Thor Ann D, Eng Clarence, Devries Sandy, Paterakos Michael, Watkin William G, Edgerton Susan, Moore Dan H, Etzell Joan, Waldman Frederic M
Department of Pathology, University of Oklahoma Health Science Centers, Oklahoma City, USA.
Hum Pathol. 2002 Jun;33(6):628-31. doi: 10.1053/hupa.2002.124034.
Invasive micropapillary carcinoma (IMC) of the breast is a rare variant of invasive ductal carcinoma (IDC) characterized by unique histology and an extremely high incidence of lymph node metastases (approximately 95%). Comparative genomic hybridization (CGH) was used to characterize DNA extracted from 16 archival IMC cases to identify clonal genetic changes associated with this unique and highly metastatic cancer subtype. The average number of chromosomal alterations per IMC tumor was 7.4 +/-2.9 (3.4 gains and 3.9 losses), fewer than the number that we have observed in IDCs not otherwise specified (9.5 +/-6.6), IDCs with erbB-2 gene amplification (12.6 +/-5.9), and invasive lobular carcinomas (8.2 +/-5.5). The mean number of changes in IMC was significantly higher than we have observed in the rarely metastasizing tubular subtype of IDC (3.9 +/-2.3, P = 0.001), but less than the more aggressive subset of erbB-2-amplified IDC (P = 0.02). Remarkably, 100% of IMCs demonstrated loss involving the short arm of chromosome 8 (8p). Six cases showed loss of the entire 8p arm, whereas in 10 cases the loss was limited to the distal portion (8p21-pter) with localized gain of proximal 8p (8p11-p12). A reciprocal gain of 8q was detected in 14 cases (88%). Other common alterations included loss of 17p in 50% of tumors and loss of 16q in 50% of IMC cases. Gains of 17q (38%), 1q (31%), and 16p (25%) were also commonly detected. In comparison, IDCs (not otherwise specified), IDCs of the tubular subtype, and invasive lobular carcinomas showed only modest 8p loss (33%, 28%, and 13%, respectively). This region of chromosome 8 may contain 1 or more genes whose loss leads to this particular histology and/or the lymphotrophic phenotype associated with this histopathologic pattern.
乳腺浸润性微乳头状癌（IMC）是浸润性导管癌（IDC）的一种罕见变体，其特征在于独特的组织学表现和极高的淋巴结转移发生率（约95%）。采用比较基因组杂交（CGH）技术对16例存档IMC病例提取的DNA进行分析，以确定与这种独特的高转移性癌症亚型相关的克隆性基因改变。每例IMC肿瘤的染色体改变平均数为7.4±2.9（3.4处增益和3.9处缺失），少于我们在未另作说明的IDC（9.5±6.6）、erbB-2基因扩增的IDC（12.6±5.9）以及浸润性小叶癌（8.2±5.5）中观察到的数目。IMC的改变平均数显著高于我们在很少发生转移的IDC管状亚型中观察到的数目（3.9±2.3，P = 0.001），但低于erbB-2扩增的IDC中侵袭性更强的亚组（P = 0.02）。值得注意的是，100%的IMC显示8号染色体短臂（8p）缺失。6例显示整个8p臂缺失，而在10例中，缺失局限于远端部分（8p21 - pter），近端8p（8p11 - p12）有局部增益。在14例（88%）中检测到8q的相互增益。其他常见改变包括50%的肿瘤中17p缺失和50%的IMC病例中16q缺失。17q（38%）、1q（31%）和16p（25%）的增益也常见。相比之下，未另作说明的IDC、管状亚型的IDC和浸润性小叶癌仅显示适度的8p缺失（分别为33%、28%和13%）。8号染色体的这个区域可能包含1个或更多基因，其缺失导致了这种特定的组织学表现和/或与这种组织病理学模式相关的亲淋巴表型。
