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

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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.

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Acknowledgements

The authors thank Dr. Elise Lamar for editing the manuscript.

Founding

This work was supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (nos. 17K15640 (K.Y.) and 15H04712 (J.N.)).

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Authors and Affiliations

  1. Department of Molecular Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Kazuhiro Yamanoi, Michihiko Tsukamoto & Jun Nakayama

  2. Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, 390-8621, Japan

    Kazuhiro Yamanoi & Jun Nakayama

  3. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, 390-8621, Japan

    Keiko Ishii & Shiho Asaka

  4. Department of Pathology, Okaya City Hospital, Okaya, 394-8512, Japan

    Keiko Ishii

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  1. Kazuhiro Yamanoi
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Correspondence to Kazuhiro Yamanoi.

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This study was approved by the ethics committee of Shinshu University School of Medicine, Japan (project no. 3737 was approved on July 4, 2017).

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Yamanoi, K., Ishii, K., Tsukamoto, M. et al. Gastric gland mucin-specific O-glycan expression decreases as tumor cells progress from lobular endocervical gland hyperplasia to cervical mucinous carcinoma, gastric type. Virchows Arch 473, 305–311 (2018). https://doi.org/10.1007/s00428-018-2381-6

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  • DOI: https://doi.org/10.1007/s00428-018-2381-6

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