Incidence of chromosomes 1 and 17 aneusomy in breast cancer and adjacent tissue: An interphase cytogenetic study
Incidence of chromosomes 1 and 17 aneusomy in breast cancer and adjacent tissue: An interphase cytogenetic study
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DOI：
10.1016/s1072-7515(00)00252-0
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发表时间：
2000-05-01
影响因子：
5.2
通讯作者：
Cianciulli, AM
中科院分区：
文献类型：
--
作者：
Botti, C;Pescatore, B;Cianciulli, AM
背景：对乳腺癌发生早期阶段潜在的生物病理事件进行特征描述，可能会对降低乳腺癌死亡率产生重大影响。参与乳腺肿瘤发生的基因位于1号和17号染色体上，这些染色体的数目异常与乳腺癌的发生和进展相关。根据区域癌变假说，特定的染色体异常可能存在于乳腺癌以及外观正常的邻近组织中。后一种变化反映了长期致癌暴露后的基因组损伤，且发生在形态学可检测到的肿瘤转化之前。我们假设检测良性乳腺上皮中的这些异常可能为分子风险评估提供一种工具。
研究设计：我们使用着丝粒特异性探针进行荧光原位杂交，测定了28例原发性肿瘤样本和54例取自乳腺癌手术患者的周围未受累实质样本的新鲜印片上1号和17号染色体的状态。还评估了10例取自既往患有乳腺癌患者的对侧乳腺活检标本，作为高危组的替代样本，以排除肿瘤邻近组织中的染色体非整倍性可能与原发性肿瘤的旁分泌效应相关这一假设。使用10例取自低风险患者的良性乳腺组织样本作为对照，以确定非整倍性定义的耐受限度。
结果：使用40%的信号丢失和13%的信号增加作为定义染色体非整倍性的阈值（即对照组信号的平均值±3倍标准差），我们发现：1）几乎所有原发性乳腺癌在1号和17号染色体上均为非整倍体；2）在66.7%的患者中，原发性乳腺癌和邻近的未受累实质在1号和17号染色体非整倍性上具有相同模式；3）高危患者对侧良性乳腺样本中的1号和17号染色体非整倍性与原发性乳腺癌或邻近组织样本中的情况无差异。
结论：这些结果表明，1号和17号染色体非整倍性可能是乳腺肿瘤发生的一种中间生物标志物，可能有助于检测出可能从预防性干预中获益的乳腺癌高危患者。（《美国细胞外科学杂志》2000年；130：530 - 539。美国外科医师学会2000年版权所有）
Background: Characterization of the biopathologic events underlying the early steps of breast carcinogenesis may have a dramatic impact on reducing breast cancer mortality. Genes involved in breast tumorigenesis are localized on chromosomes 1 and 17, and numeric aberrations of these chromosomes have been correlated with breast cancer tumorigenesis and progression. According to the field cancerization hypothesis, specific chromosome aberrations may be present in breast cancer and in normal-appearing adjacent tissue. The latter changes reflect the genomic damage that follows longterm carcinogenic exposure and precede the morphologically detectable neoplastic transformation. We hypothesize that detection of these aberrations in benign breast epithelium may provide a tool for molecular risk assessment.Study Design: Using fluorescence in situ hybridization with centromere-specific probes, we determined the status of chromosomes 1 and 17 in fresh imprints of 28 samples of primary tumors and 54 samples of their surrounding uninvolved parenchyma taken from patients undergoing operations for breast carcinoma. Ten contralateral breast biopsy specimens collected from patients with previous breast carcinoma were also evaluated as a surrogate of a high-risk group to rule out the hypothesis that chromosomal aneusomy in tumor-adjacent tissue could be related to a paracrine effect of the primary tumor Ten samples of benign breast tissue taken from patients at low risk were used as controls to define tolerance limits for aneusomy definition.Results: Using threshold values of 40% of signal loss and 13% of signal gain to define chromosome aneusomy tie, mean + 3 SDs of the control group signals), we found the following: 1) almost all primary breast tumors were aneusomic for chromosomes 1 and 17; 2) primary breast tumor and adjacent uninvolved parenchyma shared the same pattern of chromosomes 1 and 17 aneusomy in 66.7% of patients; and 3) chromosomes 1 and 17 aneusomies in contralateral benign breast samples from high-risk patients were not different from those in primary breast tumor or adjacent tissue samples.Conclusions: These results suggest that chromosomes 1 and 17 aneusomy may represent an intermediate biomarker of breast tumorigenesis potentially useful to detect patients at high risk of breast carcinoma who may benefit from preventive interventions. (J Am Cell Surg 2000;130:530-539. (C) 2000 by the American College of Surgeons).