Molecular biology of squamous cell carcinoma of the anus: A comparison of HIV-positive and HIV-negative patients
Molecular biology of squamous cell carcinoma of the anus: A comparison of HIV-positive and HIV-negative patients
复制标题
DOI：
10.1016/j.gassur.2004.08.013
复制
发表时间：
2004-12-01
影响因子：
3.2
通讯作者：
Thibodeau, SN
中科院分区：
文献类型：
--
作者：
Gervaz, P;Hahnloser, D;Thibodeau, SN
参与肛门鳞状细胞癌（SCCA）进展的分子机制以及HIV感染的潜在作用尚不清楚。杂合性丢失（洛）是肿瘤抑制基因失活的机制之一。我们假设HIV诱导的免疫抑制可能通过肛管内人乳头瘤病毒感染的持续存在，导致SCCA进展的另一种分子途径。本研究旨在比较HIV阳性（HIV+）和HIV阴性（HIV-）患者中SCCA的分子生物学。我们从两个机构中诊断为SCCA的18名HIV-和10名HIV+患者中检索肿瘤标本。提取肿瘤组织和正常组织的DNA，然后用聚合酶链反应扩增。共检测到14个位点的洛缺失：18 q（DCC）3个，13 q（Rb）2个，17 p（p53）3个，11 q 3个，2 p 1个，5 q（APC）2个。洛缺失定义为肿瘤DNA与正常组织DNA的比值>2。HIV阳性患者更年轻（36 +/- 7岁vs 53 +/- 13岁，P = 0.001），并显示出肿瘤更大的趋势（3.7 +/- 1.6 cm vs 2.6 +/- 1.5 cm，P = 0.09）。诊断时HIV阳性患者的中位CD 4+计数为74 × 10（6）/L（范围，5 - 900）。总的洛频率为17.3%（236个信息位点中有41个洛）。HIV-患者的肿瘤比HIV+患者的肿瘤更容易出现洛缺失（24.1%对6.6%，P = 0.0004）。在特定位点也观察到两组之间等位基因丢失的差异，如18 q（41% [HIV-] vs 0% [HIV+]，P = 0.05），17 p（43% vs 10%，P = 0.09）和5 q（33% vs 0%，P = 0.12）。在SCCA的HIV患者中观察到染色体17 p、18 q、5 q和11 q上一致的洛缺失。相比之下，17 p、5 q和18 q的等位基因丢失在HIV+个体的肿瘤中似乎很少见。这些数据表明，免疫抑制可能通过替代途径促进SCCA进展，肛管内HPV感染的持续性可能在此过程中发挥核心作用。(C)2004年，消化道外科学会。
The molecular mechanisms involved in progression of squamous cell carcinoma of the anus (SCCA) are poorly elucidated, as well as the potential role of HIV infection. Loss of heterozygosity (LOH) is one of the mechanisms responsible for inactivation of tumor suppressor genes. We hypothesized that HIV-induced immunosuppression may contribute to an alternate molecular pathway in SCCA progression, through persistence of human papillomavirus infection within the anal canal. This study was undertaken to compare the molecular biology of SCCA in HIV-positive (HIV+) and HIV-negative (HIV-) patients. We retrieved tumor specimens from 18 HIV- and 10 HIV+ patients diagnosed with SCCA in two institutions. DNA from tumor and normal tissues was extracted and then amplified by polymerase chain reaction. LOH was investigated at 14 loci: three at 18q (DCC), two at 13q (Rb), three at 17p (p53), three at 11q, one at 2p, and two at 5q (APC). LOH was defined by a tumor DNA-to-normal tissue DNA ratio of >2. HIV+ patients were younger (36 +/- 7 years versus 53 +/- 13 years, P = 0.001) and showed a trend toward tumors of larger size (3.7 +/- 1.6 cm versus 2.6 +/- 1.5 cm, P = 0.09). The median CD4+ count in HIV+ patients at the time of diagnosis was 74 x 10(6)/L (range, 5 - 900). The overall frequency of LOH was 17.3% (41 LOH of 236 informative loci). Tumors in HIV- patients were more likely to present LOH than were tumors in HIV+ patients (24.1% versus 6.6%, P = 0.0004). Differences between the two groups with regard to allelic losses were also observed at specific loci, such as 18q (41% [HIV-] versus 0% [HIV+], P = 0.05), 17p (43% versus 10%, P = 0.09), and 5q (33% versus 0%, P = 0.12). Consistent LOH on chromosomes 17p, 18q, 5q, and 11q were observed in HIV- patients with SCCA. By contrast, allelic losses at 17p, 5q, and 18q seem to be rare in tumors of HIV+ individuals. These data suggest that immunosuppression may promote SCCA progression through an alternate pathway and that persistence of HPV infection within the anal canal may play a central role in this process. (C) 2004 The Society for Surgery of the Alimentary Tract.