RAD51 Expression as a Biomarker to Predict Efficacy of Preoperative Therapy and Survival for Esophageal Squamous Cell Carcinoma: A Large-cohort Observational Study (KSCC1307). Issue 4 (29th April 2022)

• Record Type: Journal Article
• Authors: Saeki, Hiroshi; Jogo, Tomoko; Kawazoe, Tetsuro; Kamori, Tomohiro; Nakaji, Yu; Zaitsu, Yoko; Fujiwara, Minako; Baba, Yoshifumi; Nakamura, Tetsu; Iwata, Naoki; Egashira, Akinori; Nakanoko, Tomonori; Morita, Masaru; Tanaka, Yoshihiro; Kimura, Yasue; Shibata, Tomotaka; Nakashima, Yuichiro; Emi, Yasunori; Makiyama, Akitaka; Oki, Eiji; Tokunaga, Shoji; Shimokawa, Mototsugu; Mori, Masaki
• Is Part Of: Annals of surgery. Volume 275:Issue 4(2022)
• Page Start: 692
• Page End: 699
• Publication Date: 2022-04-29
• Subjects: biomarker -- chemoradiotherapy -- pathological effect -- prognosis -- RAD51; Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000003975
• Languages: English
• ISSNs: 0003-4932

Abstract

Abstract : Objective: The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). Background: It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study. Methods: A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry. Results: In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 ( P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors ( P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT. Conclusions: In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.