Went Philip, Agostinelli Claudio, Gallamini Andrea, Piccaluga Pier Paolo, Ascani Stefano, Sabattini Elena, Bacci Francesco, Falini Brunangelo, Motta Teresio, Paulli Marco, Artusi Tullio, Piccioli Milena, Zinzani Pier Luigi, Pileri Stefano A
Institute of Hematology and Clinical Oncology L. and A. Seràgnoli, Hematology and Hematopathology Units, St Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
J Clin Oncol. 2006 Jun 1;24(16):2472-9. doi: 10.1200/JCO.2005.03.6327. Epub 2006 Apr 24.
Although peripheral T-cell lymphoma, unspecified (PTCL/U), is the most common T-cell tumor in Western countries, no study to date has been based on the application of a wide panel of markers to a large series of patients and assessed the impact of phenotype on survival. We evaluated the expression of 19 markers in 148 PTCLs/U and 45 PTCLs of the angioimmunoblastic type (AILD).
The analysis was performed on tissue microarrays by immunohistochemistry and in situ hybridization. Clinical data were available in 93 PTCL/U patients, most of whom had been included in a previous study proposing a prognostic index (PIT).
An aberrant phenotype with frequent loss of CD5 and/or CD7 was typical for PTCLs, irrespective of whether they were U or AILD. Aberrantly expressed proteins rarely included CD20, CD15, and CD30. Positivity for Epstein-Barr virus-associated small RNAs and CD15 expression emerged as adverse prognostic factors. Among PTCLs/U, the proliferation-associated protein Ki-67 turned out to be prognostically relevant and was integrated in a new predictive score, incorporating age (> 60 years), high lactate dehydrogenase, poor performance status, and Ki-67 > or = 80%. This score was associated with the patient outcome (P < .0001) and was found to be more robust than PIT (P = .0043) in the present series.
Our retrospective analysis shows a wide range of protein expression in PTCLs and proposes a new prognostic index. The latter represents one of the first examples of mixed score (including patient- and tumor-specific factors) applied to malignant lymphomas and may be the basis for future prospective therapeutic trials.
尽管外周T细胞淋巴瘤,非特指型(PTCL/U)是西方国家最常见的T细胞肿瘤,但迄今为止尚无研究基于对大量患者应用多种标志物并评估表型对生存的影响。我们评估了19种标志物在148例PTCL/U和45例血管免疫母细胞型(AILD)PTCL中的表达情况。
通过免疫组织化学和原位杂交在组织芯片上进行分析。93例PTCL/U患者有临床数据,其中大多数已纳入先前一项提出预后指数(PIT)的研究。
无论PTCL是U型还是AILD型,异常表型伴CD5和/或CD7频繁缺失是其典型特征。异常表达的蛋白很少包括CD20、CD15和CD30。爱泼斯坦-巴尔病毒相关小RNA阳性和CD15表达是不良预后因素。在PTCL/U中,增殖相关蛋白Ki-67被证明具有预后相关性,并被纳入一个新的预测评分中,该评分纳入了年龄(>60岁)、高乳酸脱氢酶、较差的体能状态以及Ki-67≥80%。该评分与患者预后相关(P<.0001),并且在本系列研究中发现其比PIT更可靠(P=.0043)。
我们的回顾性分析显示PTCL中存在广泛的蛋白表达,并提出了一个新的预后指数。后者是应用于恶性淋巴瘤的混合评分(包括患者和肿瘤特异性因素)的首批实例之一,可能是未来前瞻性治疗试验的基础。