The sensitivity and specificity of Claudin18.2 and MUC6 in the differential diagnosis of endocervical gastric-type glandular lesions

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.