Ezenkwa Uchenna Simon, Ogun Gabriel Olabiyi, Mashor Mbwas Isaac, Ogunbiyi Olufemi John
Federal Medical Centre Azare, Azare 751101, Bauchi, Nigeria.
https://orcid.org/0000-0002-7022-8268.
Ecancermedicalscience. 2023 Jul 6;17:1569. doi: 10.3332/ecancer.2023.1569. eCollection 2023.
This study aimed to characterise epithelial cell adhesion molecule (EpCAM) expression patterns in colorectal carcinomas (CRC) from Nigerian patients, its association with E-cadherin and tumour characteristics, to forecast patient selection for anti-EpCAM therapy among whom no data existed previously.
Tissue microarray blocks of formalin-fixed and paraffin-embedded CRC tissues, with their non-cancer margins of resection, were sectioned and stained with EpCAM and E-cadherin primary antibodies. Scoring for antibody staining was done semiquantitatively by combining staining proportion and intensity. The outcome was correlated with patient age, gender and tumour histological parameters with ≤ 0.05 regarded as statistically significant.
Sixty-three carcinoma tissues had staining status for the two markers and were included in this study. Of these, 36 (57.1%) showed positive EpCAM expression (immunoscore ≥3) out of which 83% (30/36 positive cases) were overexpressed (combined immunoscore ≥4) while 12 (19%) tissues were positive for E-cadherin. Non-tumour margins of resection tissues showed less EpCAM positivity in 24% (6/25) of histospots. The difference in staining between tumour and non-tumour margin tissues with EpCAM was significant ( < 0.001). Also, EpCAM overexpression was significantly associated with reduced E-cadherin ( < 0.035) expression in tumour cells. Tumour extent within the gut wall was equal (50% each) for early and late pT stages among EpCAM overexpressing tumours but two-thirds (8/12) of cases expressing E-cadherin had later pT stage paradoxically, while distant metastasis was negligible among tumours bearing both markers. Also, tumours overexpressing EpCAM had significant association with tumour-associated lymphocytes ( < 0.02 each).
CRC in this study preferentially overexpress EpCAM over E-cadherin whose strong cell-cell contact inhibitory role is weakened even when expressed, resulting in further local tumour spread. This, and the observed immune response, supports targeted therapy among eligible patients.
本研究旨在描述尼日利亚患者结直肠癌（CRC）中上皮细胞粘附分子（EpCAM）的表达模式，其与E-钙粘蛋白及肿瘤特征的关联，以预测此前尚无相关数据的抗EpCAM治疗的患者选择。
将福尔马林固定、石蜡包埋的CRC组织及其癌旁切除边缘制成组织微阵列块，切片后用EpCAM和E-钙粘蛋白一抗染色。通过结合染色比例和强度对抗体染色进行半定量评分。将结果与患者年龄、性别及肿瘤组织学参数进行关联分析，P≤0.05视为具有统计学意义。
63例癌组织有这两种标志物的染色状态并纳入本研究。其中，36例（57.1%）显示EpCAM表达阳性（免疫评分≥3），其中83%（30/36例阳性病例）为过表达（联合免疫评分≥4），而12例（19%）组织E-钙粘蛋白呈阳性。切除组织的非肿瘤边缘在24%（6/25）的组织点中显示出较低的EpCAM阳性率。肿瘤组织与非肿瘤边缘组织EpCAM染色的差异具有显著性（P<0.001）。此外，EpCAM过表达与肿瘤细胞中E-钙粘蛋白表达降低显著相关（P<0.035）。在EpCAM过表达的肿瘤中，早期和晚期pT分期的肠壁内肿瘤范围相等（各占50%），但表达E-钙粘蛋白的病例中有三分之二（8/12）的pT分期较晚，而在同时具有这两种标志物的肿瘤中远处转移可忽略不计。此外，EpCAM过表达的肿瘤与肿瘤相关淋巴细胞显著相关（P均<0.02））。
本研究中的结直肠癌优先于E-钙粘蛋白过表达EpCAM，即使E-钙粘蛋白表达时其强大的细胞间接触抑制作用也会减弱，导致肿瘤进一步局部扩散。这一点以及观察到的免疫反应支持对符合条件的患者进行靶向治疗。
