UNASSIGNED: In this pilot study, we analyzed formalin-fixed paraffin-embedded (FFPE) tumor resection specimen from patients with histologically confirmed squamous cell carcinoma (SCC; n = 10) or adenocarcinoma (A; n = 10) of the esophagus, having undergone neoadjuvant radiochemotherapy followed by resection (NRCHT + R) or resection (R)]. FFPE tissue sections were analyzed by immunohistochemistry regarding tumor hypoxia (HIF-1α), proliferation (Ki67), immune status (PD1), cancer cell stemness (CXCR4), and p53 mutation status. Marker expression in HIF-1α subvolumes was part of a sub-analysis. Statistical analyses were performed using one-sided Mann-Whitney tests and Bland-Altman analysis.
UNASSIGNED: In both SCC and AC patients, the overall percentages of positive tumor cells among the five TME markers, namely HIF-1α, Ki67, p53, CXCR4 and PD1 after NRCHT were lower than in the R cohort. However, only PD1 in SCC and Ki67 in AC showed significant association (Ki67: p = 0.03, PD1: p = 0.02). In the sub-analysis of hypoxic subvolumes among the AC patients, the percentage of positive tumor cells within hypoxic regions were statistically significantly lower in the NRCHT than in the R cohort across all the markers except for PD1.
UNASSIGNED: In this pilot study, we showed changes in the TME induced by NRCHT in both SCC and AC. These findings will be correlated with microscopic tumor extension measurements in a subsequent cohort of patients.
■在这项试点研究中,我们分析了经组织学证实的食管鳞状细胞癌(SCC;n=10)或腺癌(A;n=10)患者的福尔马林固定石蜡包埋(FFPE)肿瘤切除标本,已接受新辅助放化疗,然后进行切除术(NRCHTR)或切除术(R)]。FFPE组织切片通过免疫组织化学分析肿瘤缺氧(HIF-1α),增殖(Ki67),免疫状态(PD1),癌细胞干性(CXCR4),和p53突变状态。HIF-1α亚体积中的标志物表达是亚分析的一部分。使用单侧Mann-Whitney检验和Bland-Altman分析进行统计分析。
■在SCC和AC患者中,五种TME标志物中阳性肿瘤细胞的总百分比,即HIF-1α,NRCHT后Ki67、p53、CXCR4和PD1低于R组。然而,只有SCC中的PD1和AC中的Ki67表现出显著的相关性(Ki67:p=0.03,PD1:p=0.02).在对AC患者缺氧亚体积的亚分析中,在除PD1以外的所有标志物中,NRCHT中缺氧区域内的阳性肿瘤细胞百分比在统计学上显著低于R队列.
■在这项试点研究中,我们显示了在SCC和AC中NRCHT诱导的TME的变化。这些发现将与随后的患者队列中的微观肿瘤延伸测量相关联。