[Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers].

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.目的： 探讨人表皮生长因子受体2(HER-2)瘤内异质性乳腺癌的病理学特征，及肿瘤免疫微环境与HER-2瘤内异质性的关系。 方法： 2017年11月至2020年6月天津医科大学肿瘤医院收治的HER-2瘤内异质性乳腺癌30例，采用免疫组化技术(IHC)检测肿瘤组织中HER-2的表达，采用双色银染原位杂交技术(D-SISH)验证HER-2的状态，划分瘤内HER-2阳性区域和阴性区域，分别评估病理学特征、分子分型以及肿瘤浸润淋巴细胞(TILs)和程序性死亡蛋白配体1(PD-L1)的表达。 结果： 30例HER-2瘤内异质性乳腺癌中，HER-2阳性细胞百分比为10%~90%。病理类型以非特殊类型浸润性癌为主，其中6例患者HER-2阳性区域与阴性区域的病理类型不同，HER-2阳性区域2例病理类型为特殊类型的患者均为大汗腺癌，HER-2阴性区域4例病理类型为特殊类型的患者包括2例浸润性微乳头状癌，1例浸润性乳头状癌，1例大汗腺癌。HER-2阳性区域腔上皮B型17例，HER-2过表达型13例；HER-2阴性区域腔上皮B型22例，三阴性型8例。HER-2阳性区域和阴性区域中TILs高水平的患者分别占53.3%(16/30)和26.7%(8/30)，差异有统计学意义(P＝0.035)。HER-2阳性区域和HER-2阴性区域PD-L1表达阳性者分别为6例和9例。8例HER-2阴性区域含三阴性成分的乳腺癌中，4例PD-L1表达阳性。 结论： 针对HER-2瘤内异质性乳腺癌，病理医师需要同时关注HER-2阳性区域和阴性区域，并尽可能分别评估分子分型。对于含有三阴性成分的HER-2瘤内异质性乳腺癌，可通过细化PD-L1的瘤内表达情况优化治疗方式。.