CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer.
CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer.
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发表时间：
1995-11
期刊：
影响因子：
11.2
通讯作者：
Kay Friedrichs;Folker E. Franke;Björn-Wieland Lisboa;G. Kügler;I. Gille;H. Terpe;F. Hölzel;
中科院分区：
文献类型：
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作者：
Kay Friedrichs;Folker E. Franke;Björn-Wieland Lisboa;G. Kügler;I. Gille;H. Terpe;F. Hölzel;
CD44是一种跨膜糖蛋白，存在于不同的细胞外区域。各种转录本由一个包含20个外显子的基因座编码，其中至少10个外显子可以在新生RNA中选择性剪接。由变异外显子编码的异构体（称为CD44v）在非恶性组织中的分布受到高度限制，这与许多组织中丰富的CD44的标准形式（CD44s）相反。含有外显子6v的特异性变异异构体已被证明可使非转移性大鼠肿瘤细胞转移。基于在大鼠转移形成中的突出作用，CD44v亚型被认为参与了人类肿瘤的进展。胃癌、结肠癌、非霍奇金淋巴瘤和乳腺癌的预后与CD44v表达的相关性已被报道。我们使用CD44v外显子特异性单克隆抗体，通过免疫组织化学方法评估了CD44亚型在淋巴结阳性（119例）和淋巴结阴性（108例）乳腺癌患者中的表达。在43例高危患者的子集中，使用逆转录- pcr来确定转录本的外显子组成。对蛋白和RNA表达数据进行统计学分析，探讨其与患者生存率及临床危险因素的相关性。与最近发表的数据（M. Kaufmann et al., Lancet, 345: 615-619, 1995）相反，在我们的队列中，在单变量和多变量分析中，无病和总生存数据未显示与所分析的同种异构体的表达有显著相关性。将CD44蛋白表达与肿瘤大小（pT1+pT2）和组织学分级等确定的临床生存危险因素进行比较，发现CD44蛋白表达与CD44s （P = 0.02和P = 0.03）和CD44-9v （P = 0.05）的存在相关。雌激素和孕激素受体水平升高的癌组织与CD44-6v呈正相关（P = 0.001），而雌激素受体阳性组织中CD44-9v和CD44-9v亚型的共表达趋势显著（P = 0.08和0.06）。在乳腺癌中，CD44s、CD44-9v和CD44-6v显然是细胞分化的标志，但不是肿瘤进展的标志。我们的数据表明，类固醇激素受体可能与人乳腺癌中含有cd44 -6v亚型的体内表达有关。
CD44 is a transmembrane glycoprotein occurring in several isoforms with different extracellular regions. The various transcripts are encoded by one gene locus containing 20 exons, of which at least 10 can be alternatively spliced in nascent RNA. Isoforms encoded by the variant exons (termed CD44v) are highly restricted in their distribution in nonmalignant tissue as opposed to the standard form of CD44 (CD44s) abundant in many tissues. Specific variant isoforms containing exon 6v have been shown to render nonmetastatic rat tumor cells metastatic. Based on the prominent role in rat metastasis formation, CD44v isoforms were suggested to be involved in human tumor progression. Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma. We evaluated the expression of CD44 isoforms in node-positive (n = 119) and node-negative (n = 108) cases of breast carcinoma by immunohistochemistry using CD44v exon-specific mAbs. In a subset of 43 cases of high-risk patients, reverse transcription-PCR was used to determine the exon composition of the transcripts. Protein and RNA expression data were probed statistically for their correlation to survival of the patients and clinical risk factors. In contrast to recently published data (M. Kaufmann et al., Lancet, 345: 615-619, 1995), in our cohort disease-free and overall survival data did not indicate significant correlations with the expression of the analyzed isoforms in univariate and multivariate analyses. Comparison of CD44 protein expression with established clinical risk factors for survival such as tumor size (pT1+pT2) and histological grading revealed correlations with the presence of CD44s (P = 0.02 and P = 0.03, respectively) and CD44-9v (P = 0.05 for histological grading). Carcinoma tissues with elevated estrogen and progesterone receptor levels showed positive correlation with CD44-6v (P = 0.001), while a trend for significant coexpression of CD44s and CD44-9v isoforms was observed in estrogen receptor-positive tissues (P = 0.08 and 0.06, respectively). In breast cancer, CD44s, CD44-9v, and CD44-6v are apparently markers for cellular differentiation but not for tumor progression. Our data suggest that steroid hormone receptors may be associated with the in vivo expression of CD44-6v-containing isoforms in human mammary carcinoma.