Loss of heterozygosity at 11q22 correlates with low progesterone receptor content in epithelial ovarian cancer.
Forty-seven epithelial ovarian cancers were analyzed for loss of heterozygosity (LOH) at D11S35 (11q22), close to the progesterone receptor (PR) gene, and for tumoral estrogen receptor (ER) and PR content. Thirty-eight of 47 tumors were informative, and, of these, 14 exhibited LOH. There was a significant association (P = 0.014) between D11S35 LOH and low tumoral PR content. For all informative tumors, there was no correlation between ER and PR; however, exclusion of tumors with LOH from the informative series revealed a linear correlation between tumoral ER and PR (P = 0.013), and established ER (P = 0.025) and PR (P = 0.05) content as significant factors in relation to patient survival. Patients with ER-rich tumors with D11S35 LOH had particularly poor survival compared with ER-rich, D11S35 heterozygous, no loss patients (P = 0.014). Analysis of the same tumors using two other microsatellites, D11S935 (11p13) and NM23 (17q22), showed no statistically significant relationships, although there were nonsignificant trends for the correlation of ER and PR expression in informative tumors without allele loss at these loci. We propose that genomic structural alteration at or close to the PR gene locus has biological and clinical sequelae in ovarian cancer.
Gabra
H
H
Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU.
Langdon
S P
SP
Watson
J E
JE
Hawkins
R A
RA
Cohen
B B
BB
Taylor
L
L
Mackay
J
J
Steel
C M
CM
Leonard
R C
RC
Smyth
J F
JF
D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis* / Q000235:genetics; D016019:Survival Analysis
D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone