Relationship of clone 4 estrogen receptor variant messenger RNA expression to some known prognostic variables in human breast cancer.
Relationship of clone 4 estrogen receptor variant messenger RNA expression to some known prognostic variables in human breast cancer.
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发表时间：
1995-02
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通讯作者：
L. Murphy;S. Hilsenbeck;Helmut Dotzlaw;S. Fuqua
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作者：
L. Murphy;S. Hilsenbeck;Helmut Dotzlaw;S. Fuqua
为了深入了解雌激素受体(ER)变异在乳腺癌中可能的生物学作用，我们开展了一项研究，以确定克隆4变异ER基因的表达是否与内分泌敏感性降低(即孕激素受体(PgR)阴性)或预后不良(结节阳性、肿瘤体积大、S期比例高)的标志物有关。应用核糖核酸酶保护法检测106例乳腺癌组织中克隆4变异型ER和野生型ER的mRNA水平。根据几个常规的生物学预后特征，肿瘤分为两大类：“良好”预后和“不良”预后。每组分为ER+/PGR+、ER+/PGR-和ER-/PGR-三个亚组。ER-/PGR-肿瘤中未检测到WT和Clone 4变异型ER mRNAs。我们确定克隆4变异ER mRNA水平与WT mRNA水平成比例变化，并用回归分析确定克隆4变异ER mRNA相对于WT的数量是否与预后或PGR含量有关。预后差的肿瘤克隆4变异体ER m RNA水平显著高于预后好的肿瘤(P=0.0004.0 5)。PGR-肿瘤中克隆4变异体ERmRNA的表达水平显著高于pGR+肿瘤(P=0.011)。这些数据与克隆4变异型ER mRNA的表达与人类乳腺癌从激素依赖到独立的进展相一致。
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.