title: Relationship of clone 4 estrogen receptor variant messenger RNA expression to some known prognostic variables in human breast cancer.
abstract: To gain insight into the possible biological role of variant estrogen receptor (ER) expression in human breast cancer, we have undertaken a study to determine if the expression of the clone 4 variant ER mRNA was associated with markers of either reduced endocrine sensitivity [i.e., progesterone receptor (PgR) negativity] or a poor prognosis (node positivity, large tumor size, and high percentage S-phase fraction). mRNA levels of clone 4 variant ER and wild-type (WT) ER were assayed by RNase protection assay in 106 breast cancer specimens. The tumors comprised two major groups: "good" prognosis and "poor" prognosis based on several conventional biological prognostic features. Each group was divided into three subgroups (ER+/PgR+, ER+/PgR-, and ER-/PgR-). WT and clone 4 variant ER mRNAs were undetected in ER-/PgR- tumors. We determined that clone 4 variant ER mRNA levels varied proportionately with WT mRNA levels, and regression analysis was used to determine if the amount of clone 4 variant ER mRNA relative to WT was associated with prognosis or PgR content. Significantly higher levels of clone 4 variant ER mRNA relative to WT were found in tumors with markers of poor prognosis compared to those with markers of good prognosis (P = 0.0004). Significantly higher levels of clone 4 variant ER mRNA relative to WT were found in PgR- tumors compared to PgR+ tumors (P = 0.011). Such data are consistent with an association of clone 4 variant ER mRNA expression with progression of human breast cancer from hormone dependence to independence.
authors.affiliation: Department of Biochemistry, University of Manitoba, Winnipeg, Manitoba, R3E 0W3, Canada.
authors.forename: L C
authors.initials: LC
authors.lastname: Murphy
authors.forename: S G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: H
authors.initials: H
authors.lastname: Dotzlaw
authors.forename: S A
authors.initials: SA
authors.lastname: Fuqua
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D003001:Cloning, Molecular; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000032:analysis; D012044:Regression Analysis; D016196:S Phase; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone