Decreased cytokeratin 7 expression correlates with the progression of cervical squamous cell carcinoma and poor patient outcomes Mariko Hashiguchi 1,2 , Masanori Masuda 1 , Keita Kai 3 , Yoshifumi Nakao 2 , Atsushi Kawaguchi 4 , Masatoshi Yokoyama 2 and Shinichi Aishima 1,3 Departments of 1 Pathology & Microbiology, Faculty of Medicine, 2 Obstetrics & Gynecology, Faculty of Medicine, Saga University, 3 Department of Pathology, Saga University Hospital and 4 Center for Comprehensive Community Medicine, Saga University Faculty of Medicine, Saga, Japan Abstract Aim: To identify potential biomarkers for tumor progression and patient outcomes in cervical squamous cell carcinoma. Methods: We examined the expressions of CK7 and CK17 as potential markers of the squamo-columnar junction, and podoplanin as a basal cell marker using surgical and biopsy samples of patients in grade 3 cer- vical intraepithelial neoplasia (n = 30), operable invasive carcinoma (OP group, n = 53) and inoperable inva- sive carcinoma before radiotherapy and/or chemotherapy (RC group, n = 76). Results: The positive rates of CK7 and podoplanin in invasive carcinoma were significantly lower than those in grade 3 cervical intraepithelial neoplasia (P = 0.001, P < 0.0001). The positive rates of CK7 and podoplanin in the RC group were significantly lower than those in the OP group (P < 0.0001, P = 0.04), while CK17 expression showed significantly higher positivity in the RC group than in the OP group (P < 0.0001). Negative CK7 expression showed a potential impact on overall survival in early-stage patients. In the RC group, the prevalence of cases with post-therapeutic residual carcinoma cells was higher in the CK7-negative group than in the positive group (P = 0.003). We found that decreased expression of CK7 could be a prognostic factor in early-stage cervical cancer patients. Conclusion: This result may provide strategies and suggestions for new treatment options and follow-up practices in managing patients with cervical cancer. Key words: cervical cancer, CK17, CK7, podoplanin, squamous cell carcinoma. Introduction Cervical cancer is the fourth most-common cause of cancer death among women worldwide. 1 Almost all cervical cancers are caused by persistent infections with carcinogenic types of human papilloma virus (HPV). It develops in a multistep process from cervi- cal squamous intraepithelial neoplastic lesions to invasive cancer. In Japan, the standard treatment for cervical cancer – i.e., surgery, chemotherapy, or radiation therapy – is selected according to the stag- ing system of the International Federation of Gynecol- ogy and Obstetrics (FIGO). Because younger patients who wish to preserve their fertility are increasing in number, the detection of biomarkers and the predic- tion of patient outcomes is becoming especially important for the treatment of cervical cancer. Cervical cancer arises in the squamo-columnar junc- tion (SCJ). Cytokeratin 7 (CK7) is one of the markers of SCJ cells, 2 and CK7 positivity in low-grade cervical Received: March 6 2019. Accepted: August 14 2019. Correspondence: Professor Shinichi Aishima, Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga City, Saga, 849-8501, Japan. Email: saish@cc.saga-u.ac.jp 1 © 2019 Japan Society of Obstetrics and Gynecology doi:10.1111/jog.14108 J. Obstet. Gynaecol. Res. 2019