Chen Yunn-Yi, Hwang Eun-Sil Shelley, Roy Ritu, DeVries Sandy, Anderson Joseph, Wa Chrystal, Fitzgibbons Patrick L, Jacobs Timothy W, MacGrogan Gaetan, Peterse Hans, Vincent-Salomon Anne, Tokuyasu Taku, Schnitt Stuart J, Waldman Frederic M
Department of Pathology, University of California San Francisco, California 94143, USA.
Am J Surg Pathol. 2009 Nov;33(11):1683-94. doi: 10.1097/PAS.0b013e3181b18a89.
The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.
多形性小叶原位癌（PLCIS）的临床、病理及分子特征，以及PLCIS与经典小叶原位癌（CLCIS）的关系尚未明确界定。在本研究中，我们分析了31例PLCIS（13例大汗腺型和18例非大汗腺型亚型），并将这些病例的临床、病理、免疫表型及基因特征与24例CLCIS的特征进行了比较。采用免疫染色法检测E-钙黏蛋白、乳腺囊肿病液蛋白-15、雌激素、孕激素、雄激素受体、人表皮生长因子受体2、细胞角蛋白5/6和Ki67的生物标志物表达。使用显微切割的福尔马林固定石蜡包埋样本进行基于芯片的比较基因组杂交，以评估基因组改变。PLCIS患者表现出乳腺钼靶异常。组织学上，肿瘤细胞黏附性差，核呈多形性，常伴有坏死和微钙化。所有病变的E-钙黏蛋白均为阴性。与CLCIS相比，PLCIS的Ki67指数显著更高，雌激素受体和孕激素受体表达更低，HER2基因扩增发生率更高。大多数PLCIS和CLCIS显示16号染色体长臂缺失和1号染色体获得。大汗腺型PLCIS的基因组改变明显多于CLCIS和非大汗腺型PLCIS。尽管E-钙黏蛋白表达缺失以及16号染色体长臂缺失和1号染色体获得的基于芯片的比较基因组杂交模式支持其与CLCIS的关系，但PLCIS具有将其与CLCIS区分开来的临床、乳腺钼靶、组织学、免疫表型和基因特征。在PLCIS中观察到的组织学特征、生物标志物谱和基因组不稳定性提示其表型比CLCIS更具侵袭性。然而，需要进行临床随访研究来确定这些病变的自然病程和最合适的处理方法。
