
Forty-four ovarian tumor specimens and 16 cases of uterine endometrial carcinoma, and normal tissue specimens were used. Monoclonal antibody (5B2) was employed for the immunohistochemical analysis. The methylation-sensitive single-nucleotide primer extension (Ms-SNuPE) technique was used to quantify the methylation/hypomethylation status at 20 CpG sites in the mesothelin promoter region.


RESULTS
Mesothelin was expressed in 100% of serous cystadenocarcinoma and 100% of serous borderline tumor of the ovary. None of the germ cell tumors and sexcord-stromal tumors was immunoreactive. Fifty percent of endometrial carcinoma was immunoreactive for mesothelin. The average methylation of CpG sites in ovarian tumors ranged from 6-56% (median: 31%) in mesothelin-positive and 13-79% (median: 43%) in mesothelin-negative samples. In endometrial tumors, the average methylation ranged from 5-52% (median: 28%) in mesothlin-positive and from 15-67% (median: 22%) in mesothlin-negative samples. A correlation was found between mesothelin expression and the average methylation/hypomethylation status as well as methylation/hypomethylation status at four of 20 CpG sites in ovarian samples. No correlation was found in endometrial samples.


CONCLUSIONS
We detected diverse levels of methylation/hypomethylation at CpG sites in the mesothelin promoter region in ovarian and endometrial tumors. We speculate that, although methylation/hypomethylation changes may affect its transcription, other mechanisms may synergically operate in tissue-specific expression and tumor-related mesothelin overexpression.
Obulhasim
G
G
Department of Pathology & Oncology, Juntendo University School of Medicine, Tokyo, Japan.
Fujii
H
H
Matsumoto
T
T
Yasen
M
M
Abe
M
M
Matsuoka
S
S
Ohtsuji
N
N
Hino
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D000090204:Mesothelin; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055815:Young Adult
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D000090204:Mesothelin