犬淋巴瘤預後與CD10、Bcl-6、MUM1和Bcl-2表現之相關性

Abstract

淋巴瘤是犬最常見的惡性腫瘤之一，形態學上與人類非何杰金氏淋巴瘤 （non-Hodgkin’s lymphoma）具有高度類似性。依照世界衛生組織分類法，瀰漫性大型B細胞淋巴瘤（diffuse large B cell lymphoma; DLBCL）為犬最常見的淋巴瘤。此外，濾泡型淋巴瘤（follicular lymphoma）、被套細胞淋巴瘤（mantle cell lymphoma）、邊緣區型淋巴瘤（marginal zone lymphoma）、與T區域型淋巴瘤（T-zone lymphoma）之臨床表徵屬於緩慢型淋巴瘤（indolent lymphoma）。 DLBCL在人類可區分為類生發中心B細胞型（germinal center B-cell-like）與類活化B細胞型（activated B-cell-like）兩種分子學亞型（molecular subtypes），前者之生物標記包含了CD10和Bcl-6，而MUM1與Bcl-2則為後者之標記。病人罹患GCB型DLBCL具有顯著較佳總存活率。 本研究為探討在犬淋巴瘤中，這四個蛋白質之免疫組織化學染色表現程度與預後之相關性。在收集的102例病例中，B細胞淋巴瘤占59例、T細胞型占41例、以及無顯著分型之淋巴瘤占2例，其中DLBCL為最常見的淋巴瘤類型。針對具有完整臨床資訊之53病例，進行CD10、Bcl-6、MUM1和Bcl-2之免疫組織化學染色。結果顯示，Bcl-2表現弱之淋巴瘤具有顯著較短的總存活時間（overall survival time），而CD10、Bcl-6、MUM1之表現皆與預後無關。此外，本研究亦證實世界衛生組織分類法之診斷與預後有顯著相關，其中緩慢型淋巴瘤不但總存活時間較非緩慢型（non-indolent）淋巴瘤長，且皆具有中等至強的Bcl-2表現程度。本研究的結果顯示，犬DLBCL並無法以CD10、Bcl-6、MUM1和Bcl-2區分為不同的分子學亞型，然而在所有種類的淋巴瘤中，Bcl-2具有預估臨床預後之潛力，其機制仍需進一步的研究加以探討。

Lymphoma is one of the most common malignancies in dogs. Canine lymphoma bears a morphological resemblance to non-Hodgkin’s lymphoma in the human. Diffuse large B-cell lymphoma (DLBCL), according to the World Health Organization (WHO) classification, is the most common form of canine lymphoma. Furthermore, indolent lymphomas that are characterized by a slowly progressive clinical course include follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and T-zone lymphoma. Human DLBCLs can be sorted into two molecular subtypes: germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL. CD10 and Bcl-6 are biomarkers for GCB-DLBCL, while ABC-DLBCL is representative of MUM1 or Bcl-2 expression. Patients diagnosed with GCB-DLBCL show a significant better overall survival rate than those diagnosed with ABC-DLBCL. The present study is to investigate the correlation between prognosis and expression of CD10, Bcl-6, MUM1 and Bcl-2 in canine lymphomas. A total of 102 cases met the inclusion criteria, with 59 of B-cell derivation, 41 of T-cell derivation, and 2 of null-cell derivation. DLBCL was the most common diagnosis based on the WHO criteria. Immunohistochemical stain for CD10, Bcl-6, MUM1 and Bcl-2 was performed on a total of 53 cases with a complete medical and follow-up record. The results indicated that none of the markers had a correlation with prognosis with the exception of Bcl-2. Bcl-2 expression had a significantly positive correlation with overall survival time. Moreover, indolent lymphomas not only showed prolonged overall survival over non-indolent lymphomas, but also were characterized by moderate or strong levels of Bcl-2 expression. In conclusion, we did not find molecular subtypes of canine DLBCL via CD10, Bcl-6, MUM1 and Bcl-2 expression. Among these four markers, only Bcl-2 had a potential prognostic value of canine lymphomas. The mechanism of Bcl-2 remains to be determined, though.