Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp

David Hernandez Gonzalo, Keith K. Lai, Bonnie Shadrach, John R. Goldblum, Ana E. Bennett, Erinn Downs-Kelly, Xiuli Liu, Walter Henricks, Deepa T. Patil, Paula Carver, Jie Na, Banu Gopalan, Lisa Rybicki, Rish Pai

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer-related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73% and a specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer-related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalJournal of Pathology
Volume230
Issue number4
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

Annexins
antineoplaston A10
Gene Expression Profiling
Polyps
Adenoma
Colon
Gene Expression
Colonic Neoplasms
Polymerase Chain Reaction
Microsatellite Instability
Neoplasm Genes
Microarray Analysis
Transcriptome

Keywords

  • annexin A10
  • colon cancer
  • hyperplastic polyp
  • sessile serrated polyp/adenoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. / Gonzalo, David Hernandez; Lai, Keith K.; Shadrach, Bonnie; Goldblum, John R.; Bennett, Ana E.; Downs-Kelly, Erinn; Liu, Xiuli; Henricks, Walter; Patil, Deepa T.; Carver, Paula; Na, Jie; Gopalan, Banu; Rybicki, Lisa; Pai, Rish.

In: Journal of Pathology, Vol. 230, No. 4, 01.08.2013, p. 420-429.

Research output: Contribution to journalArticle

Gonzalo, DH, Lai, KK, Shadrach, B, Goldblum, JR, Bennett, AE, Downs-Kelly, E, Liu, X, Henricks, W, Patil, DT, Carver, P, Na, J, Gopalan, B, Rybicki, L & Pai, R 2013, 'Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp', Journal of Pathology, vol. 230, no. 4, pp. 420-429. https://doi.org/10.1002/path.4200
Gonzalo, David Hernandez ; Lai, Keith K. ; Shadrach, Bonnie ; Goldblum, John R. ; Bennett, Ana E. ; Downs-Kelly, Erinn ; Liu, Xiuli ; Henricks, Walter ; Patil, Deepa T. ; Carver, Paula ; Na, Jie ; Gopalan, Banu ; Rybicki, Lisa ; Pai, Rish. / Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. In: Journal of Pathology. 2013 ; Vol. 230, No. 4. pp. 420-429.
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abstract = "Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer-related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73{\%} and a specificity of 95{\%} in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer-related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer.",
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AU - Gonzalo, David Hernandez

AU - Lai, Keith K.

AU - Shadrach, Bonnie

AU - Goldblum, John R.

AU - Bennett, Ana E.

AU - Downs-Kelly, Erinn

AU - Liu, Xiuli

AU - Henricks, Walter

AU - Patil, Deepa T.

AU - Carver, Paula

AU - Na, Jie

AU - Gopalan, Banu

AU - Rybicki, Lisa

AU - Pai, Rish

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