Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence tumor imaging by endoscopy to differentiate responders and the effect of nCRT on their expression. Methods: RC samples (n= 51) were collected from both pre-treatment biopsies and corresponding post-treatment surgical specimens. Samples were categorized by treatment response and determined using tumor regression grade (TRG) scoring. Immunohistochemistry assessed the expression of CEA, EpCAM, EGFR, and c-MET in tumors and adjacent normal tissues. Expression levels were quantified using H-scores (0–3), combining the percentage and intensity of stained cells. Pre- and post-treatment H-scores were compared to evaluate the impact of nCRT. Results: CEA, EpCAM, and c-MET were overexpressed in tumor tissue as compared to adjacent healthy mucosa in 100% (51/51), 98.4% (50/51), and 92% (47/51) of tumor biopsies, respectively, while EGFR showed no overexpression. A tumor-to-normal (T/N) ratio ≥ 2 was considered sufficient for differentiation in molecular fluorescence imaging. In pre-treatment biopsy samples, c-MET showed the highest T/N expression ratio (53% of the samples ≥ 2), followed by CEA (26.3%) and EpCAM (16%). Following nCRT treatment, CEA and c-MET maintained a ≥ 2 differential expression in 45% of all samples, whereas EpCAM exhibited this difference in only 9.2% of cases. Neoadjuvant therapy even significantly improved the T/N expression ratio for CEA and c-MET (p< 0.01) and EpCAM (p< 0.05), while EGFR expression remained lower than adjacent normal tissue. Significant increases in all marker expressions were observed in minimal responders (TRG4/5,p< 0.01–0.001), while near-complete responders (TRG2) exhibited non-significant changes in CEA, c-MET, and EGFR expression. Conclusions: c-MET and CEA emerged as optimal tumor imaging targets, showing sustained differential expression after nCRT. In vivo fluorescence-guided endoscopy using probes against these markers could play a role in future clinical decision-making.
背景：直肠癌患者在新辅助放化疗后达到临床完全缓解，可能适合采用观察等待策略。然而，20-30%的局部肿瘤再生率凸显了识别真正应答者所面临的挑战。本研究旨在探索未来内镜下近红外荧光肿瘤成像的标记物，以区分应答者，并评估新辅助放化疗对这些标记物表达的影响。方法：收集51例直肠癌患者的治疗前活检样本及对应的治疗后手术标本。根据肿瘤退缩分级评估治疗反应并对样本进行分类。采用免疫组织化学法检测肿瘤组织及邻近正常组织中CEA、EpCAM、EGFR和c-MET的表达水平。通过H评分（0-3分）结合染色细胞百分比和强度对表达水平进行量化。比较治疗前后H评分以评估新辅助放化疗的影响。结果：在肿瘤活检组织中，CEA、EpCAM和c-MET相较于邻近健康黏膜的过表达率分别为100%（51/51）、98.4%（50/51）和92%（47/51），而EGFR未显示过表达。肿瘤与正常组织的表达比值≥2被认为足以在分子荧光成像中进行区分。在治疗前活检样本中，c-MET的T/N表达比值最高（53%的样本≥2），其次是CEA（26.3%）和EpCAM（16%）。新辅助放化疗后，CEA和c-MET在45%的样本中维持≥2的差异表达，而EpCAM仅9.2%的病例显示此差异。新辅助治疗显著提高了CEA和c-MET（p<0.01）以及EpCAM（p<0.05）的T/N表达比值，而EGFR表达仍低于邻近正常组织。在轻微应答者中观察到所有标记物表达均显著增加（TRG4/5，p<0.01-0.001），而接近完全应答者中CEA、c-MET和EGFR表达变化不显著。结论：c-MET和CEA成为最佳的肿瘤成像靶点，在新辅助放化疗后仍保持差异表达。针对这些标记物的体内荧光引导内镜检查可能在未来临床决策中发挥作用。
肿瘤(癌症)患者之家