Marchiò C, Iravani M, Natrajan R, Lambros M B, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Di Palma S, Schmitt F C, Bussolati G, Ellis L O, Ashworth A, Sapino A, Reis-Filho J S
The Breakthrough Breast Cancer Research Centre--Institute of Cancer Research, London, UK.
J Pathol. 2008 Aug;215(4):398-410. doi: 10.1002/path.2368.
Pure invasive micropapillary carcinoma (MPC) is a special histological type that accounts for 0.7-3% of all breast cancers. MPC has a distinctive growth pattern and a more aggressive clinical behaviour than invasive ductal carcinomas of no special type (IDC-NSTs). To define the molecular characteristics of MPCs, we profiled a series of 12 MPCs and 24 grade and oestrogen receptor (ER)-matched IDC-NSTs using high-resolution microarray comparative genomic hybridization (aCGH). In addition, we generated a tissue microarray containing a series of 24 MPCs and performed immunohistochemical analysis with ER, PR, Ki-67, HER2, CK5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1, E-cadherin, and beta-catenin antibodies. In situ hybridization probes were employed to evaluate the prevalence of amplification of HER2, TOP2A, EGFR, CCND1, MYC, ESR1, and FGFR1 genes. aCGH analysis demonstrated that MPCs significantly differed from IDC-NSTs at the genomic level. Gains of 1q, 2q, 4p, 6p, 6q23.2-q27, 7p, 7q, 8p, 8q, 9p, 10p, 11q, 12p, 12q, 16p, 17p, 17q, 19p, 20p, 20q, and 21q, and losses of 1p, 2p, 6q11.1-q16.3, 6q21-q22.1, 9p, 11p, 15q, and 19q were more prevalent in MPCs. High-level gains/amplifications of 8p12-p11, 8q12, 8q13, 8q21, 8q23, 8q24, 17q21, 17q23, and 20q13 were significantly associated with MPCs. A comparison between 24 MPCs and a series of 48 grade and ER-matched IDC-NSTs revealed that high cyclin D1 expression, high proliferation rates, and MYC (8q24) amplification were significantly associated with MPCs. Our results demonstrate that MPCs have distinct histological features and molecular genetic profiles supporting the contention that they constitute a distinct pathological entity.
纯侵袭性微乳头癌（MPC）是一种特殊的组织学类型，占所有乳腺癌的0.7%-3%。与非特殊类型的浸润性导管癌（IDC-NST）相比，MPC具有独特的生长模式和更具侵袭性的临床行为。为了明确MPC的分子特征，我们使用高分辨率微阵列比较基因组杂交（aCGH）对12例MPC和24例分级及雌激素受体（ER）匹配的IDC-NST进行了分析。此外，我们制作了一个包含24例MPC的组织微阵列，并用ER、PR、Ki-67、HER2、CK5/6、CK14、CK17、EGFR、拓扑异构酶-IIα、细胞周期蛋白D1、小窝蛋白-1、E-钙黏蛋白和β-连环蛋白抗体进行了免疫组化分析。采用原位杂交探针评估HER2、TOP2A、EGFR、CCND1、MYC、ESR1和FGFR1基因扩增的发生率。aCGH分析表明，MPC在基因组水平上与IDC-NST有显著差异。1q、2q、4p、6p、6q23.2-q27、7p、7q、8p、8q、9p、10p、11q、12p、12q、16p、17p、17q、19p、20p、20q和21q的增益以及1p、2p、6q11.1-q16.3、6q21-q22.1、9p、11p、15q和19q的缺失在MPC中更为常见。8p12-p11、8q12、8q13、8q21、8q2b、8q24、17q21、17q23和20q13的高水平增益/扩增与MPC显著相关。对24例MPC和48例分级及ER匹配的IDC-NST进行比较发现，细胞周期蛋白D1高表达、高增殖率和MYC（8q24）扩增与MPC显著相关。我们的结果表明，MPC具有独特的组织学特征和分子遗传学特征，支持它们构成一个独特病理实体的观点。
