Driscoll James J, Gauerke Steven, Monahan Brian C
Medical Oncology Branch, National Cancer Institute, Bethesda, Md., USA.
Case Rep Oncol. 2009 Mar 14;2(1):44-52. doi: 10.1159/000205351.
Hidradenocarcinomas are rare, aggressive adnexal tumors of sweat gland origin that demonstrate a high potential for local recurrence, metastasis and poor outcome. These neoplasms can derive from preexisting clear cell hidradenomas, but more commonly appear de novo with the molecular events responsible for the pathogenesis currently unknown. Molecular markers of pathogenesis as well as effective forms of adjuvant chemotherapy are missing due to the lack of accurate diagnosis, paucity of cases and confusion with other visceral solid tumors. Here, we report a 37-year-old man who presented with a rapidly growing, painful palpable mass located in the right inguinal area. The patient was a nonsmoker, did not consume alcohol and had a medical history remarkable only for a lower abdominal superficial skin lesion in the same area that had been excised 11 years earlier. Although initially slow growing, the lesion eventually expanded, was surgically excised and was diagnosed as a hidradenoma. There was no family history of malignancy and the patient had not experienced any constitutional symptoms. We probed the immunohistochemical status and detected negative staining for the estrogen, progesterone and Her2 receptors, while strong, diffuse nuclear staining was seen in the majority of cells consistent with p53 overexpression. Similarly, strong nuclear reactivity was seen with p63 and p73 antibodies. The p63 gene contains 2 separate promoters which express at least 6 major transcripts that lead to 2 fundamentally different classes of proteins; 3 isoforms (TAp63alpha, beta and gamma) encode proteins that induce apoptosis, whereas the other 3 isoforms (DeltaNp63alpha, beta and gamma) may exert inhibitory effects on p53. Interest in p63 stems from this 'two genes in one'-concept. Importantly, the nuclear presence of DeltaNp63 was detected widespread throughout the tumor. We have identified a subtype of hidradenocarcinomas that express DeltaNp63 and uncovered an unforeseen commonality with triple-negative breast tumors. To our knowledge, this is the first report of a sweat gland tumor that displayed expression of both DeltaNp63 and p73 and demonstrated a triple-negative receptor status. Such a link between 2 seemingly disparate tumor types indicates a mutual pathway of tumorigenesis and suggests the potential for common therapeutic regimens.
汗腺癌是一种罕见的、侵袭性的附属器肿瘤，起源于汗腺，具有局部复发、转移的高风险及不良预后。这些肿瘤可源自先前存在的透明细胞汗腺瘤，但更常见的是新发肿瘤，其发病机制中的分子事件目前尚不清楚。由于缺乏准确的诊断、病例稀少以及与其他内脏实体瘤混淆，发病机制的分子标志物以及辅助化疗的有效形式均未明确。在此，我们报告一名37岁男性，其右侧腹股沟区出现一个迅速增大、有压痛的可触及肿块。患者不吸烟、不饮酒，病史中仅11年前在同一区域有过一次下腹部浅表皮肤病变，已切除。尽管最初生长缓慢，但病变最终扩大，手术切除后诊断为汗腺瘤。患者无恶性肿瘤家族史，也未出现任何全身症状。我们检测了免疫组化状态，雌激素、孕激素和Her2受体染色均为阴性，而大多数细胞中可见强的、弥漫性核染色，与p53过表达一致。同样，p63和p73抗体也显示强核反应性。p63基因包含2个独立启动子，表达至少6种主要转录本，导致2类根本不同的蛋白质；3种异构体（TAp63α、β和γ）编码诱导细胞凋亡的蛋白质，而另外3种异构体（DeltaNp63α、β和γ）可能对p53发挥抑制作用。对p63的关注源于这种“一个基因两种功能”的概念。重要的是，在整个肿瘤中广泛检测到DeltaNp63的核内存在。我们鉴定出一种表达DeltaNp63的汗腺癌亚型，并发现其与三阴性乳腺癌存在意外的共性。据我们所知，这是首次报道汗腺肿瘤同时表达DeltaNp63和p73，并显示三阴性受体状态。这两种看似不同的肿瘤类型之间的这种联系表明了共同的肿瘤发生途径，并提示了共同治疗方案的可能性。
