De Marchis L, Contegiacomo A, D'Amico C, Palmirotta R, Pizzi C, Ottini L, Mastranzo P, Figliolini M, Petrella G, Amanti C, Battista P, Bianco A R, Frati L, Cama A, Mariani-Costantini R
Departments of Experimental Medicine, University "La Sapienza," 00161 Rome.
Clin Cancer Res. 1997 Feb;3(2):241-8.
We analyzed 81 cases of primary breast carcinoma and 7 cases of fibroadenoma for microsatellite instability at eight loci. Twenty-seven cases (33.3%) manifested aberrant microsatellite alleles: 7 (8.6%) at one locus and 20 (24.7%) at two or more loci [tumors with replication error-positive (RER+) phenotype]. No evidence of microsatellite instability was observed in fibroadenomas. We investigated correlations between RER+ phenotype and clinicopathological characteristics of the carcinomas. The RER+ phenotype was statistically associated with large tumor diameter; of 19 RER+ tumors with measured size, 16 were > 2 cm, compared to 28 of 58 tumors with no evidence of microsatellite instability or with shifts in allele sizes limited to one locus (P </= 0.005, chi2 test). Consistently, there was also a strong statistical association between RER+ phenotype and lymph node metastasis; 14 of 19 RER+ tumors with known lymph node status were N+, compared to 15 of 59 tumors with no evidence of microsatellite instability or with allele shifts limited to one locus (P </= 0.0002, chi2 test). Correlations with age of patients, proliferative activity, histotype (ductal versus lobular), and grade of differentiation were not statistically significant, although the RER+ phenotype was more frequent in lobular and high-grade ductal carcinomas, in carcinomas with high proliferative activity, and in carcinomas from patients </=50 years. Data concerning cancer(s) in first and/or second degree relatives were available for 66 cases, including 33 positive and 33 negative for family history of cancer. No correlations were detected between RER+ phenotype and family history of cancer. In conclusion, our results indicate that in breast cancer, microsatellite instability is associated with clinicopathological parameters that are considered predictors of recurrent disease and aggressive behavior.
我们分析了81例原发性乳腺癌和7例纤维腺瘤在8个位点的微卫星不稳定性。27例（33.3%）表现出异常的微卫星等位基因：7例（8.6%）在一个位点，20例（24.7%）在两个或更多位点[具有复制错误阳性（RER+）表型的肿瘤]。在纤维腺瘤中未观察到微卫星不稳定性的证据。我们研究了RER+表型与癌的临床病理特征之间的相关性。RER+表型与肿瘤直径大在统计学上相关；在19例有测量大小的RER+肿瘤中，16例>2 cm，相比之下，58例无微卫星不稳定性证据或等位基因大小改变仅限于一个位点的肿瘤中有28例（P≤0.005，卡方检验）。同样，RER+表型与淋巴结转移之间也有很强的统计学关联；在19例已知淋巴结状态的RER+肿瘤中，14例为N+，相比之下，59例无微卫星不稳定性证据或等位基因改变仅限于一个位点的肿瘤中有15例（P≤0.0002，卡方检验）。与患者年龄、增殖活性、组织学类型（导管癌与小叶癌）和分化程度的相关性无统计学意义，尽管RER+表型在小叶癌和高级别导管癌、增殖活性高的癌以及50岁及以下患者的癌中更常见。66例患者有一级和/或二级亲属患癌的数据，其中33例有癌症家族史阳性，33例阴性。未检测到RER+表型与癌症家族史之间的相关性。总之，我们的结果表明，在乳腺癌中，微卫星不稳定性与被认为是复发疾病和侵袭性行为预测指标的临床病理参数相关。
