Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
Hum Pathol. 2018 Jul;77:63-69. doi: 10.1016/j.humpath.2018.03.015. Epub 2018 Mar 27.
Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. MPUC has been shown to commonly exhibit ERBB2 amplification and HER2 protein overexpression, but the frequency and distribution of these findings within micropapillary (MP) and not otherwise specified (NOS) components of tumors with mixed histology have not been addressed. Therefore, we evaluated ERBB2 amplification and HER2 expression in 43 MPUC cases by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Of the 35 tumors containing both MP and NOS components, ERBB2 amplification was present in both the MP and NOS components of 12 tumors (34.3%), in only the MP component of 11 tumors (31.4%), and exclusively in the NOS component of 4 tumors (11.4%). HER2 protein overexpression was significantly more commonly present in the MP component compared to the NOS component within the same tumor (68.6% versus 34.3%, P = .012). Overall, there was a moderately positive correlation between HER2 protein expression and ERBB2 amplification in both MP (ρ = 0.59, P < .001) and NOS (ρ = 0.70, P < .001) components. All MP/NOS areas with IHC score 3+ and none of MP/NOS areas with IHC score 0 were associated with ERBB2 amplification. We conclude that ERBB2 amplification and HER2 overexpression are preferentially but not exclusively identified in the MP component compared to the NOS component within the same tumor. Our findings identify the presence of intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC and provide grounds for further investigation into the mechanisms underlying the development of MPUC.
微乳头状尿路上皮癌（MPUC）是一种罕见但侵袭性较强的尿路上皮癌变异型。MPUC 常表现为 ERBB2 扩增和 HER2 蛋白过表达，但在混合组织学肿瘤的微乳头状（MP）和非特指（NOS）成分中，这些发现的频率和分布尚未得到解决。因此，我们通过荧光原位杂交（FISH）和免疫组织化学（IHC）评估了 43 例 MPUC 病例中 ERBB2 扩增和 HER2 表达。在包含 MP 和 NOS 成分的 35 例肿瘤中，有 12 例（34.3%）肿瘤的 MP 和 NOS 成分均存在 ERBB2 扩增，11 例（31.4%）肿瘤仅在 MP 成分中存在，4 例（11.4%）肿瘤仅在 NOS 成分中存在。HER2 蛋白过表达在同一肿瘤的 MP 成分中明显比 NOS 成分更为常见（68.6%比 34.3%，P =.012）。总体而言，在 MP（ρ=0.59，P <.001）和 NOS（ρ=0.70，P <.001）成分中，HER2 蛋白表达与 ERBB2 扩增之间存在中度正相关。所有 IHC 评分 3+的 MP/NOS 区域均与 ERBB2 扩增相关，而 IHC 评分 0 的 MP/NOS 区域均与 ERBB2 扩增无关。我们得出结论，与同一肿瘤的 NOS 成分相比，ERBB2 扩增和 HER2 过表达优先但并非仅在 MP 成分中被识别。我们的发现确定了 MPUC 中 ERBB2 扩增和 HER2 表达的肿瘤内异质性的存在，并为进一步研究 MPUC 发生的机制提供了依据。
