?GlcNAc and its catalyst ?4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type.

ABSTRACT: 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 ?1,4-linked N-acetylglucosamine (?GlcNAc) relative to that of MUC6 was already apparent in atypical LEGH in the LEGH-GAS sequence. Here, we analyzed expression of ?1,4-N-acetylglucosaminyltransferase (?4GnT), the sole enzyme catalyzing ?GlcNAc biosynthesis, and that of ?GlcNAc and MUC6 in cases representing non-neoplastic endocervical gland (NNEG) (11 cases), LEGH (26 cases) and GAS (12 cases). ?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. ?4GnT- and ?GlcNAc-positive cells largely overlapped, suggesting that ?4GnT gene expression regulates ?GlcNAc biosynthesis. Interestingly, all NNEG cases were negative for ?4GnT and ?GlcNAc expression, but 7 of 11 NNEG and all LEGH cases were MUC6-positive. In GAS cases, patients whose tumors were ?4GnT- and ?GlcNAc-positive had more favorable prognosis than others. Multivariate analysis revealed that positive expressions of ?4GnT and ?GlcNAc were independent prognostic indicators. These results indicate that ?4GnT and ?GlcNAc could serve as useful markers not only to distinguish LEGH from NNEG but to evaluate prognoses of GAS patients.

SUBMITTER: Ida K 

PROVIDER: S-EPMC6737144 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature