Galema Hidde A, Neijenhuis Lisanne K A, Lauwerends Lorraine J, Dekker-Ensink N Geeske, Verhoef Cornelis, Vahrmeijer Alexander L, Bhairosingh Shadhvi S, Kuppen Peter J K, Rogalla Stephan, Burggraaf Jacobus, Lagarde Sjoerd M, Wijnhoven Bas P L, Hutteman Merlijn, Doukas Michail, Keereweer Stijn, Hilling Denise E
Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Mol Imaging Biol. 2024 Dec;26(6):955-964. doi: 10.1007/s11307-024-01962-6. Epub 2024 Nov 19.
Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR indicate that identification of a true complete response to nCRT remains challenging. Near-infrared tumour-specific fluorescence endoscopic imaging might help to discriminate patients with a true complete response from patients with residual disease. This study aims to find potential markers to enable molecular imaging in oesophageal cancer and to assess the effect of nCRT on marker expression.
Oesophageal cancer tissue slides of diagnostic biopsies (n = 41) (pre-treatment) and paired surgical specimens (n = 31) (post-treatment) were collected. Tissue slides of patients with adenocarcinoma (n = 29) and squamous cell carcinoma (n = 12)) were included. Immunohistochemistry was performed to assess expression of the tumour markers CEA, EpCAM, VEGF-α, EGFR, and c-MET in the tumour and compared to the expression of these markers in surrounding healthy tissue. A total immunostaining score (TIS, range 0-12), which combines the percentage and intensity of stained cells, was calculated. The TIS of pre-treated biopsies were compared with the TIS of the post-treatment surgical specimens to assess the effect of neoadjuvant therapy on the marker expression.
The median TIS of EpCAM in adenocarcinomas was 10, vs. 0 in healthy mucosa (p < 0.001). The median TIS of EGFR in squamous cell carcinoma was 12, vs. 4 in healthy mucosa (p < 0.001). Neoadjuvant therapy did not affect the expression of the markers.
EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.
新辅助放化疗(nCRT)后达到临床完全缓解(CR)的食管癌患者是积极监测策略的候选对象。初始临床CR后40%的复发率表明,识别对nCRT的真正完全缓解仍然具有挑战性。近红外肿瘤特异性荧光内镜成像可能有助于区分真正完全缓解的患者和有残留疾病的患者。本研究旨在寻找潜在标志物以实现食管癌的分子成像,并评估nCRT对标志物表达的影响。
收集诊断性活检(n = 41)(治疗前)和配对手术标本(n = 31)(治疗后)的食管癌组织切片。纳入腺癌患者(n = 29)和鳞状细胞癌患者(n = 12)的组织切片。进行免疫组织化学以评估肿瘤标志物癌胚抗原(CEA)、上皮细胞黏附分子(EpCAM)、血管内皮生长因子-α(VEGF-α)、表皮生长因子受体(EGFR)和c-甲硫氨酸(c-MET)在肿瘤中的表达,并与这些标志物在周围健康组织中的表达进行比较。计算总免疫染色评分(TIS,范围0 - 12),该评分结合了染色细胞的百分比和强度。比较治疗前活检的TIS与治疗后手术标本的TIS,以评估新辅助治疗对标志物表达的影响。
腺癌中EpCAM 的中位TIS为10,而健康黏膜中为0(p < 0.001)。鳞状细胞癌中EGFR的中位TIS为12,而健康黏膜中为4(p < 0.001)。新辅助治疗不影响标志物的表达。
EpCAM和EGFR似乎分别是食管腺癌和鳞状细胞癌肿瘤特异性近红外荧光成像的最合适靶点。新辅助治疗对所有合适标志物的表达无影响,这意味着诊断性活检可用于选择患者特异性靶点,通过分子成像进行反应评估。