Michalides R, Hageman P, van Tinteren H, Houben L, Wientjens E, Klompmaker R, Peterse J
Department of Tumour Biology, The Netherlands Cancer Institute, Amsterdam.
Br J Cancer. 1996 Mar;73(6):728-34. doi: 10.1038/bjc.1996.128.
Overexpression of cyclin D1 is frequently found in various types of human tumours and results from clonal rearrangement and/or amplification involving chromosomal region 11q13. In order to evaluate the pathological relevance of cyclin D1 overexpression in human breast cancer, we generated a polyclonal antiserum against the carboxy-terminal part of the cyclin D1 protein. After affinity purification, the antiserum specifically detected overexpression of cyclin D1 in formalin-fixed, paraffin-embedded tumour material also. The intensity of the nuclear stainings was, in general, proportional to the degree of cyclin D1 amplification. We did not encounter significant variability of staining within individual tumours with overexpression of cyclin D1. Overexpression of cyclin D1 appeared to be associated with oestrogen receptor-positive breast tumours, but not with any other clinicopathological parameter tested. Overexpression of cyclin D1 was not prognostic value for recurrence of survival in a consecutive series of 248 operable breast cancer patients (stage I and II). Overexpression of p53 was also not of prognostic significance in this series, but was associated with undifferentiated histology and oestrogen receptor-negative breast tumours, as has been reported previously by others. A high proportion of breast tumours with a low grade of malignancy in this series of operable breast cancer patients may explain discrepancies concerning the prognostic value of amplification and of overexpression of cyclin D1.
细胞周期蛋白D1的过表达在各类人类肿瘤中经常被发现,它是由涉及染色体区域11q13的克隆重排和/或扩增导致的。为了评估细胞周期蛋白D1过表达在人类乳腺癌中的病理相关性,我们制备了一种针对细胞周期蛋白D1蛋白羧基末端部分的多克隆抗血清。经过亲和纯化后,该抗血清也能特异性检测福尔马林固定、石蜡包埋肿瘤组织中细胞周期蛋白D1的过表达。细胞核染色强度一般与细胞周期蛋白D1的扩增程度成正比。在细胞周期蛋白D1过表达的单个肿瘤内,我们未发现染色有显著差异。细胞周期蛋白D1的过表达似乎与雌激素受体阳性的乳腺肿瘤相关,但与所检测的任何其他临床病理参数无关。在连续的248例可手术乳腺癌患者(I期和II期)中,细胞周期蛋白D1的过表达对生存复发并无预后价值。在该系列中,p53的过表达也没有预后意义,但如之前其他人所报道的,它与未分化组织学和雌激素受体阴性的乳腺肿瘤相关。在这一系列可手术乳腺癌患者中,高比例的低恶性度乳腺肿瘤可能解释了关于细胞周期蛋白D1扩增和过表达的预后价值存在差异的原因。