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- Title
PIK3CA mutation is a favorable prognostic factor in esophageal cancer: molecular profile by next-generation sequencing using surgically resected formalin-fixed, paraffin-embedded tissue.
- Authors
Yokota, Tomoya; Serizawa, Masakuni; Hosokawa, Ayumu; Kusafuka, Kimihide; Mori, Keita; Sugiyama, Toshiro; Tsubosa, Yasuhiro; Koh, Yasuhiro
- Abstract
<bold>Background: </bold>Practical and reliable genotyping procedures with a considerable number of samples are required not only for risk-adapted therapeutic strategies, but also for stratifying patients into future clinical trials for molecular-targeting drugs. Recent advances in mutation testing, including next-generation sequencing, have led to the increased use of formalin-fixed paraffin-embedded tissue. We evaluated gene alteration profiles of cancer-related genes in esophageal cancer patients and correlated them with clinicopathological features, such as smoking status and survival outcomes.<bold>Methods: </bold>Surgically resected formalin-fixed, paraffin-embedded tissue was collected from 135 consecutive patients with esophageal cancer who underwent esophagectomy. Based on the assessment of DNA quality with a quantitative PCR-based assay, uracil DNA glycosylase pretreatment was performed to ensure quality and accuracy of amplicon-based massively parallel sequencing. Amplicon-based massively parallel sequencing was performed using the Illumina TruSeq® Amplicon Cancer Panel. Gene amplification was detected by quantitative PCR-based assay. Protein expression was determined by automated quantitative fluorescent immunohistochemistry.<bold>Results: </bold>Data on genetic alterations were available for 126 patients. The median follow-up time was 1570 days. Amplicon-based massively parallel sequencing identified frequent gene alterations in TP53 (66.7%), PIK3CA (13.5%), APC (10.3%), ERBB4 (7.9%), and FBXW7 (7.9%). There was no association between clinicopathological features or prognosis with smoking status. Multivariate analyses revealed that the PIK3CA mutation and clinical T stage were independent favorable prognostic factors (hazard ratio 0.34, 95% confidence interval: 0.12-0.96, p = 0.042). PIK3CA mutations were significantly associated with APC alterations (p = 0.0007) and BRAF mutations (p = 0.0090).<bold>Conclusions: </bold>Our study provided profiles of cancer-related genes in Japanese patients with esophageal cancer by next-generation sequencing using surgically resected formalin-fixed, paraffin-embedded tissue, and identified the PIK3CA mutation as a favorable prognosis biomarker.
- Subjects
GENETIC mutation; ESOPHAGEAL atresia; ESOPHAGEAL cancer; DNA; IMMUNOHISTOCHEMISTRY; DIGESTIVE organ surgery; ESOPHAGEAL tumors; FORMALDEHYDE; GENES; HISTOLOGICAL techniques; PEPTIDES; PROGNOSIS; PROTEINS; RESEARCH funding; SMOKING; TRANSFERASES; TUMOR classification; TISSUE arrays; SEQUENCE analysis
- Publication
BMC Cancer, 2018, Vol 18, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-018-4733-7