Elsevier

Surgery

Volume 138, Issue 4, October 2005, Pages 701-707
Surgery

Central Surgical Association
Survivin, a potential biomarker in the development of Barrett's adenocarcinoma

https://doi.org/10.1016/j.surg.2005.06.051Get rights and content

Background

Survivin, a member of the inhibitor-of-apoptosis family, is reported to be overexpressed in esophageal cancer but no data are available about its status in the metaplastic/dysplastic sequence. The aim of this study was to measure survivin gene expression in normal squamous/columnar epithelium and in the various stages of development of Barrett's adenocarcinoma.

Methods

Endoscopic biopsy or operative specimen samples from 5 tissue types were analyzed: (1) squamous epithelium from 3 cm above the gastroesophageal junction in patients with a negative pH study and no histologic injury (n = 17, pH- control); (2) antral tissue from patients with no evidence of Barrett's, dysplasia, or cancer (n = 29, antral control); (3) specialized intestinal metaplasia from patients with Barrett's esophagus (n = 16; Barrett's group); (4) low- or high-grade dysplasia (n = 12, dysplasia group), and (5) adenocarcinoma (n = 45 cancer group). After laser-capture microdissection cellular RNA was extracted from each tissue and reverse transcribed to complementary DNA. Expression levels of survivin were measured by reverse-transcription polymerase chain reaction.

Results

Survivin gene expression was greater in columnar (antral) compared with squamous (pH-) control tissues (P = .03). Expression in quiescent Barrett's epithelium was similar to both control tissues. Expression levels in dysplastic epithelium were greater than in squamous control (P = .01) and Barrett's tissues (P = .04), but not higher than columnar control tissues, whereas expression in adenocarcinoma was greater than all tissues except dysplasia (P < .001).

Conclusions

Survivin expression may be a biomarker in the development of Barrett's adenocarcinoma that is able to distinguish between quiescent Barrett's, dysplastic Barrett's, and Barrett's adenocarcinoma.

Section snippets

Tissue samples for semiquantitative real-time PCR

Tissue samples (n = 142) were obtained from endoscopy or operative specimens from 100 patients with foregut symptoms and were snap-frozen immediately in liquid nitrogen. Samples containing Barrett's metaplasia, dysplasia (high- or low-grade), or cancer were separated into 3 different groups based on routine histology: (1) Barrett's group: 23 samples from 16 patients showing intestinal metaplasia; (2) dysplasia group: 18 samples from 12 patients showing intestinal metaplasia and either low- (n =

Results

The study population included 29 women and 71 men. The median age of the patients was 57 years (range, 23-86 y). The median value and range of expression levels of survivin determined by semiquantitative reverse-transcription PCR analysis of the 5 tissue groups are listed in Table II (142 tissue samples from 100 patients) and shown in the figure.

Survivin gene expression levels differed among all histologic groups analyzed (P < .001). Survivin mRNA levels were lowest in squamous epithelium from

Discussion

The balance between cell division and cell loss is important for the maintenance of normal human tissue. An imbalance promoting either increased proliferation and/or decreased cell loss results in the uncontrolled cell growth characteristic of carcinogenesis. Recent studies have shown that the deregulation of apoptosis is an essential event in the development of Barrett's-associated adenocarcinoma and that the anti-apoptotic gene survivin is upregulated in esophageal cancer.3, 6, 7, 8, 9, 10

References (19)

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Presented at the 62nd Annual Meeting of the Central Surgical Association, Tucson, Arizona, March 10-15, 2005.

Supported by National Institutes of Health grants RO1-CA84424-02.

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