子宫颈病变中DEK和Ki-67蛋白过表达及其意义

目的研究DEK和Ki-67基因蛋白检测对宫颈病变的临床病理学意义。方法20例正常宫颈上皮、83例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)、87例宫颈鳞状上皮癌(squamous cell carcinoma,SCC)和32例宫颈腺癌(adenocarci-noma)共222例存档蜡块选自延边大学医院、延边妇幼保健院和延边肿瘤医院病理科。应用组织芯片和免疫组化方法检测DEK和Ki-67蛋白在上述病变组织中的表达。结果20例非肿瘤性的正常宫颈上皮组织标本中DEK和Ki-67蛋白表达阴性,而DEK蛋白和Ki-67蛋白的阳性表达率在SCC中分别为82.8%(72/87)和88.5%(77/87),在子宫颈腺癌标本中分别为84.4%(27/32)和93.8%(30/32),而在CIN-1标本中分别为54.3%(19/35)和57.1%(20/35),在CIN-2标本中分别为69.2%(18/26)和76.9%(20/26),在CIN-3标本中分别为77.3%(17/22)和81.8%(18/22)。DEK和Ki-67蛋白均与宫颈癌分级和分期不相关。结论DEK蛋白检测可以作为宫颈癌细胞的增殖指标之一,与Ki-67蛋白有着相似的阳性表达部位和表达率,可作为宫颈癌的早期诊断指标,并有望成为宫颈癌靶向治疗的新靶点。     

The kinetics of relapse in DEK‐NUP214‐positive acute myeloid leukemia patients

Preemptive treatment of relapse of acute myeloid leukemia (AML) holds the promise to improve the prognosis of this currently highly lethal condition. Proposed treatment modalities applicable in preemptive cytoreduction (e.g., demethylating agents or standard chemotherapy) differ substantially in interval from administration to antileukemic effect. The t(6;9) balanced translocation, producing the DEK‐NUP214 fusion protein, is seen in only 1% of patients with AML. We hypothesized that in these patients, who relapse with a very high frequency, a more detailed knowledge of leukemic relapse growth kinetics would improve the personalized decision‐making regarding re‐administration of chemotherapy. Based on standardized quantitative PCR data, we therefore delineated the relapse kinetics in a cohort of 27 relapsing DEK‐NUP214‐positive patients treated in four different European countries. The prerelapse leukemic burden increased with a median doubling time of 13 d (range: 5–51 d, median: 0.71 logs/month, range: 0.18–1.91 logs/month), with FLT3‐ITD‐positive patients relapsing significantly faster than FLT3‐ITD‐negative ones (median: 0.9 vs. 0.6 logs/month, Wilcoxon rank sum test, P = 0.041). Peripheral blood and bone marrow were equally useful for minimal residual disease (MRD) detection, and thus, we found that with sampling intervals of 2 months, 94% of relapses would be detected with a median time from MRD detection to hematological relapse of 64 d. In conclusion, this data provide algorithms for handling the rare patients with DEK‐NUP214‐positive AML allowing for planning of both MRD follow‐up and, upon molecular relapse, the timing of cytoreduction or possibly transplant procedures.     

DEK overexpression is correlated with the clinical features of breast cancer

To investigate the clinicopathological significance of DEK overexpression in breast cancers, a total of 196 cases, including 20 of normal tissues, 12 of intraductal hyperplasia, 31 of ductal carcinoma in situ (DCIS) and 133 of invasive ductal carcinoma of the breast, were selected from the Department of Pathology, Yanbian Tumor Hospital for immunohistochemical staining of DEK, estrogen (ER), progesterone (PR) and Ki-67 proteins. In results, DEK protein had higher positivity in DCIS, compared with the adjacent normal breast tissues. Also, DEK protein was strongly positive in invasive ductal carcinoma of the breast on immunohistochemistry, which was significantly higher than normal breast tissues. However, only two (2/12) cases of intraductal hyperplasia of the breast showed positive staining for DEK protein. Additionally, DEK overexpression was significantly correlated with the increased proliferating index of Ki-67. For the histological grade, DEK positive rate was only 39.6% in G1 breast cancers, but significantly higher in G2 (92.3%) and G3 (97.0%) cases (P<0.05). Also, a strongly positive rate of DEK was lower in Stage-0 (21.4%) and Stage-I (40.9%) compared with Stage-IIa (87.5%), Stage-IIb (89.7%) and Stage-IIIa (92.3%) (P<0.05). And DEK protein showed higher expression level in < 3 years disease free survival breast cancers than it did in ≥ 3 years disease free survival cases (P<0.05). However, no statistically difference was found among DEK expression, lymph node metastasis, and ER and PR expressions. In conclusion, DEK overexpression appears to be associated with breast cancer progression and DEK may potentially be used as a breast cancer biomarker for the early diagnosis, prognostic evaluation and therapeutic target for breast cancer.     

肝细胞癌中DEK蛋白的表达及其意义

目的 探讨DEK蛋白在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及意义.方法 应用组织芯片技术进行免疫组化染色检测92例HCC和58例癌旁肝组织标本中DEK的表达,结合临床相关因素进行统计分析.结果 组织芯片检测结果中实际有效146个,其中HCC组织88例,癌旁肝组织58例.HCC、癌旁肝组织中DEK阳性表达率分别为39.8%、5.2%,HCC组织中DEK阳性表达率明显高于癌旁肝组织(P=0.000);HCC组织中DEK阳性表达与组织分化程度、是否转移密切相关(P<0.05).结论 HCC组织中DEK蛋白的表达对其诊断及预后有一定参考价值.     

The putative oncoprotein DEK, part of a chimera protein associated with acute myeloid leukaemia, is an autoantigen in juvenile rheumatoid arthritis.

The 45-kD autoantigen associated with juvenile rheumatoid arthritis (JRA) has been isolated from HeLa cell nuclei and purified about 2500-fold to near homogeneity in a five-step chromatographic procedure. Purification of the antigen was monitored by immunoblot assays using a nearly monospecific anti-45-kD serum from a child with JRA. Tryptic peptide mapping and partial amino acid sequencing of the purified 45-kD antigen demonstrated its identity with the DEK protein. DEK is a 43-kD protein of unknown function expressed by the putative oncogene dek located on chromosome 6. As a result of a (6;9) translocation offociated with a rare subtype of acute myeloid leukaemia a chimeric protein containing most of DEK amino acids at the N-terminus is found in leukaemic cells (von Linden et al., Mol Cell Biol. 1992; 12: 1687-97). The 43-kD DEK was detected by immunoblotting with serum from a patient with JRA in a variety of rat tissues, and was most abundant in the spleen and in bone marrow.