Expression of oestrogen receptor alpha variants in non-malignant breast and early invasive breast carcinomas.
Oestrogen receptor (ER) alpha variants have been described in normal breast and breast carcinomas, but their presence in a range of benign conditions and in small early invasive breast carcinomas has not been considered. Cryostat tissue sections from 19 normal and proliferative breast lesions and 44 carcinomas 15 mm and less in size detected by mammographic screening were screened for ERalpha splice variants using reverse transcriptase-nested PCR. The carcinomas were assessed for mutation by single-stranded conformational polymorphism analysis and variant forms/band shifts were sequenced. ERalpha was detected in all 19 non-malignant cases and exon 7-deleted variants were found in 16 of them. Three cases showed weak expression of exon 5, and two of exon 3 variants. There was no relationship between the presence of variants and the extent of proliferative change, ER status or age. ERalpha mRNA was not detected in two carcinomas; exon 3 deletions were found in four (9. 5%) of the other carcinomas, exon 5 in two (4.8%), and exon 7 in 11 (26.2%), with two variants in four carcinomas and a total of 29.5% of all cases having detectable variants. Two point mutations were found in one, which was a tubular carcinoma. Variant forms were identified in carcinomas of all sizes (bar<10 mm) but were more frequent in those of 15 mm. There was no relationship with type, grade or receptor status. The main difference between non-malignant breast and early invasive cancers related to exons 3 and 5. The findings suggest that ERalpha variants are not involved in breast cancer development but occur with tumour progression and may be a consequence rather than a cause.
Chappell
S A
SA
The Scripps Research Institute, Department of Neurobiology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Johnson
S M
SM
Shaw
J A
JA
Walker
R A
RA
D000328:Adult; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D005348:Fibrocystic Breast Disease / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen