αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type

Cervical adenocarcinoma, gastric type (GAS) is not associated with human papilloma virus (HPV) infection. GAS patients prognoses are significantly worse compared with cervical adenocarcinoma associated with HPV infection, as their tumors exhibit resistance to conventional chemotherapy and radiotherapy. GAS is often associated with lobular endocervical glandular hyperplasia (LEGH), which is regarded as a precursor to GAS in the latest WHO classification. Recently, we reported that a decrease in expression of terminal alpha 1,4-linked N-acetylglucosamine (alpha GlcNAc) relative to that of MUC6 was already apparent in atypical LEGH in the LEGH-GAS sequence. Here, we analyzed expression of alpha 1,4-N-acetylglucosaminyltransferase (alpha 4GnT), the sole enzyme catalyzing alpha GlcNAc biosynthesis, and that of alpha GlcNAc and MUC6 in cases representing non-neoplastic endocervical gland (NNEG) (11 cases), LEGH (26 cases) and GAS (12 cases). alpha 4GnT protein was detected in a dot-like pattern, indicating localization in the Golgi apparatus in all 26 LEGH cases and 5 of 12 GAS cases. alpha 4GnT- and alpha GlcNAc-positive cells largely overlapped, suggesting that alpha 4GnT gene expression regulates alpha GlcNAc biosynthesis. Interestingly, all NNEG cases were negative for alpha 4GnT and alpha GlcNAc expression, but 7 of 11 NNEG and all LEGH cases were MUC6-positive. In GAS cases, patients whose tumors were alpha 4GnT- and alpha GlcNAc-positive had more favorable prognosis than others. Multivariate analysis revealed that positive expressions of alpha 4GnT and alpha GlcNAc were independent prognostic indicators. These results indicate that alpha 4GnT and alpha GlcNAc could serve as useful markers not only to distinguish LEGH from NNEG but to evaluate prognoses of GAS patients.