Faraj Sheila F, Chaux Alcides, Gonzalez-Roibon Nilda, Munari Enrico, Cubilla Antonio L, Shih Ie-Ming, Netto George J
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231; Department of Scientific Research, Norte University, Asunción, 1614, Paraguay.
Hum Pathol. 2015 May;46(5):761-6. doi: 10.1016/j.humpath.2015.01.018. Epub 2015 Feb 12.
ARID1A, a member of the chromatin remodeling genes family, has been suggested as a novel tumor suppressor gene in gynecologic malignancies. However, its role in penile cancer has yet to be determined. This study assesses the immunohistochemical expression of ARID1A in penile squamous cell carcinoma (SCC) and its association with pathologic features, human papillomavirus (HPV) status, and previously reported mammalian target of rapamycin pathway markers in the same cohort. Four tissue microarrays were constructed from 112 cases of formalin-fixed, paraffin-embedded penile SCC from Paraguay. Each tumor was sampled 3 to 12 times. ARID1A expression was evaluated by immunohistochemistry using a polyclonal rabbit anti-ARID1A (BAF250A) antibody. An H score was calculated in each spot as the sum of expression intensity (0-3+) by extent (0%-100%). Median H score per case was used for statistical analysis. ARID1A expression was observed in all cases, ranging from 3% to 100% of tumor cells (median, 95%). In 96 cases (86%), ARID1A expression was observed in 90% or more tumor cells. HPV DNA was detected in 20 (38%) of 52 analyzed samples. There was a significant trend of association between ARID1A and histologic grade. ARID1A expression was not associated with histologic subtype (P = .61) or HPV status (P = .18). ARID1A expression decreased with decreasing levels of PTEN expression (P = .01). ARID1A was expressed in penile SCC, in most cases at high levels. A significant trend of association was found between histologic grade and ARID1A expression, with lower ARID1A expression, lower histologic grades, and decreased PTEN expression.
ARID1A是染色质重塑基因家族的成员之一,已被认为是妇科恶性肿瘤中的一种新型肿瘤抑制基因。然而,其在阴茎癌中的作用尚未确定。本研究评估了ARID1A在阴茎鳞状细胞癌(SCC)中的免疫组化表达及其与病理特征、人乳头瘤病毒(HPV)状态以及同一队列中先前报道的雷帕霉素哺乳动物靶标通路标志物的关联。从巴拉圭的112例福尔马林固定、石蜡包埋的阴茎SCC病例中构建了四个组织微阵列。每个肿瘤取样3至12次。使用兔抗ARID1A多克隆抗体(BAF250A)通过免疫组化评估ARID1A表达。在每个点计算H评分,即表达强度(0 - 3 +)乘以范围(0% - 100%)的总和。每个病例的H评分中位数用于统计分析。在所有病例中均观察到ARID1A表达,肿瘤细胞表达范围为3%至100%(中位数为95%)。在96例(86%)病例中,90%或更多肿瘤细胞中观察到ARID1A表达。在52个分析样本中的20个(38%)检测到HPV DNA。ARID1A与组织学分级之间存在显著的关联趋势。ARID1A表达与组织学亚型(P = 0.61)或HPV状态(P = 0.18)无关。ARID1A表达随PTEN表达水平降低而降低(P = 0.01)。ARID1A在阴茎SCC中表达,大多数情况下表达水平较高。在组织学分级与ARID1A表达之间发现了显著的关联趋势,ARID1A表达越低,组织学分级越低,PTEN表达降低。