Shi Yun-fei, Liu Cui-ling, Zhou Chun-ju, Gong Li-ping, Dong Li-na, Li Min, Huang Xin, Gao Zi-fen
Department of Pathology, Peking University School of Basic Medical Sciences, Beijing, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2008 Aug 18;40(4):380-6.
To study the expression of anaplastic lymphoma kinase (ALK) and chromosome breakage of the anaplastic lymphoma kinase (ALK) gene retrospectively and to investigate their possible value as indicators of prognosis in primary systemic anaplastic large cell lymphomas (S-ALCL).
Twenty-eight cases of S-ALCL were collected from the Lymphoma Lab, the Department of Pathology, Peking University Health Science Center and Beijing Children's Hospital. The morphologic characteristics were studied under light microscope, and essential immunohistochemical staininings (IHC) were performed and reviewed to confirm the diagnosis of S-ALCL. ALK-1 monoclonal antibody was used to assess ALK fusion protein expression, and EnVision method was used in IHC. Locus specific interphase fluorescence in situ hybridization (LSI-FISH) was also performed on the neoplastic cells using paraffin-embedded tissues to detect ALK gene abnormality.
ALK-1 protein was expressed in 19 of the 28 cases. In 14 ALCL cases, ALK gene breakage was detected by LSI-FISH, using a dual-color break-apart ALK gene DNA (LSI-ALK) probe. Of the other 14 cases which did not show ALK gene breakage, 5 showed 2 copies of ALK gene as normal, and 9 showed multi-copies of ALK gene. Of all the 28 cases, 22 had complete follow-up materials. Sixteen survived and 6 died, their survival time ranged from 0.5 to 36.0 months, and the survival time on average was 12.8 months, cumulative proportion survival rate was 73.9% in the 1st year. Those cases showing multi-copies of ALK gene might have the worst outcome, with only 47.6% of cumulative proportion survival rate in the 1st year.
IHC detection for ALK fusion protein is important to the diagnosis of S-ALCL. ALK gene breakage detected by interphase LSI-FISH might not be always consistent with abnormal expression of ALK fusion protein. Complex abnormalities of ALK gene exist in S-ALCL cases, and different types of ALK gene might lead to different clinical outcome. Those cases with multi-copies of ALK gene probably have the poorest prognosis.
回顾性研究间变性淋巴瘤激酶（ALK）的表达及ALK基因的染色体断裂情况，并探讨其作为原发性系统性间变性大细胞淋巴瘤（S-ALCL）预后指标的可能价值。
从北京大学医学部病理学系淋巴瘤实验室及北京儿童医院收集28例S-ALCL病例。在光学显微镜下研究其形态学特征，并进行必要的免疫组织化学染色（IHC）以确诊S-ALCL。使用ALK-1单克隆抗体评估ALK融合蛋白的表达，免疫组织化学采用EnVision法。还使用石蜡包埋组织对肿瘤细胞进行位点特异性间期荧光原位杂交（LSI-FISH），以检测ALK基因异常。
28例中有19例表达ALK-1蛋白。在14例ALCL病例中，使用双色断裂分离ALK基因DNA（LSI-ALK）探针通过LSI-FISH检测到ALK基因断裂。在未显示ALK基因断裂的其他14例病例中，5例显示ALK基因2拷贝正常，9例显示ALK基因多拷贝。28例中22例有完整的随访资料。16例存活，6例死亡，生存时间为0.5至36.0个月，平均生存时间为12.8个月，第1年累积生存率为73.9%。显示ALK基因多拷贝的病例预后可能最差，第1年累积生存率仅为47.6%。
免疫组织化学检测ALK融合蛋白对S-ALCL的诊断很重要。间期LSI-FISH检测到的ALK基因断裂可能并不总是与ALK融合蛋白的异常表达一致。S-ALCL病例中存在ALK基因的复杂异常情况不同类型的ALK基因可能导致不同的临床结局。ALK基因多拷贝的病例预后可能最差。
