Gastric gland mucin-specific O-glycan expression decreases as tumor cells progress from lobular endocervical gland hyperplasia to cervical mucinous carcinoma, gastric type

Abstract

Gastric gland mucin-specific O-glycans are unique in having α1,4-linked N-acetylglucosamine (αGlcNAc) attached to MUC6. We previously reported decreased expression of αGlcNAc relative to MUC6 in gastric and pancreatic neoplasms, but its significance in cervical glandular lesions remained unclear. Here, we analyzed MUC5AC, MUC6, αGlcNAc, and p16 expression in 9 lesions of mucinous carcinoma, gastric type with minimal deviation adenocarcinoma (GAS-MDA), 5 of GAS with nonMDA (GAS-nonMDA), 14 of typical lobular endocervical gland hyperplasia (LEGH), and 5 of atypical LEGH (33 total lesions). All 33 were MUC5AC-positive. Moreover, all 14 typical LEGH, 5 atypical LEGH, 8 of 9 GAS-MDA, and 3 of 5 GAS-nonMDA were MUC6-positive. All 14 typical LEGH, 2 of 5 atypical LEGH, 3 of 9 GAS-MDA, and 1 of 5 GAS-nonMDA were αGlcNAc-positive. The proportion of αGlcNAc-positive atypical LEGH or GAS-MDA or GAS-nonMDA lesions was significantly smaller than that seen in typical LEGH lesions (P < 0.001 and P < 0.01, respectively). Of 33 lesions, 32 were p16-negative. Furthermore, when we evaluated MUC6 and αGlcNAc immunoreactivity semi-quantitatively in all 33 lesions, in typical LEGH and GAS-MDA, the immunohistochemical score for αGlcNAc was significantly lower than that for MUC6 (P < 0.01). We did not observe significantly decreased αGlcNAc expression relative to MUC6 in typical LEGH lesions. These studies suggest that αGlcNAc expression decreases as typical LEGH progresses to GAS. Given the difficulty in distinguishing MDA and atypical LEGH from typical LEGH in H.E. staining, we propose that immunohistochemical analysis of αGlcNAc and MUC6 could be useful.

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

“…We previously reported decreased αGlcNAc expression not only in cancer but in pre-malignant lesions of the human stomach, pancreas and uterine cervix 23,25,29 . In the latter, αGlcNAc expression decreases from typical LEGH to atypical LEGH or MDA 30 . These results indicate that decreased αGlcNAc expression is related to tumor progression from pre-malignant to a malignant status.…”

“…In pancreas, we observed significantly decreased αGlcNAc expression relative to MUC6 not only in invasive carcinoma but in its pre-malignant lesions, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia 25,29 . Furthermore, we recently reported that αGlcNAc and MUC6 are co-expressed in typical LEGH, but αGlcNAc expression is reduced relative to MUC6 in atypical LEGH and minimal deviation adenocarcinoma (MDA) 30 . These findings support the idea that reduced αGlcNAc expression relative to MUC6 marks progression from pre-malignant lesions to cancers showing pyloric gland phenotypes in stomach, pancreas and uterine cervix and that αGlcNAc functions as a tumor suppressor.…”

A combination of cytokeratin 5/6, p63, p40 and MUC5AC are useful for distinguishing squamous cell carcinoma from adenocarcinoma of the cervix

“…It is also expressed in the endocervix. Yamanoi et al found that MUC5AC was largely expressed in typical LEGH, atypical LEGH, GAS-MDA, and GAS-nonMDA [26]. Thus, we speculated that MUC5AC could be expressed in other adenocarcinomas and might be used for the differential diagnosis of adenocarcinoma and squamous carcinoma.…”

A combination of cytokeratin 5/6, P63, P40 and MUC5AC are useful for distinguishing squamous cell carcinoma from adenocarcinoma of the cervix

“…It is also expressed in the endocervix. Yamanoi et al found that MUC5AC was largely expressed in typical LEGH, atypical LEGH, GAS-MDA, and GAS-nonMDA [24]. Thus, we speculated that MUC5AC could be expressed in other adenocarcinomas and might be used for the differential diagnosis of adenocarcinoma and squamous carcinoma.…”