Naidu Rakesh, Wahab Norhanom Abdul, Yadav Man Mohan, Kutty Methil Kannan
International Medical University, Sesama Centre, Plaza Komenwel, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
Oncol Rep. 2002 Mar-Apr;9(2):409-16.
Overexpression and amplification of cyclin D1 were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues. Overexpression of cyclin D1 was detected in 60% (263/440) and amplification of cyclin D1 was noted in 27% (119/440) of the primary breast carcinomas. Molecular analysis demonstrated that cyclin D1 was amplified in 30% (7/23) of the comedo DCIS, 22% (9/41) of the comedo DCIS and 32% (13/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 27% (9/33) of the invasive lobular carcinomas, 19% (4/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. Cyclin D1 was amplified in 11% (2/19) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. Our observation showed that cyclin D1 was strongly positive in 61% (14/23) of the comedo subtype, 61% (11/18) of the non-comedo subtype, 59% (24/41) of the comedo DCIS and 63% (26/41) of the adjacent invasive ductal carcinomas, 53% (10/19) of the non-comedo DCIS and 58% (11/19) of the adjacent invasive lesions, 58% (157/270) of the invasive ductal carcinomas, 73% (24/33) of the invasive lobular carcinomas, 52% (11/21) of the colloid carcinomas and 27% (4/15) of the medullary carcinomas. A significant association was observed between in situ components and adjacent invasive lesions for cyclin D1 expression (p<0.05) and amplification (p<0.05). A significant relationship was noted between amplification of cyclin D1 and lymph node metastases (p<0.05) but not with histological grade (p>0.05), estrogen receptor status (p>0.05) and proliferation index (Ki-67 and PCNA) (p>0.05). However, overexpression of cyclin D1 was statistically associated with well differentiated tumors (p<0.05) and estrogen receptor positivity (p<0.05). No relationship was seen with nodal status (p>0.05) and proliferation index (Ki-67 and PCNA) (p>0.05). These observations suggest that tumors positive for cyclin D1 protein may have features of good prognosis but amplification of cyclin D1 gene could be an indicator of tumors with poor prognostic features. Although majority of the Malaysian patients belong to younger age group (<50 years old), amplification and expression of cyclin D1 was not statistically associated with patient age (p>0.05). These observations indicate that amplification and up-regulation of cyclin D1 may be independent of patient age. Moreover, overexpression and amplification of cyclin D1 in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that the gene may play an important role in early and late stages of breast carcinogenesis.
采用免疫组织化学和差异聚合酶链反应（dPCR）对440例福尔马林固定的原发性乳腺癌组织进行细胞周期蛋白D1过表达和扩增情况的研究。在原发性乳腺癌中，60%（263/440）检测到细胞周期蛋白D1过表达，27%（119/440）发现细胞周期蛋白D1扩增。分子分析表明，粉刺型导管原位癌（DCIS）中30%（7/23）、非粉刺型DCIS中22%（9/41）、相邻浸润性导管癌中32%（13/41）、浸润性导管癌中30%（82/270）、浸润性小叶癌中27%（9/33）、黏液癌中19%（4/21）、髓样癌中13%（2/15）存在细胞周期蛋白D1扩增。在11%（2/19）的浸润性导管癌中检测到细胞周期蛋白D1扩增，但在相邻的非粉刺型DCIS病变中未检测到。我们的观察显示，粉刺型亚型中61%（14/23）、非粉刺型亚型中61%（11/18）、粉刺型DCIS中59%（24/41）、相邻浸润性导管癌中63%（26/41）、非粉刺型DCIS中53%（10/19）、相邻浸润性病变中58%（11/19）、浸润性导管癌中58%（157/270）、浸润性小叶癌中73%（24/33）、黏液癌中52%（11/21）、髓样癌中27%（4/15）的细胞周期蛋白D1呈强阳性。细胞周期蛋白D1表达（p<0.05）和扩增（p<0.05）在原位成分与相邻浸润性病变之间存在显著相关性。细胞周期蛋白D1扩增与淋巴结转移之间存在显著相关性（p<0.05），但与组织学分级（p>0.05）、雌激素受体状态（p>0.05）和增殖指数（Ki-67和PCNA）（p>0.05）无关。然而，细胞周期蛋白D1过表达与高分化肿瘤（p<0.05）和雌激素受体阳性（p<0.05）在统计学上相关。与淋巴结状态（p>0.05）和增殖指数（Ki-67和PCNA）（p>0.05）无相关性。这些观察结果表明，细胞周期蛋白D1蛋白阳性的肿瘤可能具有预后良好的特征，但细胞周期蛋白D1基因扩增可能是预后不良肿瘤的一个指标。尽管大多数马来西亚患者属于较年轻年龄组（<50岁），但细胞周期蛋白D1的扩增和表达与患者年龄在统计学上无相关性（p>0.05）。这些观察结果表明，细胞周期蛋白D1的扩增和上调可能与患者年龄无关。此外，细胞周期蛋白D1在原位、原位和相邻浸润性病变以及浸润性癌中的过表达和扩增表明，该基因可能在乳腺癌发生的早期和晚期阶段发挥重要作用。
