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

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.

• Authors: Hiroshi Saeki, Tomoko Jogo, Tetsuro Kawazoe, Tomohiro Kamori, Yu Nakaji, Yoko Zaitsu, Minako Fujiwara, Yoshifumi Baba, Tetsu Nakamura, Naoki Iwata, Akinori Egashira, Tomonori Nakanoko, Masaru Morita, Yoshihiro Tanaka, Yasue Kimura, Tomotaka Shibata, Yuichiro Nakashima, Yasunori Emi, Akitaka Makiyama, Eiji Oki, Shoji Tokunaga, Mototsugu Shimokawa, Masaki Mori, Kyushu Study Group of Clinical Cancer (KSCC)
• Journal: Annals of surgery (Ann Surg) Vol. 275 Issue 4 Pg. 692-699 (04 01 2022) ISSN: 1528-1140 [Electronic] United States
• PMID: 32482981 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Biomarkers
• Docetaxel
• RAD51 protein, human
• Rad51 Recombinase
• Cisplatin
• Fluorouracil

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers
• Carcinoma, Squamous Cell (surgery)
• Chemoradiotherapy
• Cisplatin (therapeutic use)
• Docetaxel (therapeutic use)
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma (therapy)
• Fluorouracil (therapeutic use)
• Humans
• Prognosis
• Rad51 Recombinase (therapeutic use)
• Treatment Outcome