Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis.

Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis.
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非磷酸β-catenin的免疫组织化学染色是针对腹膜外脱乳突型纤维瘤病患者的COX-2抑制剂治疗的诊断和预后工具。

DOI:
10.1186/s13000-017-0654-z
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发表时间:
2017-08-29
影响因子:
2.6
通讯作者:
Ishiguro N
Ishiguro N
中科院分区:
医学4区
文献类型:
--
作者:
Sakai T;Nishida Y;Hamada S;Koike H;Ikuta K;Ota T;Ishiguro N

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传统的抗β-catenin抗体免疫组化染色已被应用于韧带样型纤维瘤病(DF)的诊断工具。本研究旨在评价抗非磷酸化β-catenin抗体免疫组化染色对DF的诊断和预后价值,与常规抗β-catenin抗体相比,其可能更准确地反映DF的侵袭性。2003年至2015年,40例腹膜外散发性DF患者前瞻性接受美洛昔康或塞来昔布(一种考克斯-2抑制剂)治疗。根据实体瘤疗效评价标准(RECIST)评价该治疗的疗效。对福尔马林固定的材料进行免疫组织化学染色以评估β-catenin和非磷酸化β-catenin的表达,并将阳性分组为阴性、弱、中等和强。从冷冻组织或福尔马林固定的材料中分离DNA,并通过直接测序确定CTNNB 1突变状态。在接受考克斯-2抑制剂治疗的40例患者中,1例完全缓解,12例部分缓解,7例病情稳定,20例病情进展。CTNNB 1突变位点在40例中有22例(55%)被检测到:T41 A(17例)、S45 F(3例)、T41 I和S45 P(各1例)。非磷酸化β-连环蛋白的阳性核表达与桑格法检测到的CTNNB 1阳性突变状态显着相关(p = 0.025),且考克斯-2抑制剂治疗的结局较差(p = 0.022)。相比之下,β-连环蛋白的核表达与CTNNB 1突变状态(p = 0.43)或考克斯-2抑制剂治疗的结果(p = 0.38)均无显著相关性。非磷酸化β-catenin的核表达可能更能反映DF的生物学行为,非磷酸化β-catenin的免疫组化染色可作为DF患者考克斯-2抑制剂治疗的更有用的诊断和预后工具。
Immunohistochemical staining with conventional anti-β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical staining with anti-non-phospho β-catenin antibody, which might more accurately reflect the aggressiveness of DF, in comparison to the conventional anti-β-catenin antibody. Between 2003 and 2015, 40 patients with extra-peritoneal sporadic DF were prospectively treated with meloxicam or celecoxib, a COX-2 inhibitor, therapy. The efficacy of this treatment was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Immunohistochemical staining was performed on formalin-fixed material to evaluate the expression of β-catenin and non-phospho β-catenin, and the positivity was grouped as negative, weak, moderate, and strong. DNA was isolated from frozen tissue or formalin-fixed materials, and the CTNNB1 mutation status was determined by direct sequencing. Of the 40 patients receiving COX-2 inhibitor treatment, there was one with complete remission, 12 with partial remission, 7 with stable disease, and 20 with progressive disease. The mutation sites in CTNNB1 were detected in 22 (55%) of the 40 cases: T41A (17 cases), S45F (3 cases), and T41I and S45P (1 each). The positive nuclear expression of non-phospho β-catenin showed a significant correlation with positive CTNNB1 mutation status detected by Sanger method (p = 0.025), and poor outcome in COX-2 inhibitor therapy (p = 0.022). In contrast, nuclear expression of β-catenin did not show a significant correlation with either CTNNB1 mutation status (p = 0.43) or outcome of COX-2 inhibitor therapy (p = 0.38). Nuclear expression of non-phospho β-catenin might more appropriately reflect the biological behavior of DF, and immunohistochemical staining with non-phospho β-catenin could serve as a more useful diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with DF.
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