Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Department of Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Ann Diagn Pathol. 2023 Aug;65:152150. doi: 10.1016/j.anndiagpath.2023.152150. Epub 2023 Apr 23.
Uterine carcinosarcoma (UCS) frequently expresses human epidermal growth factor receptor 2 (HER2) and metastasizes. However, little is known about changes in the HER2 expression status in metastatic lesions and its impact on clinical outcomes. In 41 patients with synchronous or metachronous metastases and matched primary UCSs, we assessed the HER-2 expression using immunohistochemistry and scored it per the 2016 American Society of Clinical Oncology/College of American Pathologists guidelines, modified for UCS. We compared HER2 scores between paired primary and metastatic lesions and reviewed the association between clinicopathological characteristics and impact on overall survival. HER2 scores of 3+, 2+, 1+, and 0 were observed in 12.2 %, 34.2 %, 26.8 %, and 26.8 % of primary tumors, respectively, and 9.8 %, 19.5 %, 43.9 %, and 26.8 % of metastatic tumors, respectively. HER2 intratumoral heterogeneity occurred in 46.3 % and 19.5 % of the primary and metastatic lesions, respectively. The agreement rate of the HER2 score was 34.2 % in the four-tiered scale, while it was 70.7 % in the two-tiered scale (score 0 vs. score ≥ 1+) with fair agreement (к = 0.26). Patients with HER2 discordance showed significantly shorter overall survival (hazard ratios = 2.38, 95 % confidence interval 1.01-5.5, p = 0.049). HER2 discordance was not associated with specific clinicopathological characteristics. Discordance in HER2 status between primary and metastatic tumors in UCS was frequently observed regardless of clinicopathological characteristics and was a poor prognostic factor. Even if one tumor (primary or metastatic) is HER2 negative, HER2 testing of other tumors may be beneficial in terms of patient treatment options.
子宫癌肉瘤（UCS）常表达人类表皮生长因子受体 2（HER2）并发生转移。然而，对于转移性病变中 HER2 表达状态的变化及其对临床结局的影响知之甚少。在 41 例同步或异时转移且配对的原发性 UCS 患者中，我们使用免疫组织化学法评估了 HER-2 的表达，并按照 2016 年美国临床肿瘤学会/美国病理学家学院指南进行评分，该评分针对 UCS 进行了修改。我们比较了配对原发性和转移性病变之间的 HER2 评分，并回顾了临床病理特征与总生存的相关性。原发性肿瘤中分别有 12.2%、34.2%、26.8%和 26.8%的肿瘤 HER2 评分分别为 3+、2+、1+和 0，而转移性肿瘤中分别为 9.8%、19.5%、43.9%和 26.8%。原发性和转移性病变中分别有 46.3%和 19.5%的肿瘤存在 HER2 肿瘤内异质性。在四级评分中，HER2 评分的一致性率为 34.2%，而在二级评分（评分 0 与评分≥1+）中，一致性率为 70.7%，一致性一般（к=0.26）。HER2 不一致的患者总生存率明显较短（风险比=2.38，95%置信区间 1.01-5.5，p=0.049）。HER2 不一致与特定的临床病理特征无关。在 UCS 中，无论临床病理特征如何，原发性和转移性肿瘤之间的 HER2 状态不一致经常发生，并且是预后不良的因素。即使一个肿瘤（原发性或转移性）HER2 阴性，对其他肿瘤进行 HER2 检测在患者治疗选择方面可能也是有益的。
