TY - JOUR
T1 - Chromosome 5q Loss in Colorectal Flat Adenomas
AU - Voorham, Quirinus J. M.
AU - Carvalho, Beatriz
AU - Spiertz, Angela J.
AU - van Grieken, Nicole C T
AU - Mongera, Sandra
AU - Rondagh, Eveline J. A.
AU - van de Wiel, Mark A.
AU - Jordanova, Ekaterina S.
AU - Ylstra, Bauke
AU - Kliment, Martin
AU - Grabsch, Heike
AU - Rembacken, Bjorn J.
AU - Arai, Tomio
AU - de Bruine, Adriaan P.
AU - Sanduleanu, Silvia
AU - Quirke, Philip
AU - Mulder, Chris J. J.
AU - van Engeland, Manon
AU - Meijer, Gerrit A.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - Purpose: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared with their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas. Experimental Design: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution array comparative genomic hybridization platform, micro-satellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8, and FoxP3 expression were carried out. Results: Patterns of DNA copy number changes differed between the two phenotypes, with significantly more frequent loss of 5q14.3 and 5q15-q31.1 in flat adenomas, whereas losses of 1p36.32-p35.3, 10q25.3, 17p12, and chromosome 18 were more frequent in polypoid adenomas (false discovery rate <0.2). MSI was observed in one flat adenoma. As the 5q15-q31.1 region harbors the APC locus, APC mutation status was investigated, showing significantly less mutations in flat adenomas (P = 0.04). An initial exploration of a possible association of 5q loss with inflammation indicated that tumor-infiltrating lymphocytes were more abundant in the stroma of flat adenomas compared with that of polypoid adenomas. Conclusion: Flat and polypoid adenomas have partially distinct chromosomal profiles, consistent with differences in the biology underlying these phenotypes. Alterations more specific to flat adenomas, in particular 5q loss, may be associated with inflammation. Clin Cancer Res; 18(17); 4560-9.
AB - Purpose: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared with their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas. Experimental Design: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution array comparative genomic hybridization platform, micro-satellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8, and FoxP3 expression were carried out. Results: Patterns of DNA copy number changes differed between the two phenotypes, with significantly more frequent loss of 5q14.3 and 5q15-q31.1 in flat adenomas, whereas losses of 1p36.32-p35.3, 10q25.3, 17p12, and chromosome 18 were more frequent in polypoid adenomas (false discovery rate <0.2). MSI was observed in one flat adenoma. As the 5q15-q31.1 region harbors the APC locus, APC mutation status was investigated, showing significantly less mutations in flat adenomas (P = 0.04). An initial exploration of a possible association of 5q loss with inflammation indicated that tumor-infiltrating lymphocytes were more abundant in the stroma of flat adenomas compared with that of polypoid adenomas. Conclusion: Flat and polypoid adenomas have partially distinct chromosomal profiles, consistent with differences in the biology underlying these phenotypes. Alterations more specific to flat adenomas, in particular 5q loss, may be associated with inflammation. Clin Cancer Res; 18(17); 4560-9.
U2 - 10.1158/1078-0432.CCR-11-2385
DO - 10.1158/1078-0432.CCR-11-2385
M3 - Article
C2 - 22761468
SN - 1078-0432
VL - 18
SP - 4560
EP - 4569
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -