Validation of Potential Protein Markers Predicting Chemoradioresistance in Early Cervical Cancer by Immunohistochemistry

Soo Young Jeong; Joon-Yong Chung; Sun-Ju Byeon; Chul Jung Kim; Yoo-Young Lee; Tae-Joong Kim; Jeong-Won Lee; Byoung-Gie Kim; Ye Lin Chae; So Young Oh; Chel Hun Choi

doi:10.3389/fonc.2021.665595

Validation of Potential Protein Markers Predicting Chemoradioresistance in Early Cervical Cancer by Immunohistochemistry

Front Oncol. 2021 Jul 19:11:665595. doi: 10.3389/fonc.2021.665595. eCollection 2021.

Authors

Affiliations

¹ Departments of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
² Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
³ Departments of Pathology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea.
⁴ Departments of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon, South Korea.

Abstract

Background: In a previous study, a proteomic panel consisting of BCL-2, HER2, CD133, CAIX, and ERCC1 significantly predicted survival in patients with locally advanced cervical cancer. However, the prognostic significance of these proteins has not been assessed in early cervical cancer. The present study investigated the clinical significance and chemoradioresistance prediction power of these proteins in patients with early-stage cervical cancer.

Materials and methods: BCL-2, HER2, CD133, CAIX, and ERCC1 expression was determined by the immunohistochemical staining of 336 cervical cancer tissue microarrays. The associations of these proteins with clinicopathologic characteristics and disease progression were assessed.

Results: There was a trend of low CAIX expression (p=0.082) and high ERCC1 expression (p=0.059) in patients with a favorable response to adjuvant radiation. High HER2 expression was significantly associated with shorter disease-free survival (DFS) in the total group (5-year DFS of 80.1% vs. 92.2%, p=0.004). A prognostic significance remained in multivariate analysis (Hazard ratio, HR=2.10, p=0.029). In the adjuvant radiation group, low CAIX and high ERCC1 expression indicated significantly unfavorable DFS (75.0% vs. 89.0%, p=0.026 and 76.8% vs. 88.6%, p=0.022, respectively). Low CAIX expression remained an independent prognostic marker in multivariate analysis (HR=0.45, p=0.037). The combined molecular-clinical model using random survival forest method predicted DFS with improved power compared with that of the clinical variable model (C-index 0.77 vs. 0.71, p=0.006).

Conclusion: HER2, CAIX, and ERCC1 expression can be predictive protein markers for clinical outcomes in early cervical cancer patients treated primarily with radical surgery with or without adjuvant radiation.

Keywords: CAIX; ERCC1; HER2; chemoradioresistance; immunohistochemistry; uterine cervical neoplasm.