Elevated expression of G protein-coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma

Yoshihiko Ino^1,2*, Taishi Akimoto¹*, Akira Takasawa², Kumi Takasawa², Tomoyuki Aoyama^2,3, Asako Ueda², Misaki Ota², Kazufumi Magara², Yohei Tagami², Masaki Murata², Tadashi Hasegawa³, Tsuyoshi Saito¹, Norimasa Sawada² and Makoto Osanai<sup>2

1</sup>Department of Obstetrics and Gynecology, ²Department of Pathology and ³Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
*These authors contributed equally to this work

Offprint requests to: Akira Takasawa, Department of Pathology, Sapporo Medical University School of Medicine, S1 W17, Chuo-ku, Sapporo, 0608556, Japan. e-mail: atakasawa@sapmed.ac.jp

Summary. Uterine cervical adenocarcinoma has a worse prognosis than that of squamous cell carcinoma and useful diagnostic and prognostic markers are needed. Estrogen is one of the key regulators of several cancers, however, the estrogen signaling has not been focused on in cervical adenocarcinoma. Here, we shows expression profile of classical estrogen receptor (ER) and a novel membrane type estrogen receptor, G protein-coupled receptor 30 (GPR30), in surgical specimens (n=53). GPR30 was strongly expressed on the cell membrane and in the cytoplasm in adenocarcinoma in situ (AIS) and adenocarcinoma, and its expression was especially strong at the invasion front in most of the cases of GPR30-positive adenocarcinoma. Nuclear staining of ER was strong in non-neoplastic glands, whereas it was almost absent in most of the AIS and adenocarcinoma cases. There was a weak but statistically significant negative correlation between immunoreactivity of GPR30 and that of ER in cervical AIS and adenocarcinoma lesions (Spearman's correlation, r=-0.324, p=0.017). ROC curve analysis revealed that immunoreactivity of GPR30 successfully distinguished neoplasms from non-neoplastic glands with high specificity (100%) and sensitivity (75.5%). GPR30 positivity was significantly correlated with histological type (p=0.009), tumor diameter (p=0.003), tumor size (p<0.001), lymphovascular infiltration (p=0.005) and UICC stage (p<0.001). ER expression was correlated only with tumor factor (p=0.047). GPR30-high patients had poor prognosis with a significantly shorter overall survival (OS) period (p=0.0309). GPR30 expression is a potential diagnostic and prognostic marker. Histol Histopathol 35, 351-359 (2020)

Key words: Cervical adenocarcinoma, Estrogen receptor, G protein-coupled receptor 30 (GPR30), G protein-coupled estrogen receptor 1 (GPER1), Invasion front, prognosis

DOI: 10.14670/HH-18-157