Prognostic significance of BMP7 as an oncogene in hepatocellular carcinoma

This study aims to evaluate the association between BMP7 tissue expression and patient prognosis in hepatocellular carcinoma (HCC). The expression of BMP7 mRNA in HCC was characterized using real-time PCR and 30 pairs of fresh frozen HCC tissues and corresponding noncancerous tissues. BMP7 protein expression in HCC was confirmed using immunohistochemistry on a tissue microarray chip. Finally, BMP7 expression was correlated with conventional clinicopathological features of HCC and patient outcome. The expression of BMP7 mRNA and protein in HCC cells was much higher than in normal hepatic cells. Our results showed that the high expression of BMP7 in HCC was related to tumor size (p?<?0.001), histological differentiation (p?=?0.041), serum AFP (p?=?0.007), and tumor stage (p?<?0.001). Kaplan–Meier survival analysis showed that a high-expression level of BMP7 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that BMP7 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that a high-expression level of BMP7 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that BMP7 may be a potential target of antiangiogenic therapy for HCC.     

The RET oncogene in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto‐oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium. Cancer 2015;121:2137–2146. © 2015 American Cancer Society.     

Prognostic significance of USP10 as a tumor-associated marker in gastric carcinoma

Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, had been associated with growth of tumor cell. However, the role of USP10 in gastric cancer carcinogenesis had not been elucidated yet. The aim of this study was to investigate the expression level of USP10 in gastric carcinoma (GC) tissues and cell lines, then to evaluate the clinical significance of USP10 in GC patients. USP10, E-cadherin, Ki67 and p53 expressions were detected in 365 GC and 40 non-cancerous mucosa tissues by immunohistochemistry. Western blot for USP10 was performed on additional fresh GC tissues and GC cell lines. The expression level of USP10 in GC tissues was proved lower than that in non-cancerous mucosa tissues (p?<?0.05). It was also lower in GC cell lines (AGS, BGC-823 and MKN45 cells) than that in gastric epithelial immortalized cell line (GES-1). Clinicopathological analysis showed that USP10 expression was negatively correlated with gastric wall invasion (p?=?0.009), nodal metastasis (p?=?0.002), and TNM stage (p?=?0.000). In contrast, a positively correlation between the expression of USP10 and E-cadherin was found (p?<?0.05), but there was no relationship proved between Ki67, p53 and USP10 (p?>?0.05). On the Kaplan–Meier survival curves, we found poor prognosis in GC patients was associated with negative USP10 expression (p?<?0.05). Moreover, USP10 expression was an independent prognostic factor for the overall survival in multivariate analysis. Our findings suggested that USP10 was an independent predictor of prognosis of GC patients.     

Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma

BACKGROUND: Papillary thyroid carcinomas represent a diversity of morphologic subtypes and variants, but to the authors' knowledge the prognostic significance of subclassification is not clear. Therefore, the authors compared the value of histologic classification with a combined assessment of histologic key features such as marked nuclear atypia, tumor necrosis, and vascular invasion (i.e., histologic grade). METHODS: One hundred twenty-eight surgically treated patients with papillary carcinoma > 10 mm were studied. The tumors were subclassified and individual histologic features were examined and compared in univariate and multivariate survival analyses. RESULTS: Of all the cases, 55% were of the usual type, whereas 27% showed complex histologic features with different components present and 18% represented specific subtypes. Tall cell differentiation showed an increased frequency of tumor necrosis and vascular invasion, and tumors with solid areas had an increased occurrence of mitotic figures and vascular invasion. Patients with tall cell tumors tended to have reduced survival (P = 0.074), and two patients with columnar cell features died of the disease. When combined, the group of patients with all tumor subtypes had significantly reduced survival when compared with the remainder of patients (P = 0.034), although the difference was only minor. Histologic grade was highly significant (P = 0.0001) in survival analysis, together with mitotic frequency (P = 0.028), S-phase (P = 0.015), and G(2)M-phase fractions (P = 0.040). In multivariate analysis, tumor dimension (P = 0.019) and histologic grade (P = 0. 008) showed significant and independent prognostic importance, whereas subclassification was not found to be significant. CONCLUSIONS: Subclassification of papillary thyroid carcinomas had only a minor prognostic impact, whereas histologic grade was a strong and independent prognostic marker. The authors recommend that all papillary carcinomas be given a histologic grade based on a combined examination of nuclear atypia, tumor necrosis, and vascular invasion. [See editorial on pages 1766-68, this issue.] Copyright 2000 American Cancer Society.     

Prognostic factors in papillary carcinoma of the thyroid

In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hürthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men.     

Prognostic value of oncoprotein expressions in thyroid papillary carcinoma

The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC.     

Prognostic impact of EGF-receptor in papillary thyroid carcinoma.

In this study of papillary thyroid carcinomas, immunopositivity for EGF-receptor was present in a majority of the cases (96%), although different staining patterns were observed. A distinct membraneous reaction was found in 46%, whereas cytoplasmatic positivity of various degrees was present in 90% of the cases. Strong cytoplasmic EGF-receptor staining was significantly associated with extra-thyroidal growth of the primary tumour (P = 0.009), and it was furthermore related to decreased recurrence free survival (P = 0.006). Membraneous EGF-receptor staining was not associated with recurrence free survival or patient survival. Multivariate Cox analysis showed that lymph node metastases (P = 0.0009) and cytoplasmic EGF-receptor staining (P = 0.0048) was independent indicators of tumour recurrences in this group of surgically treated papillary thyroid carcinomas.     

Ret oncogene protein expression in papillary thyroid carcinoma and related lesions

BACKGROUND: Activation of Ret oncogenes, particularly Ret/PTC, has been identified in papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the immunostaining pattern of Ret oncogene protein in PTC and nodular non-PTC lesions with a fine chromatin pattern. MATERIALS AND METHODS: Ninety-three PTC and 139 nodular non-PTC lesions were microscopically reviewed to identify the nuclear changes of "limited nuclear features of PTC" (focal nuclear grooves, nuclear inclusions or optically clear nuclei) and areas of infiltrating carcinoma (IC) and were submitted for immunostaining with Ret oncogene protein antiserum. RESULTS: Immunoreactivity for Ret protein ranged from negative in follicular adenoma (FA) with a coarse chromatin pattern, to negative or weak reactivity in FA with a fine chromatin pattern, to strong reactivity in PTC with areas of infiltrating carcinoma (IC). In FA with fine chromatin, FA and follicular carcinoma (FC) containing an admixture of areas of coarse and fine chromatin, areas with nuclear changes with "limited nuclear features of PTC" displayed varying degrees of immunoreactivity. The intensity of immunostaining varied with the degree of nuclear change. The noninvasive component of PTC with IC usually showed more extensive and stronger reactivity than PTC without IC. PTCs with and without IC were associated with a rate of lymph node metastasis of 48% and 3%, respectively. CONCLUSIONS: The expression of Ret oncogenes (Ret/PTC, other unknown variants or wild type) is focally or extensively present in all PTC with IC. The degree of immunoreactivity is likely to be proportional to the potential for lymph node metastasis of PTC. In the context of this study and due to the specificity of Ret oncogenes, it is likely that nodular non-PTC lesions with a fine chromatin pattern and focal positive reactivity for Ret oncogene represent PTC-related lesions.     

甲状腺乳头状癌中CXCL12的表达及意义

目的：探讨趋化因子CXCL12在甲状腺乳头状癌组织中的表达及与临床病理特征的关系。方法：采用SP免疫组织化学法检测79例甲状腺乳头状癌、癌旁组织及33例良性甲状腺疾病组织标本中CXCL12的表达。结果：在癌旁甲状腺组织中,CXCL12表达阴性。在癌组织中,CXCL12高水平阳性表达于癌细胞胞浆,阳性表达率为69．6％。在良性甲状腺疾病中CXCL12阳性表达率为12．1％。癌组织与癌旁组织、良性甲状腺疾病组织中表达差异显著（P〈0．05）。CXCL12表达与甲状腺乳头状癌淋巴结转移呈正相关（P〈0．05）。结论：CXCL12可能在甲状腺乳头状癌淋巴结转移中起到一定作用。     

甲状腺乳头状癌BRAF基因突变及表达的临床意义研究

目的探讨BRAF基因点突变及B-raf蛋白表达在甲状腺乳头状癌发生中的临床意义。方法应用聚合酶链式反应(PCR)技术检测65例甲状腺病变石蜡组织中BRAF点突变,应用免疫组化方法检测112例甲状腺病变组织中B-raf蛋白的表达情况,并比较BRAF基因突变和B-raf蛋白表达的相关性。结果在46例甲状腺乳头状癌中有21例发生BRAF的点突变,突变率为45.7。BRAF基因突变位于第15外显子的1799位点,胸腺嘧啶突变为腺嘌呤(T1799A)。在结节性甲状腺肿和滤泡状癌中未检测到BRAF的突变。乳头状癌BRAF基因突变率与结节性甲状腺肿比较,差异具有统计学意义(P<0.05)。但是与患者的性别、年龄、组织学类型、淋巴结转移和肿瘤分期无相关性(P>0.05)。在乳头状癌、滤泡状癌和结节性甲状腺肿中B-raf蛋白表达阳性率分别为65.1、47.6和15.4。结果显示,乳头状癌B-raf蛋白阳性表达率与良性病变比较,差异具有统计学意义(P<0.05)。在乳头状癌中BRAF基因突变与B-raf蛋白表达水平呈正相关(P<0.05)。乳头状癌与滤泡状癌比较,B-raf蛋白表达水平两组间无统计学意义(P>0.05)。结论甲状腺乳头状癌BRAF基因突变率和蛋白表达水平的增高,提示BRAF基因在乳头状癌发病中可能发挥重要的作用。对甲状腺肿瘤的病理诊断也具有辅助价值。     

Expression and clinical significance of STIP1 in papillary thyroid carcinoma

The aim of this study was to detect stress-induced phosphoprotein 1 (STIP1) expression in papillary thyroid carcinoma (PTC) and to analyze its association with prognosis of PTC patients. Immunohistochemistry was performed to detect the expression of STIP1 in 113 PTC tissues and paired adjacent noncancerous tissues. The χ2 test was used to analyze the relationship between STIP1 expression and clinicopathological characteristics. Survival curves were plotted by the Kaplan–Meier method and compared using the log-rank test. Survival data was evaluated using univariate and multivariate Cox regression analysis. We identified abnormally elevated expression of STIP1 protein in PTC tissues compared to paired adjacent noncancerous tissues. Clinicopathological analysis showed that STIP1 expression was significantly correlated with tumor size (P?=?0.017), lymph node metastasis (P?=?0.007), and TNM stage (P?=?0.026). Patients with higher STIP1 expression had shorter overall survival time, whereas those with lower STIP1 expression had longer survival time. Multivariate analysis suggested that STIP1 expression might be an independent prognostic indicator (P?<?0.05) for the survival of patients with PTC. In conclusion, our findings provide evidences that positive expression of STIP1 in PTC may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with PTC.     

明胶酶A在甲状腺乳头状癌中的表达及临床意义

目的 :探讨明胶酶A在甲状腺乳头状癌中的表达及其与甲状腺乳头状癌侵袭与转移的关系 ,方法 :用原位杂交、免疫组化SP法检测95例甲状腺乳头状癌及 5 9例癌旁组织中明胶酶AmRNA、蛋白的表达水平。结果 :明胶酶AmRNA和蛋白在甲状腺乳头状癌中的阳性率分别为 74 7% ( 71/95 )、77 9% ( 74/95 ) ,而在癌旁组织中的阳性率分别为 10 2 % ( 6/5 9)、2 5 4% ( 15 /5 9) ,两者差异有统计学意义 ,P <0 0 1。明胶酶AmRNA及其蛋白在甲状腺乳头状癌 (微小癌、腺内型、腺外型 )的阳性率分别为5 9 3 % ( 16/2 7)、 80 0 % ( 4 0 /5 0 )、 83 3 %( 15 /18) ;66 7% ( 18/2 7)、 80 0 % ( 4 0 /5 0 )、88 9% ( 16/18) ,癌组织各型间差异无统计学意义 ,P >0 0 5。淋巴结有癌转移组的阳性率分别为 91 4% ( 3 2 /3 5 )、97 1% ( 3 4/3 5 ) ,淋巴结无癌转移组的阳性率分别为 65 0 % ( 3 9/60 )、66 7%( 4 0 /60 ) ,两者差异有统计学意义 ,P <0 0 1。结论 :明胶酶A在甲状腺乳头状癌中呈高表达 ,与甲状腺乳头状癌侵袭与转移有密切关系     

E-cadherin在甲状腺乳头状腺癌中的表达及临床意义

目的：研究Ｅ－ｃａｄｈｅｒｉｎ在甲状腺乳头状腺癌中的表达,并探讨其能否成为甲状腺乳头状腺癌独立的预后因素。方法：应用免疫组化方法,对４０例甲状腺乳头状腺癌、１０例甲状腺滤泡型腺瘤和１０例甲状腺正常组织进行了Ｅ－ｃａｄｈｅｒｉｎ表达的研究,并对可能影响甲状腺癌病人预后的有关因素进行了时序检验单因素生存分析。结果：９例（２２．５％）甲状腺乳头状腺癌Ｅ－ｃａｄｈｅｒｉｎ表达阳性,余多数呈不表达或弱阳性表     

甲状腺乳头状癌中ATAD2的表达及其临床意义

目的:探讨甲状腺乳头状癌中三磷酸腺苷酶家族蛋白2（ATAD2）的表达及其临床意义。方法:采用免疫组织化学染色法检测95例甲状腺乳头状癌患者以及50例甲状腺良性病变患者（30例甲状腺腺瘤,20例结节性甲状腺肿）中ATAD2的表达水平,分析ATAD2与患者临床病理特征之间的关系。结果:甲状腺乳头状癌中ATAD2的表达明显高于甲状腺良性病变组织,二者差异有统计学意义（P<0.05）。甲状腺乳头状癌中ATAD2表达与甲状腺乳头状癌患者的淋巴结转移、远处转移以及TNM分期明显相关（P<0.05）,与患者年龄、性别、肿瘤大小、肿瘤多灶性无关（P>0.05）。结论:ATAD2蛋白在甲状腺乳头状癌中表达上调,可能在甲状腺乳头状癌发生发展中发挥重要作用,检测ATAD2有助于判断甲状腺癌浸润转移潜能。     

Twist1在乳头状甲状腺癌中的表达及意义

目的:检测Twist1在乳头状甲状腺癌组织及细胞中的表达情况,并探讨其与乳头状甲状腺癌的临床病理因素和生物学行为的关系.方法:研究应用免疫组织化学方法检测120例乳头状甲状腺癌组织中Twist1的表达.体外细胞研究构建靶向Twist1的shRNA真核表达质粒,转染乳头状甲状腺癌细胞,采用MTT法检测细胞转染前后增殖能力变化,通过Boyden小室实验以穿过人工基底膜的细胞数量评估甲状腺癌细胞株体外侵袭能力的变化;同时检测细胞间连接及黏附相关蛋白E-cadherin、Vimentin等的表达情况.结果:免疫组化结果显示,Twist1在乳头状甲状腺癌中的表达水平与肿瘤的淋巴结转移呈正相关(P＜0.05),与其他临床病理因素(如临床分期、分化程度等)没有明显相关性.RNA干扰使乳头状甲状腺癌细胞株IHH-4中Twist1的表达下调;与阴性对照组比较,Twist1蛋白表达分别降低了50％(KD-A)、60％(KD-B)和64％(KD-C).且E-cadherin表达上调,Vimentin表达下调.结论:Twist1在人乳头状甲状腺癌中表达上调,与肿瘤的淋巴结转移相关.针对Twist1的shRNA真核表达载体能明显抑制乳头状甲状腺癌细胞的Twist1表达,并有效抑制乳头状甲状腺癌细胞的体外侵袭能力.Twist1可能通过调控乳头状甲状腺癌的上皮-间质转化过程来影响其局部浸润及淋巴结转移.     

Diagnostic significance of elevated expression of HBME-1 in papillary thyroid carcinoma

Tumor Biology - This study examined the association between hector battifora mesothelial antigen-1 (HBME-1) expression and papillary thyroid carcinoma (PTC). A total of 206 patients were enrolled...     

甲状腺乳头状癌组织中TRIM14的表达及临床意义

目的:探讨三结构域蛋白14（tripartite motif containing 14,TRIM14）在甲状腺良性结节和甲状腺乳头状癌（papillary thyroid carcinoma,PTC)组织中的表达差异,并分析TRIM14表达水平与甲状腺乳头状癌患者各临床病理特征间的关系。方法:收集我院92例手术切除且病理证实为PTC患者的临床病理资料及组织标本以及50例甲状腺良性结节组织标本。用免疫组织化学检测入组标本中TRIM14表达水平,并分析TRIM14表达与患者临床病理特征间的关系。结果:PTC组织中TRIM14表达阳性率为88.04%,甲状腺良性结节中TRIM14表达阳性率为40%,两者差异有统计学意义（P＜0.001）;TRIM14表达与PTC患者T分期及肿瘤危险度分层相关（P＜0.05）。结论:TRIM14高表达于PTC组织中,有望成为新的PTC肿瘤标志物。TRIM14的表达与PTC患者T分期及危险度分层相关,提示TRIM14可能影响PTC发生发展。     

肿瘤相关巨噬细胞在甲状腺乳头状癌中的分布及临床意义的初探

  目的  初步探讨肿瘤相关巨噬细胞（tumor-associated macrophages, TAMs）及M2型TAMs与甲状腺乳头状癌（papillary thyroid carcinoma,PTC）临床病理特征的关系。  方法  选取2010年1月至2017年12月云南省肿瘤医院 昆明医科大学第三附属医院就诊的68例患者的临床资料,其中甲状腺癌51例（PTC 42例,甲状腺鳞状细胞癌9例）,甲状腺良性病变17例。免疫组织化学法检测术后病理组织中TAMs和M2型TAMs的分布情况,并分析其与患者临床病理特征的关系。  结果  甲状腺癌组织中CD68+TAMs、CD206+TAMs和CD68+/CD206+TAMs的分布强度均高于甲状腺良性病变（P<0.05）。在PTC组织内存在CD68?/CD206+TAMs形式的分布。42例PTC中,有淋巴结转移组及肿瘤大小≥2 cm组中CD68+TAMs和CD68+/CD206+TAMs的分布强度高于无淋巴结转移组和肿瘤大小<2 cm组（P<0.05）。在PTC大小<2 cm及Ⅰ期或Ⅱ期的情况下,CD206+TAMs分布强度高于CD68+TAMs（均P<0.001）。PTC组织中CD206+TAMs分布强度与CD68+TAMs分布强度呈正相关（P<0.05）。在PTC患者的T3、TgAb、FT3及FT4正常组与异常组之间CD68+TAMs的分布差异具有统计学意义（P<0.05）;CD68+/CD206+TAMs的分布分别在PTC患者的T3、FT3及FT4正常组与异常组之间差异具有统计学意义（P<0.05）。  结论  TAMs、M2型TAMs对PTC的发生具有一定促进作用,TAMs促进PTC颈部淋巴结转移、肿瘤的生长及影响甲状腺激素水平的调节;在PTC微环境中未发现M2型TAMs从属于TAMs的关系,而在PTC早期微环境中主要是以M2型TAMs为主。      

Ku80在甲状腺乳头状癌组织中的表达及其临床意义

目的:探讨甲状腺乳头状癌组织中Ku80的表达水平及其与临床病理特征的关系。方法:收集22例甲状腺乳头状癌患者的组织蜡块,应用免疫组化检测甲状腺乳头状癌、癌旁组织中Ku80的表达,并分析Ku80表达与甲状腺乳头状癌临床病理特征的关系。结果:甲状腺乳头状癌组织中Ku80阳性表达率为63.6%,癌旁组织阳性表达率为22.7%,差异有统计学意义（P<0.05）;Ku80表达与患者的肿瘤TNM分期中T分期有关（P=0.005）,与患者年龄、性别、是否有淋巴结转移、肿瘤大小、发病部位及是否有其他合并症无显著相关性（P>0.05）。结论:Ku80在甲状腺乳头状癌中高表达,并与肿瘤T分期显著相关。     

甲状腺乳头状癌与乳头状增生的病理研究

  目的 探讨Galectin3，CK19及Ki-67在甲状腺乳头状癌与乳头状增生中的表达，寻找有助于两者鉴别诊断的标志物。方法 运用免疫组化方法检测100例甲状腺乳头状癌、100例良性乳头状增生中Galectin3，CK19及Ki-67的表达。结果 Galectin3，CK19及Ki-67在甲状腺乳头状癌阳性表达率分别为100 %，97 %及93 %，而在乳头状增生中表达率分别为13 %，30 %及1 %，3种蛋白在乳头状癌与良性乳头状增生间差异有统计学意义（P＜0.05）。在乳头状癌中2种或3种蛋白同时阳性表达为94.3 %，而乳头状增生为0。结论 Galectin3，CK19及Ki-67是鉴别诊断甲状腺乳头状癌与乳头状增生的有用标志物，尤其联合使用更有价值。