Over-expression of cathepsin E and trefoil factor 1 in sessile serrated adenomas of the colorectum identified by gene expression analysis

Autor: Nancy Lerda, Glenice Cheetham, Anna Tyskin, Stuart Phillis, Michelle L Thomas, Andrew Ruszkiewicz, Gregory J. Goodall, James Moore, Maria Gabriella Caruso, Hiroyuki Takahashi
Přispěvatelé: Caruso, Maria, Moore, James, Goodall, Gregory J, Thomas, Michelle, Phillis, Stuart, Tyskin, Anna, Cheetham, Glenice, Lerda, Nancy, Takahashi, Hiroyuki, Ruszkiewicz, Andrew
Rok vydání: 2009
Předmět:
Male
Pathology
endocrine system diseases
Colorectal cancer
cathepsin E
Gene Expression
Cathepsin E
medicine.disease_cause
serrated neoplasia pathway
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
trefoil factor 1
Intestinal Polyps
General Medicine
Immunohistochemistry
Up-Regulation
KRAS Mutation Analysis
Female
Trefoil Factor-1
KRAS
Colorectal Neoplasms
Adenoma
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
colorectal cancer
Biology
Pathology and Forensic Medicine
Proto-Oncogene Proteins p21(ras)
Proto-Oncogene Proteins
Biomarkers
Tumor
medicine
Humans
neoplasms
Molecular Biology
Aged
Tumor Suppressor Proteins
Cell Biology
medicine.disease
digestive system diseases
stomatognathic diseases
Hyperplastic Polyp
sessile serrated adenoma
Mutation
ras Proteins
gene expression
Precancerous Conditions
V600E
Sessile serrated adenoma
Zdroj: Virchows Archiv. 454:291-302
ISSN: 1432-2307
0945-6317
DOI: 10.1007/s00428-009-0731-0
Popis: Sessile serrated adenomas are now recognised as precursor lesions of a substantial subset of colorectal cancers arising via a so-called "serrated pathway". However, their biological markers remain to be defined. The aim of our study was to identify differentially expressed genes in sessile serrated adenomas and conventional adenomas. Gene expression analysis demonstrated molecular differences between polyp types. Further studies using quantitative real-time polymerase chain reaction on cathepsin E (CTSE) demonstrated a significantly (p < 0.05) higher expression in sessile serrated adenomas as compared to hyperplastic polyp and tubular adenomas. Trefoil Factor 1 showed the same trend of expression for sessile serrated adenomas as compared to hyperplastic polyps and was significantly higher in both polyps compared to tubular adenomas. Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining of abnormal crypts in all sessile serrated adenomas, while staining in tubular adenomas and hyperplastic polyps was absent or weak and focal. BRAF and KRAS mutation analysis were employed to further validate polyp discrimination. The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (p < 0.05). This study demonstrates the over-expression in CTSE, in particular, and TFF1 in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas. Refereed/Peer-reviewed
Databáze: OpenAIRE
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