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Trefoil factor family 2 protein: a potential immunohistochemical marker for aiding diagnosis of lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma of the uterine cervix

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Abstract

Gastric-type adenocarcinoma (GA) is an aggressive subtype of cancer of the uterine cervix. Several immunohistochemical markers for gastric mucins, such as mucin 6 (MUC6) and N-acetylglucosamine α1 → 4galactose → R (αGlcNAc-R), which is recognized by HIK1083 antibody, have been introduced for diagnosis of GA and lobular endocervical glandular hyperplasia (LEGH). However, MUC6 is also expressed in normal endocervical glands and HIK1083 antibody has limited availability. Trefoil factor family 2 protein (TFF2) is secreted by gastric, but not normal endocervical glands. Here, we evaluated TFF2 immunostaining for detection of a gastric immunophenotype in endocervical glandular lesions. We compared TFF2, αGlcNAc-R, and MUC6 expression in 103 endocervical glandular lesions: LEGH (n = 23), adenocarcinoma in situ/microinvasive adenocarcinoma (AIS–MIA) (n = 29), and invasive adenocarcinoma (usual type [UA], n = 26; GA, n = 11; intestinal type [IA], n = 2; signet ring cell type [Sig], n = 2; and mucinous adenocarcinoma not otherwise specified [NOS], n = 10). TFF2 and αGlcNAc-R expression was completely concordant in each subtype: LEGH (100%), AIS–MIA (44.8%), UA (26.9%), GA (90.9%), IA (100%), Sig (0%), and NOS (20%). TFF2 staining scores were significantly correlated with those of αGlcNAc-R in these lesions. TFF2 and αGlcNAc-R immunoreactivity was present in cytoplasmic mucins and luminal secretions. TFF2 and αGlcNAc-R were not expressed in the normal endocervical glands. MUC6 was frequently expressed in normal endocervical glands and endocervical glandular lesions. Endocervical adenocarcinomas sometimes stained only for MUC6. TFF2 is a promising immunohistochemical marker and its identification in uterine cervical secretion is a potentially useful diagnostic test for endocervical glandular lesions with gastric differentiation.

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Acknowledgements

We thank Kayo Suzuki and Misako Yamada, research center for supports to advanced science, Shinshu University for providing expert technical assistance, and Dr. Trish Reynolds, MBBS, FRACP, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This work was funded by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) for H.O. (26460673).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

    Shiho Asaka, Tomoyuki Nakajima, Masanobu Momose & Takeshi Uehara

  2. Department of Diagnostic Pathology, Shinshu University Hospital, Matsumoto, Japan

    Shiho Asaka & Takeshi Uehara

  3. Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan

    Tsutomu Miyamoto

  4. Department of Clinical Laboratory Sciences, School of Health Sciences, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Hiroyoshi Ota

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  1. Shiho Asaka
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  2. Tomoyuki Nakajima
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  3. Masanobu Momose
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Contributions

Shiho Asaka: acquisition of data; analysis and interpretation of data; drafting of the manuscript; immunohistochemistry staining. Tomoyuki Nakajima: acquisition of data; analysis and interpretation of data; immunohistochemistry staining. Masanobu Momose: acquisition of data; analysis and interpretation of data; immunohistochemistry staining. Tsutomu Miyamoto: material support; analysis and interpretation of data; critical revision of the manuscript for important intellectual content. Takeshi Uehara: material support; analysis and interpretation of data; critical revision of the manuscript for important intellectual content. Hiroyoshi Ota: acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; obtaining funding; administrative, technical, or study supervision. All authors contributed to discussions and gave their final approval for the submitted manuscript.

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Correspondence to Hiroyoshi Ota.

Ethics declarations

This study was reviewed and approved by the medical ethics committee of the Shinshu University School of Medicine, Japan (project no. 1875, approved on 6 December, 2011).

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The authors declare that they have no conflict of interest.

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Asaka, S., Nakajima, T., Momose, M. et al. Trefoil factor family 2 protein: a potential immunohistochemical marker for aiding diagnosis of lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma of the uterine cervix. Virchows Arch 474, 79–86 (2019). https://doi.org/10.1007/s00428-018-2469-z

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