P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.     

C-MYC基因在肝癌与肝硬化组织中扩增的实验研究

目的 研究C-MYC基因在肝癌及肝硬化组织中的扩增情况。方法 采用聚合酶链式反应(PCR)对32例肝癌及12例肝硬化组织中的C-MYC基因扩增情况进行研究，并通过激光密度扫描仪对琼脂糖凝胶EB染色底片进行积分光密度分析。结果 正常组织无C-MYC扩增，C-MYC与N-MYC L-MYC比值95％可信区间为0．1325-0．5632，肝硬化组织扩增阳性率为8．33％，肝癌组织扩增阳性率43．75％。结论 肝癌组织C-MYC扩增率高于正常组织和肝硬化组织，且C-MYC扩增者大多有淋巴结转移，组织分化差。检测C-MYC基因扩增情况可对肿瘤发生、发展及预后进行判断，并指导临床基因治疗。     

Blastic mantle cell lymphoma associated with Burkitt-type translocation and hypodiploidy

Two elderly men with stage IV mantle cell lymphoma (MCL) rapidly developed a leukaemic phase with unusually high blast counts that proved fatal. One lymph node biopsy showed diffuse MCL, the other blastic morphology. In addition to t(11;14), there were t(8;14) and t(1;19) in case 1 and dup(8)(q24q13) in case 2. Fluorescence in situ hybridization revealed genomic fusion of IgH/MYC genes in case 1 and an extra copy of C-MYC gene in case 2. The genomic alteration of C-MYC oncogene is probably implicated in the blastic transformation and aggressive behaviour of the disease.     

Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

INTRODUCTION Gastric cancer is the third most frequent type of cancer in the world[1]. In Northern Brazil, the State of Pará presents a high incidence of this neoplasia type and its capital, Belém, is ranked eleventh in number of gastric cancers per inh…     

Diagnosis of Burkitt lymphoma in due time: a practical approach

The quick diagnosis of Burkitt lymphoma (BL) and its clear-cut differentiation from diffuse large B-cell lymphoma (DLBCL) is of great clinical importance because treatment strategies for these two disease entities differ markedly. As these two lymphomas are difficult to distinguish using the current World Health Organization classification, we studied 39 cases of highly proliferative peripheral blastic B-cell lymphoma (HPBCL) to establish a practical differential-diagnostic algorithm. Characteristics set for BL were a typical morphology, a mature B-cell phenotype of CD10+, Bcl-6+ and Bcl-2- tumour cells, a proliferation rate of >95%, and the presence of C-MYC rearrangements in the absence of t(14;18)(q32;q21). Altogether, these characteristics were found in only five of 39 cases, whereas the majority of tumours revealed mosaic features. We then followed a pragmatic stepwise approach for a classification algorithm that included the assessment of C-MYC status to stratify HPBCL into four predefined diagnostic categories (DC), namely DC I (5/39, 12.8%): 'classical BL', DC II (11/39, 28.2%): 'atypical BL', DC III (9/39, 23.1%): 'C-MYC+ DLBCL' and DC IV (14/39, 35.9%): 'C-MYC- HPBCL'. This proposal may serve as a robust and objective operational basis for therapeutic decisions for HPBCL within 1 week and is applicable to be evaluated for its prognostic relevance in clinical trials with uniformly treated patients.     

恶性淋巴瘤诊断中荧光原位杂交分析基因状态的研究

目的 探讨恶性淋巴瘤中基因重排的特点.方法 回顾性分析87例恶性淋巴瘤组织样本,利用荧光原位杂交技术,分别检测弥漫大B细胞淋巴瘤、滤泡性淋巴瘤、黏膜相关淋巴组织淋巴瘤、套细胞淋巴瘤、Burkitt淋巴瘤和间变性大细胞淋巴瘤中BCL-6、BCL-2、MALT1、CCND1、C-MYC和ALK基因重排.结果 弥漫大B细胞性淋巴瘤中BCL-6基因重排的阳性率为29.03％(9/31),滤泡性淋巴瘤中BCL-2基因重排的阳性率为61.11％(11/18),黏膜相关淋巴组织淋巴瘤中MALT1基因重排的阳性率为47.37％(9/19),套细胞淋巴瘤中CCND1基因重排的阳性率为88.88％(8/9),Burkitt淋巴瘤中C-MYC基因重排的阳性率为100％(2/2)和间变性大细胞淋巴瘤中ALK基因重排的阳性率为75.00％(6/8).结论 基因重排对恶性淋巴瘤的诊断具有重要的实际价值.     

诱导多能干细胞建系过程中关键转录因子的作用

通过添加OCT4、SOX2等转录因子,体外诱导细胞重编程获得诱导多能干细胞是近年干细胞领域的一大突破.OCT4、SOX2和NANOG等转录因子在启动细胞重编程、维持诱导多能干细胞多能性和决定其是否走向分化方面起了关键作用.对这些转录因子作用机制的了解,有助于细胞莺编程分子机制的进一步阐明.     

基底细胞样乳腺癌老年患者Ki-67表达与TopoⅡα、C-MYC基因的相关性

目的探讨基底细胞样乳腺癌(BLBC)和非BLBC(NBLBC)癌组织中TopoⅡα、C-MYC基因扩增与Ki-67表达的关系。方法该院临床病理诊断中心经石蜡包埋的乳腺癌组织,其中100例BLBC癌组织、100例NBLBC癌组织,对照组选取100例同期周围正常乳腺组织。结果TopoⅡα与C-MYC基因改变类型主要为扩增与缺失,TopoⅡα、C-MYC和Ki-67在对照组表达不显著。100例BLBC病理组织中,TopoⅡα与C-MYC基因扩增分别为43例和51例,缺失分别为57例49例;Ki-67阳性76例,阴性24例;TopoⅡα、C-MYC基因扩增与Ki-67表达在Spearman等级相关分析中有统计学意义(P0.05)。100例NBLBC病理组织中,TopoⅡα与C-MYC基因扩增分别为34例和43例,缺失66例和57例;Ki-67阴性16例,阳性84例;Spearman等级相关分析,TopoⅡα、C-MYC基因扩增与Ki-67表达相关(P0.05),TopoⅡα与C-MYC基因扩增呈正相关(P0.05)。与NBLBC比较,BLBC的TopoⅡα与C-MYC基因扩增略多。结论 TopoⅡα、C-MYC基因扩增与Ki-67相关。与NBLBC比较,BLBC癌组织的TopoⅡα、C-MYC基因扩增较多,TopoⅡα与C-MYC基因扩增可能参与乳腺癌的发生发展过程。