Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/90938
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Type: Journal article
Title: Claudin-1 expression is elevated in colorectal cancer precursor lesions harboring the BRAF V600E mutation
Author: Caruso, M.
Fung, K.
Moore, J.
Brierley, G.
Cosgrove, L.
Thomas, M.
Cheetham, G.
Brook, E.
Fraser, L.
Tin, T.
Ha, T.
Ruszkiewicz, A.
Citation: Translational Oncology, 2014; 7(4):456-463
Publisher: Elsevier
Issue Date: 2014
ISSN: 1944-7124
1936-5233
Statement of
Responsibility: 
Maria Caruso, Kim Y.C. Fung, James Moore, Gemma V. Brierley, Leah J. Cosgrove, Michelle Thomas, Glenice Cheetham, Emma Brook, Louise M. Fraser, Teresa Tin, Ha Tran, Andrew Ruszkiewicz
Abstract: BACKGROUND: Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P and microvesicular hyperplastic polyps (MVHP) is challenging and may not be possible in routine practice. METHODS: Gene expression profiling of MVHP (n=5, all BRAF V600E wild-type) and SSA/P (n=5, all BRAF V600E mutant) samples was performed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical analysis was performed to verify the expression of claudin 1 (CLDN1) in MVHP and SSA/P. RESULTS: Gene expression profiling studies conducted between MVHP and SSA/P identified CLDN1 as the most statistically significant differentially expressed gene (p<0.05). Validation with qRT-PCR confirmed an up-regulation of CLDN1 in BRAF V600E mutant polyps regardless of polyp type (p<0.0005). Immunohistochemical analysis of CLDN1 expression in BRAF V600E mutant SSA/Ps (n=53) and MVHPs (n=111) and BRAF wild-type MVHPs (n=58), demonstrated a strong correlation between CLDN1 expression and the BRAF V600E mutation in both SSA/P and MVHP samples when compared to wild-type polyps (p<0.0001). CONCLUSION: This study demonstrates an up regulation of CLDN1 protein in serrated colorectal polyps including MVHP harbouring the BRAF V600E mutation. Our results demonstrated an apparent heterogeneity on the molecular level within the MVHP group and suggest that MVHP with somatic BRAF V600E mutation and up-regulated expression of CLDN1 are closely related to SSA/P and may in fact represent a continuous spectrum of the same neoplastic process within the serrated pathway of colorectal carcinogenesis.
Rights: © 2014 Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
RMID: 0030023833
DOI: 10.1016/j.tranon.2014.05.009
Grant ID: http://purl.org/au-research/grants/nhmrc/1012157
Appears in Collections:Medicine publications

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