Departments of Pathology, Epidemiology and Biostatistics, Gynaecology, and Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
Clin Cancer Res. 2012 Sep 1;18(17):4560-9. doi: 10.1158/1078-0432.CCR-11-2385. Epub 2012 Jul 3.
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.
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, microsatellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8, and FoxP3 expression were carried out.
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.
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.
与息肉状腺瘤相比，扁平腺瘤是结直肠腺瘤的一个亚组，其临床行为更具侵袭性。在此，我们旨在比较与腺瘤向癌进展最明显相关的分子变化之一，即染色体不稳定性，在扁平状和息肉状结直肠腺瘤之间。
使用高分辨率阵列比较基因组杂交平台，对 83 例扁平状和 35 例息肉状腺瘤连续系列进行 DNA 拷贝数改变分析、微卫星不稳定性（MSI）状态和腺瘤性息肉病基因（APC）基因突变分析。进行 CD3、CD8 和 FoxP3 表达的免疫组织化学染色。
两种表型的 DNA 拷贝数改变模式不同，扁平腺瘤中 5q14.3 和 5q15-q31.1 的缺失更为频繁，而息肉状腺瘤中 1p36.32-p35.3、10q25.3、17p12 和 18 号染色体的缺失更为频繁（错误发现率<0.2）。在一个扁平腺瘤中观察到 MSI。由于 5q15-q31.1 区域包含 APC 基因座，因此研究了 APC 突变状态，结果显示扁平腺瘤中 APC 突变的发生率明显较低（P=0.04）。最初探索 5q 缺失与炎症之间的可能关联表明，与息肉状腺瘤相比，肿瘤浸润淋巴细胞在扁平腺瘤的基质中更为丰富。
扁平状和息肉状腺瘤具有部分不同的染色体图谱，这与这些表型背后的生物学差异一致。与扁平腺瘤更特异的改变，特别是 5q 缺失，可能与炎症有关。
