Inamura Kentaro, Kobayashi Maki, Nagano Hiroko, Sugiura Yoshiya, Ogawa Masahiro, Masuda Hitoshi, Yonese Junji, Ishikawa Yuichi
Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
Hum Pathol. 2017 Nov;69:96-100. doi: 10.1016/j.humpath.2017.04.022. Epub 2017 May 10.
Here, we report an inflammatory myofibroblastic tumor (IMT) of the urinary bladder with a novel HNRNPA1-ALK fusion. To the best of our knowledge, this is the first case of a tumor with HNRNPA1-ALK fusion. A 42-year-old Japanese man underwent total cystectomy because of an invasive urinary bladder tumor. Grossly, the tumor had invaded the peribladder fat tissue. Histologically, it comprised spindle neoplastic cells with intermingled inflammatory cells. Immunohistochemically, it was positive for ALK, SMA, desmin, cytokeratin, and vimentin, consistent with the immunohistochemical characteristics of IMTs. Fluorescence in situ hybridization demonstrated an ALK split, and the presence of HNRNPA1-ALK was revealed by RNA sequencing. We identified a novel transcript fusion of exon 2 of HNRNPA1 and exon 18 of ALK, resulting in ALK protein overexpression. These findings provide useful information on the biology and tumorigenesis of IMTs, thus facilitating the development of molecular-targeted therapeutics.
在此，我们报告一例具有新型HNRNPA1-ALK融合的膀胱炎性肌纤维母细胞瘤（IMT）。据我们所知，这是首例具有HNRNPA1-ALK融合的肿瘤病例。一名42岁的日本男性因浸润性膀胱肿瘤接受了全膀胱切除术。大体上，肿瘤侵犯了膀胱周围脂肪组织。组织学上，它由梭形肿瘤细胞和散在的炎性细胞组成。免疫组化显示，其ALK、平滑肌肌动蛋白（SMA）、结蛋白、细胞角蛋白和波形蛋白呈阳性，与IMT的免疫组化特征一致。荧光原位杂交显示ALK基因分离，RNA测序揭示了HNRNPA1-ALK的存在。我们鉴定出HNRNPA1第2外显子与ALK第18外显子的新型转录本融合，导致ALK蛋白过表达。这些发现为IMT的生物学特性和肿瘤发生提供了有用信息，从而有助于分子靶向治疗药物的开发。
