Cyclin D1 (PRAD1) protein expression in breast cancer: approximately one-third of infiltrating mammary carcinomas show overexpression of the cyclin D1 oncogene.

Cyclin D1 (PRAD1) protein expression in breast cancer: approximately one-third of infiltrating mammary carcinomas show overexpression of the cyclin D1 oncogene.
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发表时间:
1995-06
期刊:
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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通讯作者:
L. Zukerberg;W. Yang;M. Gadd;A. Thor;F. Koerner;E. Schmidt;A. Arnold
L. Zukerberg;W. Yang;M. Gadd;A. Thor;F. Koerner;E. Schmidt;A. Arnold
中科院分区:
其他
文献类型:
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作者:
L. Zukerberg;W. Yang;M. Gadd;A. Thor;F. Koerner;E. Schmidt;A. Arnold

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在10-20%的乳腺癌和许多其他肿瘤(包括头颈部和食道的鳞状细胞癌)中观察到11q13染色体扩增;膀胱移行细胞癌;卵巢上皮性肿瘤。Cyclin D1/PRAD1可能是该扩增子的“驱动”基因,因为它在细胞周期控制中起作用,并且在具有11q13易位断点的甲状旁腺瘤和b细胞淋巴瘤中作为致癌基因被特别涉及。我们使用亲和纯化的细胞周期蛋白D1多克隆抗血清和微波/柠檬酸缓冲抗原检索系统检测了48例连续浸润性乳腺癌中细胞周期蛋白D1的表达。染色数据与临床病理特征、免疫印迹蛋白检测和11q13 DNA扩增相关。48例肿瘤中有17例(35%)可见明确的核染色(16例浸润性导管癌,以2/3级为主,1例浸润性小叶癌)。正常乳腺上皮、脂肪细胞、混合淋巴细胞未见核染色。cyclin D1过表达的肿瘤雌激素受体阳性(P < 0.005),孕激素受体阳性多见(P < 0.005),其他方面与研究组其他阴性病例相似。Western blot与免疫染色数据的相关性极好(P < 0.01)。22例中有5例经Western blot和免疫染色显示11q13 DNA扩增,cyclin D1蛋白水平升高。western blot和免疫组化结果显示,4例cyclin D1蛋白升高的患者未检测到11q13扩增。使用免疫组织化学技术对福尔马林固定的石蜡包埋组织,可以在大约三分之一的浸润性乳腺癌中检测到核周期蛋白D1蛋白。(摘要删节250字)
Amplification of chromosome 11q13 has been observed in 10-20% of breast carcinomas and numerous other tumors, including squamous cell carcinomas of the head, neck, and esophagus; transitional cell carcinomas of the urinary bladder; and epithelial ovarian tumors. Cyclin D1/PRAD1 is a likely "driver" gene for this amplicon because of its role in cell cycle control and because it has been specifically implicated as an oncogene in parathyroid adenomas and B-cell lymphomas with 11q13 translocation breakpoints. We examined cyclin D1 protein expression in 48 consecutive cases of infiltrating mammary carcinoma using an affinity-purified polyclonal antisera to cyclin D1 and a microwave/citrate buffer antigen retrieval system. Staining data were correlated with clinicopathological features, protein detection by immunoblots, and 11q13 DNA amplification. Definite nuclear staining was seen in 17/48 (35%) tumors (16 infiltrating ductal carcinomas, predominantly grade 2/3, and one infiltrating lobular carcinoma). There was no nuclear staining of normal breast epithelium, fat cells, or admixed lymphocytes. Tumors with overexpression of cyclin D1 were estrogen receptor-positive (P < .005) and usually progesterone receptor-positive (P < .005) but otherwise were similar to other negative cases in the study group. Correlation between Western blot and immunostaining data was excellent (P < .01). Five of the 22 cases studied showed 11q13 DNA amplification as well as increased levels of cyclin D1 protein by Western blot and immunostaining. Four cases with increased cyclin D1 protein by both western blots and immunohistochemistry did not have detectable 11q13 amplification. Nuclear cyclin D1 protein can be detected in approximately one-third of infiltrating breast carcinomas using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue.(ABSTRACT TRUNCATED AT 250 WORDS)