目的:腺癌是一种向汗腺导管上部分化的恶性汗腺肿瘤,可能是由先前存在的良性口腔癌的转化引起的。2019年,Sekine等人。证明YAP1::MAML2和YAP1::NUTM1融合存在于大多数孔瘤和孔瘤中。最近,我们的研究小组在一部分良性孔瘤中发现了PAK2融合.在此,我们报告了一系列12例携带PAK1/2/3融合的腺癌病例。
结果:5例患者为男性,中位年龄为79岁(范围:59-95)。肿瘤位于躯干(n=7),大腿上(n=3),颈部(n=1),或腹股沟面积(n=1)。4例患者发生远处转移。微观上,七例病例中含有良性孔瘤成分和恶性浸润性部分。全部观察到导管形成,而在七个和六个肿瘤中检测到漏斗/角囊肿和具有空泡质的细胞,分别。在三种情况下,侵袭性成分由细长细胞的增殖组成,其中一些形成了假血管空间,而其他人则具有主要的固体或小梁生长模式。CEA和EMA的免疫组织化学染色证实了导管的存在。在三个标本中检测到局灶性雄激素受体表达。全RNA测序证明LAMTOR1::PAK1(n=2),ZDHHC5::PAK1(n=2),DLG1::PAK2、CTDSP1::PAK1、CTNND1::PAK1、SSR1::PAK3、CTNNA1:::PAK2、RNF13:::PAK2、ROBO1::PAK2和CD47::PAK2。HRAS的激活突变(G13V,n=3,G13R,n=1,Q61L,n=2)存在于六个病例中。
结论:我们的研究表明,PAK1/2/3融合是缺乏YAP1重排的一组胃癌的致癌驱动因素。
OBJECTIVE: Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.
RESULTS: Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.
CONCLUSIONS: Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.