Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW 2065, Australia; Department of Anatomical Pathology, Sydpath, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW 2065, Australia; Histopath Pathology, North Ryde, NSW 2113, Australia; Sydney Medical School, University of Sydney 2050, NSW, Australia.
Hum Pathol. 2014 Aug;45(8):1697-703. doi: 10.1016/j.humpath.2014.04.009. Epub 2014 Apr 24.
ARID1A is a tumor suppressor gene involved in chromatin remodelling. ARID1A mutations and loss of protein expression occur commonly in endometrioid and gynecological clear cell carcinoma where they are associated with mismatch repair (MMR) deficiency. We assessed ARID1A expression in a large cohort of colorectal carcinomas (CRCs). Immunohistochemistry for ARID1A was performed on whole sections from 100 CRCs and on 1876 CRCs in tissue microarray format. There was complete concordance between the staining on whole slides and tissue microarray sections. Loss of staining was found in 110 (5.9%) of 1876 CRCs and was strongly associated with older age, right sided location, large size, BRAF V600E mutation, MMR deficiency, high histological grade and medullary morphology, (all P < .01). There was a trend towards loss of expression being more common in females (P = .06). When subclassified by combined BRAF V600E mutation and MMR status, loss of ARID1A expression was found most commonly in CRCs with the BRAF V600E mutated, MMR- deficient phenotype (58 of 232 cases, 25%, P < .01). In univariate and multivariate analysis, loss of ARID1A expression was not associated with overall survival-hazard ratio 1.05 (0.68-1.64) and 0.60 (0.24-1.44), respectively. All carcinomas arising in patients with known Lynch syndrome (n = 12) were ARID1A positive. We conclude that loss of ARID1A expression occurs in a small but significant proportion of CRCs where it is strongly correlated with mismatch repair deficiency and other clinical and pathological features associated with somatic hypermethylation.
ARID1A 是一种参与染色质重塑的肿瘤抑制基因。ARID1A 突变和蛋白表达缺失在子宫内膜样和妇科透明细胞癌中很常见，并且与错配修复（MMR）缺陷相关。我们评估了 ARID1A 在大量结直肠癌（CRC）病例中的表达。对 100 例 CRC 的全切片和组织微阵列格式的 1876 例 CRC 进行了 ARID1A 的免疫组织化学染色。全切片和组织微阵列切片上的染色完全一致。在 1876 例 CRC 中有 110 例（5.9%）存在染色缺失，并且与年龄较大、右侧位置、较大尺寸、BRAF V600E 突变、MMR 缺陷、高组织学分级和髓样形态强烈相关（所有 P <.01）。在女性中，表达缺失更为常见（P =.06）。当按 BRAF V600E 突变和 MMR 状态联合分类时，在具有 BRAF V600E 突变、MMR 缺陷表型的 CRC 中发现 ARID1A 表达缺失最为常见（232 例中有 58 例，25%，P <.01）。在单变量和多变量分析中，ARID1A 表达缺失与总生存无关 - 风险比为 1.05（0.68-1.64）和 0.60（0.24-1.44）。已知存在 Lynch 综合征的患者中所有发生的癌（n = 12）均为 ARID1A 阳性。我们的结论是，ARID1A 表达缺失发生在一小部分 CRC 中，但与 MMR 缺陷以及与体细胞过度甲基化相关的其他临床和病理特征密切相关。
