Clarke Loren E, Bayerl Michael G, Bruggeman Richard D, Mauger David, Ioffreda Michael D, Abou-Elella Ashraf, Helm Klaus F
Departments of Pathology, Penn State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Am J Surg Pathol. 2005 Apr;29(4):452-9. doi: 10.1097/01.pas.0000155154.46434.93.
The CD30-positive lymphoproliferative disorders lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and systemic anaplastic large cell lymphoma (S-ALCL) are lesions that overlap clinically, histopathologically, and immunophenotypically. Their biologic behaviors, however, vary considerably. In particular, lesions of LyP regress spontaneously while those of S-ALCL persist and often progress. Apoptosis has been suggested as the mechanism by which the lesions of LyP regress, but the underlying signaling pathways remain unclear. In this study, we used newly developed activation state-specific antibodies to demonstrate apoptosis signaling through the death receptor-mediated pathway regulated by FADD and caspase 3.
Dual immunohistochemistry for CD30 and activated forms of FADD and caspase 3 was performed on cutaneous biopsy specimens from 27 patients with CD30-positive lymphoproliferative disorders involving the skin. The patients included 18 with primary cutaneous CD30-positive LPDs (15 with LyP and 3 with C-ALCL) and 9 with S-ALCL.
The proportion of CD30-positive cells expressing activated FADD was significantly different between primary cutaneous CD30-positive lymphoproliferative disorders and S-ALCL (36.4% vs. 14.5%, P = 0.0083). Expression of cleaved caspase 3 was also significantly different between primary cutaneous lesions and S-ALCL (9.2% vs. 1.9%, P = 0.048).
Although a larger number of cases should be studied to validate these results, these data provide evidence that differences in signaling through the death-receptor apoptosis pathway mediated by FADD may be responsible for the varying biologic behaviors of CD30-positive lymphoproliferative disorders involving the skin.
CD30阳性淋巴增殖性疾病，包括淋巴瘤样丘疹病（LyP）、原发性皮肤间变性大细胞淋巴瘤（C-ALCL）和系统性间变性大细胞淋巴瘤（S-ALCL），在临床、组织病理学和免疫表型上存在重叠。然而，它们的生物学行为差异很大。特别是，LyP病变可自发消退，而S-ALCL病变持续存在且常进展。细胞凋亡被认为是LyP病变消退的机制，但其潜在的信号通路仍不清楚。在本研究中，我们使用新开发的激活状态特异性抗体来证明通过由FADD和半胱天冬酶3调节的死亡受体介导途径的凋亡信号传导。
对27例累及皮肤的CD30阳性淋巴增殖性疾病患者的皮肤活检标本进行CD30与激活形式的FADD和半胱天冬酶3的双重免疫组织化学检测。患者包括18例原发性皮肤CD30阳性淋巴增殖性疾病患者（15例LyP和3例C-ALCL）和9例S-ALCL患者。
原发性皮肤CD30阳性淋巴增殖性疾病与S-ALCL之间，表达激活FADD的CD30阳性细胞比例有显著差异（36.4%对14.5%，P = 0.0083）。原发性皮肤病变与S-ALCL之间，裂解的半胱天冬酶3的表达也有显著差异（9.2%对1.9%，P = 0.048）。
尽管需要研究更多病例来验证这些结果，但这些数据提供了证据，表明由FADD介导的死亡受体凋亡途径信号传导的差异可能是累及皮肤的CD30阳性淋巴增殖性疾病生物学行为不同的原因。
