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

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

Journal

Annals of surgery

ISSN: 1528-1140

Titre abrégé: Ann Surg

Pays: United States

ID NLM: 0372354

Informations de publication

Date de publication:
01 04 2022

Historique:

pubmed: 3 6 2020

medline: 27 4 2022

entrez: 3 6 2020

Statut: ppublish

Résumé

The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1097/SLA.0000000000003975 PMID: 32482981

pubmed: 32482981

pii: 00000658-202204000-00013

doi: 10.1097/SLA.0000000000003975

doi:

Substances chimiques

Biomarkers 0

Docetaxel 15H5577CQD

RAD51 protein, human EC 2.7.7.-

Rad51 Recombinase EC 2.7.7.-

Cisplatin Q20Q21Q62J

Fluorouracil U3P01618RT

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

692-699

Informations de copyright

Déclaration de conflit d'intérêts

The authors report no conflicts of interest.

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