Department of Pathology, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 4 rue de la Chine, 75020, Paris, France.
Department of Urology, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France.
Virchows Arch. 2021 Apr;478(4):637-645. doi: 10.1007/s00428-020-02951-0. Epub 2020 Oct 30.
Urothelial carcinoma of the bladder (UC) has a poor prognosis, partly because of chemotherapy resistance. Molecular classifications have shown their interest and can help to offer personalized treatment. In this study, we evaluated the feasibility of an immunohistochemical study to divide advanced UC into clinico-pathological-molecular subgroups and evaluate phenotypic correspondence between primary UC and matched lymph node metastases (LMN). An eight-antibody immunohistochemical panel was performed on UC and matched LMN from patients treated with radical cystectomy. One hundred eighty-seven UCs (100 pN0 tumor and 87 pN+ tumor) were tested. Multiple correspondence analysis showed that UC expressing GATA3 also expressed FOXA1 (p = 0.010) and did not stain for CK5/6 (p = 0.031) nor CK14 (p = 0.003). UC expressing CK14 coexpressed CK5/6 (p < 0.0001), had high Ki67 (p = 0.010) and no GATA3 (p = 0.003) nor FOXA1 (p = 0.011) expression. Loss of expression of STAG2 was associated with high Ki67 (p = 0.001). Sixty-seven percent of [CK5/6 CK14]+ [GATA3 FOAXA1]- patients had high Ki67 expression vs 37% of [GATA3 FOXA1]+ [CK5/6 CK14]- patients (p = 0.024). The majority of [CK5/6 CK14]+ [GATA3 FOAXA1]- patients (92%) had advanced disease (pT3-pT4) whilst 86% of pT1-T2 cases were [GATA3 FOXA1]+ [CK5/6 CK14]- (p = 0.041). Differential antigen expression between 63 pN+ primary tumors and their corresponding LNM showed the following concordance percentages: p53 (76%), p63 (75%), CK5/6 (65%), CK14 (89%), GATA3 (75%), FOXA1 (68%), STAG2 (65%), and Ki-67 (71%). These results support the interest of immunohistochemistry for subtype profiling in metastatic UC, using CK5/6, CK14, GATA3, and FOXA1, highlighting also few phenotypical modifications when tumor spreads to lymph nodes.
膀胱尿路上皮癌（UC）预后较差，部分原因是化疗耐药。分子分类已经显示出它们的兴趣，并有助于提供个性化治疗。在这项研究中，我们评估了免疫组织化学研究将晚期 UC 分为临床病理分子亚组的可行性，并评估了原发性 UC 与匹配的淋巴结转移（LMN）之间的表型对应关系。对接受根治性膀胱切除术治疗的患者的 UC 和匹配的 LMN 进行了八种抗体免疫组织化学检测。对 187 例 UC（100 例 pN0 肿瘤和 87 例 pN+肿瘤）进行了检测。多对应分析显示，表达 GATA3 的 UC 也表达 FOXA1（p=0.010），不染色 CK5/6（p=0.031）或 CK14（p=0.003）。表达 CK14 的 UC 共表达 CK5/6（p<0.0001），Ki67 高（p=0.010），无 GATA3（p=0.003）和 FOXA1（p=0.011）表达。STAG2 表达缺失与 Ki67 高（p=0.001）相关。[CK5/6 CK14]+[GATA3 FOAXA1]-患者中有 67%的患者 Ki67 高表达，而[GATA3 FOAXA1]+[CK5/6 CK14]-患者中有 37%的患者 Ki67 高表达（p=0.024）。大多数[CK5/6 CK14]+[GATA3 FOAXA1]-患者（92%）患有晚期疾病（pT3-pT4），而 86%的 pT1-T2 病例为[GATA3 FOAXA1]+[CK5/6 CK14]-（p=0.041）。63 例 pN+原发性肿瘤及其相应 LNM 的差异抗原表达显示以下一致性百分比：p53（76%），p63（75%），CK5/6（65%），CK14（89%），GATA3（75%），FOXA1（68%），STAG2（65%）和 Ki-67（71%）。这些结果支持使用 CK5/6、CK14、GATA3 和 FOXA1 对转移性 UC 进行免疫组织化学亚组分析的兴趣，同时也强调了当肿瘤扩散到淋巴结时，表型变化很少。
