Yan Pingping, Dong Yu, Zhang Fenfen, Zhen Tiantian, Liang Jiangtao, Shi Huijuan, Han Anjia
Department of Pathology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.
Department of Pathology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China
J Clin Pathol. 2024 Mar 28. doi: 10.1136/jcp-2023-209268.
To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma.
Immunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and gene rearrangement in adenocarcinoma from different organs.
The results showed that claudin18.2 expression was found in 68% (27 of 40) of lung mucinous adenocarcinoma, 52% (16 of 31) of cholangiocarcinoma, 2% (10 of 423) of colorectal adenocarcinoma tissue microarray, 27% (6 of 22) of colorectal mucinous adenocarcinoma and 30% (3 of 10) of cervical adenocarcinoma, but not in all 39 cases of invasive breast adenocarcinoma by immunohistochemistry staining. There was significantly positive correlation between ratio of claudin18.2-positive carcinoma cells and staining intensity in lung mucinous adenocarcinoma and cholangiocarcinoma. Claudin18.2 expression was much more in female patients than male patients with lung mucinous adenocarcinoma. In addition, cholangiocarcinoma with claudin18.2 expression was more aggressive and had perineural invasion. Intraductal papillary neoplasm of the bile duct and epithelial dysplasia of the adjacent bile in cholangiocarcinoma also showed claudin18.2 expression. All three cases of cervical adenocarcinoma with claudin18.2 expression were moderately differentiated adenocarcinoma including one human papillomavirus (HPV)-associated carcinoma, two non-HPV-associated and gastric-type carcinoma. gene rearrangement was not found in all 22 cases with high claudin18.2 expression by FISH.
Our results suggest claudin18.2 might be a potential biomarker for targeted therapy on lung mucinous adenocarcinoma, cholangiocarcinoma, colorectal mucinous adenocarcinoma and gastric-type cervical adenocarcinoma.
明确紧密连接蛋白18.2（claudin18.2）在各种癌症，尤其是肺腺癌中的表达及其临床病理特征。
采用免疫组织化学染色和荧光原位杂交（FISH）检测不同器官腺癌中claudin18.2的表达及基因重排。
结果显示，通过免疫组织化学染色，在68%（40例中的27例）的肺黏液腺癌、52%（31例中的16例）的胆管癌、2%（423例结直肠腺癌组织芯片中的10例）、27%（22例中的6例）的结直肠黏液腺癌和30%（10例中的3例）的宫颈腺癌中发现claudin18.2表达，但在所有39例浸润性乳腺腺癌中均未发现。在肺黏液腺癌和胆管癌中，claudin18.2阳性癌细胞比例与染色强度之间存在显著正相关。肺黏液腺癌女性患者中claudin18.2表达明显高于男性患者。此外，表达claudin18.2的胆管癌侵袭性更强且有神经周围侵犯。胆管内乳头状肿瘤及胆管癌相邻胆管的上皮发育异常也显示claudin18.2表达。所有3例表达claudin18.2的宫颈腺癌均为中分化腺癌，其中1例与人乳头瘤病毒（HPV）相关癌、2例非HPV相关的胃型癌。通过FISH在所有22例claudin18.2高表达病例中均未发现基因重排。
我们的结果表明，claudin18.2可能是肺黏液腺癌、胆管癌、结直肠黏液腺癌和胃型宫颈腺癌靶向治疗的潜在生物标志物。
