Zhong Fangfang, Ren Zuocheng, Li Wei, Jones Terrell, Zeng Xianxu, Wang Shuni, Tao Xiang, Zhao Chengquan
Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Hum Pathol. 2025 Jun;160:105837. doi: 10.1016/j.humpath.2025.105837. Epub 2025 Jun 7.
Endocervical gastric-type adenocarcinoma (GAS) when well-differentiated or with less mucin may lead to misdiagnosis, particularly in biopsy specimens. This study aimed to evaluate the sensitivity and specificity of Claudin18.2 and MUC6 in the diagnosis of GAS and its precursor lesions. 167 cases from the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University (OGHFU) were selected, including 43 cases of usual type endocervical adenocarcinoma (UEA), 43 cases of GAS, 20 lobular endocervical glandular hyperplasia (LEGH) cases, 21 atypical LEGH (ALEGH) cases, and 40 normal/benign cases. A panel of immunohistochemical stains (IHC) for Claudin18.2, MUC6, P53, and P16 were performed on all cases. IHC expression in >5 % tumor cells was considered positive for Claudin18.2 and MUC6. An IHC composite score was calculated by multiplying the individual scores of extents by intensity. P53 was considered positive/mutant with the presence of strong nuclear reactivity in ≥75 % of cells (overexpression), was completely negative (null expression), or showed cytoplasmic staining. P16 was considered positive if diffuse block-type staining. Claudin18.2 was positive in all cases of LEGH and ALEGH and 83.7 % (36/43) GAS cases but was negative in all UEA and benign cases. MUC6 was positive in all LEGH and ALEGH cases, 88.4 % (38/43) of GAS cases, as well as 40.0 % (16/40) of benign and 20.9 % (9/43) of UEA cases. P53 mutant expression was found in 62.8 % (27/43) of GAS cases, 10 of which showed P16 diffuse staining and 10 of which were completely negative for P16. The composite scores of both Claudin18.2 and MUC6 were higher in ALEGH/LEGH than in GAS. Claudin 18.2 is a sensitive and specific marker for cervical gastric-type glandular lesions, not expressed in normal cervical tissues but expressed in all of the LEGH/ALEGH cases. However, it was not helpful in differentiating GAS from ALEGH. MUC6 is a highly sensitive marker for LEGH and GAS, yet its specificity is much lower than that of Claudin18.2. Taking morphology as the cornerstone and combining immunomarkers such as P16, P53, Claudin18.2 and MUC6 can significantly enhance the diagnostic efficiency of gastric-type glandular lesions.
宫颈胃型腺癌（GAS）在高分化或黏液较少时可能导致误诊，尤其是在活检标本中。本研究旨在评估Claudin18.2和MUC6在诊断GAS及其前驱病变中的敏感性和特异性。选取了复旦大学附属妇产科医院病理科的167例病例，包括43例宫颈原位腺癌（UEA）、43例GAS、20例宫颈小叶腺性增生（LEGH）、21例非典型LEGH（ALEGH）以及40例正常/良性病例。对所有病例进行了Claudin18.2、MUC6、P53和P16的免疫组织化学染色（IHC）检测。Claudin18.2和MUC6在>5%肿瘤细胞中的IHC表达被视为阳性。通过将范围得分与强度得分相乘计算IHC综合评分。P53在≥75%细胞中存在强核反应性（过表达）、完全阴性（无表达）或显示胞质染色时被视为阳性/突变型。P16如果呈弥漫性块状染色则被视为阳性。Claudin18.2在所有LEGH和ALEGH病例以及83.7%（36/43）的GAS病例中呈阳性，但在所有UEA和良性病例中呈阴性。MUC6在所有LEGH和ALEGH病例、88.4%（38/43）的GAS病例以及40.0%（16/40）的良性病例和20.9%（9/43）的UEA病例中呈阳性。在62.8%（27/43）的GAS病例中发现P53突变表达，其中10例显示P16弥漫性染色，10例P16完全阴性。ALEGH/LEGH中Claudin18.2和MUC6的综合评分均高于GAS。Claudin 18.2是宫颈胃型腺性病变的敏感和特异性标志物，在正常宫颈组织中不表达，但在所有LEGH/ALEGH病例中表达。然而，它对区分GAS和ALEGH并无帮助。MUC6是LEGH和GAS的高敏感标志物，但其特异性远低于Claudin18.2。以形态学为基石，结合P16、P53、Claudin18.2和MUC6等免疫标志物可显著提高胃型腺性病变的诊断效率。
