Watters A D, Going J J, Cooke T G, Bartlett J M S
University Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland, UK.
Breast Cancer Res Treat. 2003 Jan;77(2):109-14. doi: 10.1023/a:1021399923825.
Aberrations of chromosome 17 are common in breast cancer. Fluorescence in situ hybridization (FISH) enables gene or chromosome copy number to be assessed in situ in archival tissues and related to morphology and clinical outcome. In this study direct labeled DNA probes for the chromosome 17 alpha satellite and the HER2/neu gene were applied simultaneously to 5 micron sections of 214 formalin-fixed paraffin-embedded invasive primary breast carcinomas. A high proportion (54%) of invasive breast carcinomas displayed aneusomy of chromosome 17. Polysomy 17 correlated with multiple copies of HER2/neu (p = < 0.001), but not with HER2/neu amplification. Eighty-six patients without HER2/neu amplification had aneusomy 17. Fifty-eight of the 86 patients that had aneusomy 17 had high HER2/neu copy number. Twelve patients with normal copy number for chromosome 17 had amplification of HER2/neu and 30 patients had amplification of HER2/neu with aneusomy 17. Aneusomy 17 was associated with grade 3 carcinoma (p = 0.008), ER negativity (p = 0.0032) and a Nottingham prognostic index of greater than 5.4 (p = 0.039) but was not associated with survival by univariate analysis. In conclusion, the determination of chromosome 17 copy number should be incorporated in assessment of HER2/neu status, as this will give an accurate measure of amplification of HER2/neu and may also be helpful in determining suitability for breast carcinoma trials.
17号染色体畸变在乳腺癌中很常见。荧光原位杂交(FISH)能够在存档组织中原位评估基因或染色体的拷贝数,并将其与形态学和临床结果相关联。在本研究中,将针对17号染色体α卫星和HER2/neu基因的直接标记DNA探针同时应用于214例福尔马林固定石蜡包埋的浸润性原发性乳腺癌的5微米切片。高比例(54%)的浸润性乳腺癌显示17号染色体非整倍体。17号染色体多体性与HER2/neu的多个拷贝相关(p = < 0.001),但与HER2/neu扩增无关。86例无HER2/neu扩增的患者存在17号染色体非整倍体。86例有17号染色体非整倍体的患者中有58例HER2/neu拷贝数高。12例17号染色体拷贝数正常的患者有HER2/neu扩增,30例有HER2/neu扩增且伴有17号染色体非整倍体。17号染色体非整倍体与3级癌(p = 0.008)、雌激素受体阴性(p = 0.0032)和诺丁汉预后指数大于5.4(p = 0.039)相关,但单因素分析显示与生存率无关。总之,17号染色体拷贝数的测定应纳入HER2/neu状态的评估中,因为这将准确衡量HER2/neu的扩增情况,也可能有助于确定是否适合进行乳腺癌试验。