Abstract
This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.
Highlights
Uterine cervical cancer is the second most common cancer in women and the leading cause of cancer death in women in most developing countries [1]
21 patients with newly diagnosed AC of the uterine cervix were included in this study
The myeloid cell leukemia-1 (MCL1) copy number variation was calculated based on data from the 29 aforementioned samples in The Cancer Genome Atlas (TCGA)
Summary
Uterine cervical cancer is the second most common cancer in women and the leading cause of cancer death in women in most developing countries [1]. Adenocarcinoma (AC) of the uterine cervix constitutes approximately 10% to 20% of all cervical carcinomas with a trend toward a growing incidence [2,3]. Some studies have suggested that AC and squamous cell carcinoma (SCC) behave differently epidemiologically [2,3,4,5,6,7], and genomic differences exist [8,9]. AC patients have inferior outcomes after the same treatment [4,6,10,11,12,13]. Most treatment knowledge of cervical AC derives from studies where AC was present in a minority of patients. There is a need to advance molecular profiling of treatment strategies for AC
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