Paired box proteins as diagnostic biomarkers for endocervical adenocarcinoma

Abstract

In this editorial, we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases. We focused specifically on the role of the transcription factor paired box protein 8 (PAX8) belonging to the family PAX in the carcinogenesis of a gynecologic tumor, endocervical adenocarcinoma, arising from the tissue of mesonephric origin, and the potential diagnostic value for the same type of neoplasms. The global vaccination program of human papillomavirus (HPV) has dramatically reduced the incidence of cervical cancer, including cases of adenocarcinoma. The type of adenoid epithelial origin has a lower frequency of HPV detection but tends to be more aggressive and fatal. Cases of endocervical adenocarcinoma occurring in females of menopause age have been described in the 2023 volume of the World Journal of Clinical Cases and in our study recently published in Oncol Lett. The histopathological findings and immunohistochemical assays showed that the lesions had glandular morphology, and the specimens in these two reports were immunohistochemically positive for the transcription factor PAX8, albeit that they had opposing expression profiles of tumor suppressor p16 and estrogen receptor and the presence of the HPV genome. The presence of a mucin protein, MUC 5AC, as revealed in both studies suggested target molecules for the diagnosis of mucinous adenoid type of uterine tumor and other histological origins. The clinical outcome was unfavorable due to metastasis and recurrence. This prompted the improvement of the antitumor modality, with the introduction of precise targeting therapy. Mucin has now been reported to be the therapeutic target for adenocarcinomas.

Keywords: Cervical adenocarcinoma, Diagnostic biomarker, Paired box protein 8, Embryogenesis, Transcription factor

Core Tip: Paired box proteins (PAXs) are a family of transcription factors that play an important role in the embryogenesis of different tissues through the regulation of gene expression. PAX 2, 5, and 8 are expressed in the sites of mesonephric tissues, and their deregulation contributes to the genesis of urogenital tumors such as cervical and ovarian cancers. Immunohistochemical staining and in situ hybridization tests revealed that the specimens of endocervical adenocarcinoma were positive for the transcription factor PAX8 and human papillomavirus. It is proposed that combined with mucin of glandular tumor, PAX8 can be used as a diagnostic marker for cervical adenocarcinoma.