AJSP最新研究报告: TP53荧光原位杂交对诊断儿童成骨肉瘤具有100%的特异性 ...

Am J Surg Pathol. 2018 Mar 14. doi:10.1097/PAS.0000000000001054. [Epub ahead of print]

Fluorescent In Situ Hybridization forTP53 in the Diagnosis of Pediatric Osteogenic Sarcoma.

TP53荧光原位杂交在诊断儿童成骨肉瘤中的作用。

Marrano P, Shago M, Somers GR,Thorner PS.

Abstract

Osteogenic sarcoma (OS) is the mostcommon malignant bone tumor in children and adolescents. Despite advances inmolecular genetic characterization of pediatric and adult tumors, the diagnosisof OS still depends almost entirely on light microscopy.

成骨肉瘤（OS）是儿童和青少年中最常见的恶性骨肿瘤。尽管有多种儿童和成人肿瘤的分子遗传学特征获得了进展，但OS的诊断几乎完全依赖于光学显微镜。

The lack of consistent genetic changesin OS has greatly hindered the development of any diagnostic molecular test.

OS缺乏一致的遗传变化极大地阻碍了其诊断分子检测的发展。

Recently, whole-genome sequencing hasshown that ~50% of cases of OS have a translocation involving the TP53 genewith breakpoints confined to the first intron.

最近，全基因组测序显示大约50％的OS病例存在TP53基因的易位，断裂点仅限于第一个内含子。(In all, 95% of OS have either sequence mutations or structural variations in the TP53 gene and up to 53% of cases have single nucleotide variations and/or structural variations in the RB1, ATRX, and DLG2 genes by wholegenome sequencing（95％的OS具有TP53基因中的序列突变或结构变异，高达53％的病例呈现为单核苷酸突变和/或RB1，ATRX和DLG2基因的结构变异）.-Cell Rep. 2014;7:104–112. )

We developed a 2 color break-apartfluorescent in situ hybridization (FISH) probe for intron 1 of TP53 and appliedit to an archived series to assess its diagnostic utility.

作者为TP53的内含子1开发了一种双色荧光原位杂交（FISH）探针，并以存档病例进行检测以评估其诊断效用。

The study group included 37 cases of OS(including osteoblastic, chondroblastic, and fibroblastic), as well as 53 casesof non-OS pediatric sarcomas (including Ewing sarcoma, rhabdomyosarcoma,undifferentiated small cell sarcoma, CCNB3-BCOR sarcoma, CIC-DUX sarcoma,synovial sarcoma, and malignant peripheral nerve sheath tumor) and 27 cases ofbenign bone lesions (including osteoblastoma, chondromyxoid fibroma, fibrousdysplasia, and fibro-osseous dysplasia). 

研究组包括37例OS（包括成骨细胞型，成软骨细胞型和成纤维细胞型），以及53例非OS儿童肉瘤（包括尤文肉瘤，横纹肌肉瘤，未分化小细胞肉瘤，CCNB3-BCOR肉瘤，CIC-DUX肉瘤，滑膜肉瘤和恶性外周神经鞘瘤）和27例良性骨病变（包括成骨细胞瘤，软骨粘液纤维瘤，纤维结构不良和纤维骨性发育不良）。

A rearranged signal was found in 20/37cases (54%) of OS and in none of the other sarcomas or benign bone lesions,giving the FISH test 100% specificity for a diagnosis of OS.

在20/37例（54％）OS中证实了重排信号的存在，在其他肉瘤或良性骨病变中没有发现重排信号，FISH检测对OS的诊断具有100％的特异性。

p53 immunostaining was generally notpredictive of the results obtained by FISH and could not substitute for thistest.

p53免疫染色通常不能预测FISH获得的结果，不能用于代替FISH测试。

This FISH probe offers a simple andspecific genetic test to aid in the diagnosis of OS, despite the geneticcomplexity of this tumor.

尽管OS具有遗传复杂性，但该FISH探针提供了简单且特异性的基因检测方法，用以帮助诊断OS。

PMID:29543677