SOX2, p53 boost progression prediction in Barrett's esophagus

Last Updated: 2015-09-15

By Anne Harding

NEW YORK (Reuters Health) - Patterns of SOX2 and p53 expression can better identify Barrett's esophagus (BE) patients' risk of neoplastic progression, according to new findings.

"This study demonstrates that the combined immunohistochemical detection of p53 (aberrant pattern) and SOX2 (loss) is instrumental to identify low-grade dysplasia more accurately, resulting in a better prediction of progression," Dr. Leendert H.H. Looijenga and Dr. Katharina Biermann, of Erasmus University Medical Center in Rotterdam, the Netherlands, two of the study authors, told Reuters Health by email.

While current guidelines recommend patients with BE have endoscopic surveillance to detect high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), the researchers wrote, histological diagnosis of low-grade dysplasia (LGD) remains the "only accepted predictor for neoplastic progression to date."

"Histological diagnosis of LGD has a low sensitivity and specificity, due to high inter-observer variation, even among expert pathologists," Dr. Looijenga and Dr. Biermann said.

While research has suggested that aberrant p53 expression could help improve prediction of neoplastic progression, they added, it is seen in just 40% of patients with progression to HGD or EAC.

To investigate expression of the transcription factor SOX2 as another biomarker for neoplastic progression, the researchers performed a case-control study in a prospective cohort of 720 BE patients. Paraffin material was available for 635 patients, who underwent more than 12,000 biopsies. Fifty-one of the patients had neoplastic progression, and were classified as cases, while the remaining patients served as controls. Follow-up lasted a median 6.9 years, according to the September 1 American Journal of Gastroenterology report.

Nuclear staining was homogenous for SOX2 in nondysplastic BE. However, patients with dysplastic BE showed progressive loss of SOX2 expression. Among biopsies without dysplasia, just 2% showed loss of SOX2, versus 28% of biopsies with LGD and 67% of biopsies with HGD or EAC. Loss of SOX2 expression was associated with an adjusted relative risk of 4.8 for neoplastic progression, after adjustment for gender, age, BE length, and esophagitis.

Positive predictive value was 16% for LGD only but increased to 56% for LGD plus loss of SOX2 and aberrent expression of p53.

Intraobserver agreement for expression of SOX2 was good, the researchers noted, making the biomarker clinically suitable as a predictor for neoplastic progression. They concluded, "Clinical application of these biomarkers in routine practice has the potential to improve cost-effectiveness of BE surveillance."

SOURCE: http://bit.ly/1NuM4XS

Am J Gastroenterol 2015.