Microvessel density, cyclo-oxygenase 2 expression, K-ras mutation and p53 overexpression in colonic cancer

BACKGROUND: Tumour angiogenesis, cyclo-oxygenase (COX) 2 expression, K-ras mutation and p53 overexpression are commonly involved in colorectal tumorigenesis, but their interrelationship and clinicopathological effects remain inconclusive. METHODS: Clinicopathological data from 114 consecutive patients with primary stage III colorectal cancer were evaluated prospectively. Microvessel density (MVD) of the tumour was defined by counting the number of microvessels in hotspots, visualized by immunocytochemical staining of endothelial CD34. K-ras mutation was analysed by the restriction enzyme cleavage method. COX-2 expression and p53 overexpression were determined by immunocytochemistry. RESULTS: Increased MVD in hotspots was significantly associated with COX-2 expression (P < 0.001), K-ras mutation (P = 0.007) and p53 overexpression (P = 0.006). COX-2 expression was not associated with either K-ras mutation or p53 overexpression. Clinicopathologically, greater MVD and COX-2 expression were significantly associated with vascular invasion of cancer cells (MVD, P = 0.027 and COX-2 expression, P = 0.006), but p53 overexpression and K-ras mutation were not. Multivariate analysis indicated that greater MVD (P = 0.002) and p53 overexpression (P = 0.016) were significant independent predictors of tumour recurrence, whereas COX-2 expression (P = 0.634) and K-ras mutation (P = 0.356) were not. CONCLUSION: Tumour angiogenesis may be associated with tumour metastasis and is significantly influenced by K-ras mutation, p53 overexpression and COX-2 expression in patients with colonic cancer.     

前列腺癌TSP-1的表达与血管新生的关系及意义

目的：探讨良性前列腺增生及前列腺癌中血管生成与血小板反应素-1（TSP-1）表达的相关性。方法：应用免疫组织化学方法检测32例良性前列腺增生和32例前列腺癌组织中TSP-1的表达及微血管密度（MVD）。结果：前列腺癌组织中TSP-1表达显著低于良性前列腺增生（P〈0．05）,MVD则明显升高（P〈0．05）;随着肿瘤分期的进展,浸润转移性癌中TSP-1的表达降低甚至缺失,而MVD却逐渐升高。结论：TSP-1在前列腺癌中呈低表达,与前列腺癌的血管新生相关;作为一种内源性血管新生抑制剂,它具有抑制肿瘤生长及血管新生的作用。     

Cytoplasmic induction and over-expression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment

OBJECTIVE: To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). RESULTS: For both BPH and prostate cancer, COX-1 expression was primarily in the fibromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was significantly greater (P = 0.008), with a change in the staining pattern from membranous to cytoplasmic (P < 0.001). COX-2 expression was significantly higher in poorly differentiated than in well differentiated tumours (P < 0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH. CONCLUSION: This is the first study to assess the co-expression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and significantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.     

Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence

OBJECTIVE: To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization. PATIENTS AND METHODS: We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field. RESULTS: Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months). CONCLUSION: These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer.     

The relation of p53 protein nuclear accumulation and angiogenesis in human prostatic carcinoma

All neoplasms require angiogenesis and resulting neovascularity for growth beyond 1 mm(2). Quantitative microvessel density (MVD) has been shown to provide staging and prognostic significance in human prostate cancer (CaP). recently, it has been demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. There is also an increased expression of vascular endothelial growth factor which promotes neovascularization. p53 gene mutation and MVD were investigated in men with prostate cancer. Sections from 103 radical prostatectomy cases were evaluated with immunohistochemistry to detect mutant p53 proteins. Quantitative MVD was performed on the cases exhibiting p53 positive staining and compared with negative fields of similar Gleason grade on the same histologic sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 20 cases, the MVD in p53 positive areas was greater than corresponding control regions (overall P<0.0001). Extent of p53 abnormality, as well as MVD, correlated with pathologic stage. These data suggest that mutations of the p53 tumour suppressor gene may be associated with increased angiogenesis in CaP. In addition to providing staging and prognostic information, this relationship potentially has therapeutic implications.     

塞来昔布联合奥沙利铂对人结肠癌裸鼠移植瘤生长的抑制作用

目的 观察塞来昔布或联合奥沙利铂对人结肠癌裸鼠移植瘤生长的影响并探讨其机制.方法 用人结肠癌HT-29细胞建立移植瘤模型,将裸鼠随机分为对照组、奥沙利铂组、塞来昔布组、联合用药组.给予相应药物35 d后,取移植瘤组织检测COX-2,VEGF mRNA和微血管密度.结果 塞来昔布组、奥沙利铂组和联合用药组抑瘤率分别为34.94%、30.53%和62.87%.奥沙利铂组COX-2,VEGF表达显著高于对照组(分别P＜0.05).奥沙利铂组微血管密度与对照组比较差异无统计学意义(P＞0.05).塞来昔布组和联合用药组COX-2,VEGF和MVD与对照组比较均显著下降(分别P＜0.05).结论 塞来昔布可抑制人结肠癌裸鼠移植瘤的生长和肿瘤血管生成.塞来昔布增加了奥沙利铂的抗肿瘤效果.     

环氧化酶-2在胃癌组织中的表达及其与血管生成的关系

目的探讨环氧化酶-2(COX-2)在胃癌组织中的表达及其与肿瘤血管生成的关系。方法应用免疫组织化学(免疫组化)法检测96例胃癌手术切除标本中COX-2的表达,采用抗CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)。分析COX-2表达与MVD和胃癌主要临床病理特征的相关性。结果胃癌组织COX-2阳性表达率和MVD分别为80.2%和32.5±8.3,显著高于正常胃黏膜的13.3%和13.1±2.4;P<0.01。临床TNM分期中Ⅲ、Ⅳ期胃癌标本COX-2表达率与MVD为91.4%和34.9±8.7,显著高于Ⅰ和Ⅱ期胃癌标本(P<0.01)。伴有淋巴结转移的胃癌组织中COX-2表达率和MVD分别为87.9%和35.0±8.5,与无淋巴结转移病例相比,差异有统计学意义(P<0.05)。Spearman等级相关分析表明,COX-2表达与MVD呈显著正相关(γ=0.311,P<0.01)。结论COX-2表达在胃癌的肿瘤血管生成中起重要作用,COX-2及其诱导的血管生成与胃癌的浸润和转移密切相关。     

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

OBJECTIVES: To determine whether COX-2, bcl-2 and neoangiogenesis are related to human prostate cancer relapse after definitive surgical treatment and progression toward androgen independence and to evaluate the association between the patterns of these tumoral biomarkers and other standard clinico-pathological parameters (such as Gleason score, PSA, TNM stage). MATERIALS AND METHODS: We retrospectively analyzed the records on 126 prostate cancer samples from patients treated at our University Hospital from 1995 to 2002. The 72 patients with clinically localized disease (group 1) had undergone radical prostatectomy. Another 54 patients (group 2) had metastatic androgen-independent disease. Archived material relating to the subjects was then immunostained for bcl-2, COX-2 and CD-31, using an anti-bcl-2 monoclonal primary antibody, an anti-COX-2 polyclonal rabbit antibody and an anti-CD-31 monoclonal mouse antibody to evaluate neoangiogenesis (MVD, microvessel density). RESULTS: We found that bcl-2, COX-2 and MVD expression increased from group 1 to group 2. The intergroup difference was significant only for high MVD (P < 0.05). On the other hand, high MVD, high bcl-2 and high COX-2 expression was correlated with a higher PSA level (P < 0.01), whereas only a high MVD was also related with Gleason score (P < 0.05). We used univariate analysis to evaluate the prognostic impact of biologic and clinico-pathologic parameters on the disease-free-survival of 72 patients treated by radical prostatectomy. A total of 30 patients (41.6%) experienced biochemical relapse; bcl-2, COX-2 and MVD significantly correlated with disease relapse in these patients. In fact, we observed disease relapse in 24/45 (53%) with high bcl-2 expression, in 15/21 (71%) with a high MVD count and finally, in 30/58 (52%) with high COX-2 expression. Finally, PSA value and Gleason score were the only two biologic markers significantly associated to disease relapse in a multivariate analysis. CONCLUSIONS: Our results strongly support a role for bcl-2, COX-2 and angiogenesis in the development and progression of prostate cancer. Of course, we are aware of the small sample size considered in our study. Further investigations would better clarify the prognostic and therapeutic implications of these findings.     

Transrectal colour Doppler ultrasonography for quantifying angiogenesis in prostate cancer

OBJECTIVE: To assess the correlation between angiogenesis and Doppler signal intensity using transrectal colour Doppler ultrasonography (CDUS) in patients with prostate cancer. PATIENTS AND METHODS: The study comprised 56 patients who underwent radical prostatectomy and had untreated tumours with a volume of> 0.1 mL in the peripheral zone. CDUS images were recorded on videotape before surgery. The Doppler signal intensity in tumours was evaluated using the colour pixel intensity (PI). Microvessel density (MVD) and vascular endothelial growth factor (VEGF) immunoreactivity were determined in the prostatectomy specimens. Microvessels were identified by immunohistochemical staining of endothelial cells for CD31. RESULTS: The PI in the tumour correlated with MVD (P < 0.001) and increased with higher levels of VEGF immunoreactivity (P = 0.004). There was no correlation between Gleason score and MVD or PI in the tumour. CONCLUSION: Blood flow assessed by CDUS may reflect the state of angiogenesis in prostate cancer. CDUS may be a useful technique for predicting tumour progression or prognosis, and may be useful for monitoring the effects of anti-angiogenic agents in the future.     

Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium

BACKGROUND: Chronic inflammation has been suggested to be linked to the development and progression of prostate cancer. An inflammatory microenvironment may support the development of malignancy by upregulation of proinflammatory cytokines and cyclooxygenase-2 (COX-2). Recent studies have suggested that COX-2 is upregulated in cancer and in proliferative inflammatory atrophy (PIA) of the prostate. METHODS: Immunohistochemistry (IHC) was used to investigate the expression of COX-2 in prostate epithelium. The relationships between COX-2 expression and inflammatory cells, proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67), and apoptosis (Bcl-2) were studied in 45 BPH samples. RESULTS: COX-2 expression was detected in prostate luminal epithelial cells in all 45 samples studied. The overall percentage of COX-2 positive glands was 7.5%, distributed as 0.2% positive glands in normal prostate tissue, 25.7% in postatrophic hyperplasia (PAH), and 11.9% in simple atrophy (SA). The highest proliferation index was found in COX-2 positive stained epithelium. COX-2 expression was associated with Bcl-2 immunostaining in atrophic lesions (P < 0.0001). T lymphocytes and macrophages were the predominant inflammatory cells related to the COX-2 expression in prostate epithelium. CONCLUSIONS: The data demonstrate that T lymphocytes and macrophages appeared to play an important role in the induction of COX-2 expression in prostate epithelium, which was associated with increased cell proliferation and possibly, due to overexpression of Bcl-2, apoptotic resistance. This suggests that pro-inflammatory cytokines released by adjacent inflammatory cells may induce COX-2 in the epithelial cells in prostate atrophic lesions. In addition, COX-2 expressing cells may be involved in the pathogenesis of prostate cancer.     

Cyclooxygenase-2 promotes prostate cancer progression

BACKGROUND: Cyclooxygenase (COX) -2, an inducible isoform of COX, has been observed to be expressed in prostate cancer. Several studies have reported that COX-2 overexpression is associated with carcinogenesis, cell growth, angiogenesis, apoptosis, and invasiveness in a variety of tumor types. METHODS: To investigate the function of COX-2 in prostate cancer directly, we stably transfected human full-length COX-2 cDNA into LNCaP cells (LNCaP-COX-2), which express low levels of endogenous COX-2. RESULTS: The level of COX-2 mRNA and protein and the COX activity in COX-2 LNCaP-COX-2 cells was significantly increased compared with parent and control-transfected cells. Overexpression of COX-2 increased both proliferation in vitro and tumor growth rate in vivo. However, the pro-tumor effect was neither associated with changes of androgen receptor (AR) expression level nor AR activity. Furthermore, addition of the major metabolites of COX-2-mediated arachidonic acid metabolism did not alter the proliferation of LNCaP-COX-2 cells in vitro. LNCaP-COX-2 cells had increased secretion of vascular endothelial growth factor (VEGF) protein, suggesting that angiogenesis induced by COX-2 stimulates tumor growth in vivo. CONCLUSION: These data demonstrate that COX-2 contributes to prostate cancer progression and suggest that it mediates this effect, in part, through increased VEGF.     

Thrombospondin-1, vascular endothelial growth factor expression and their relationship with p53 status in prostate cancer and benign prostatic hyperplasia

OBJECTIVE: To evaluate the expression of thrombospondin-1 (TSP-1, a potent inhibitor of angiogenesis) and vascular endothelial growth factor (VEGF, an important angiogenic factor in solid tumours) in prostate cancer, and their relationship with p53 status. PATIENTS AND METHODS: Using immunohistochemistry, the expression of VEGF, TSP-1 and p53 was assessed in 82 archival tissue specimens from 23 patients with benign prostatic hyperplasia (BPH), 22 with localized prostate cancer and 37 with metastatic prostate cancer. Seven of the last group had received androgen deprivation therapy. The relationship between the expression of VEGF, TSP-1 and p53 status was also evaluated with tumour grade and stage in patients with prostate cancer. RESULTS: The seven patients receiving hormonal treatment were excluded from the analysis because androgen deprivation significantly increased TSP-1 and decreased VEGF expression (both P < 0.01). Immunohistochemical analysis showed significantly higher VEGF and significantly lower TSP-1 expression (both P < 0.01) in prostate cancer than in BPH tissues. There was also significantly higher VEGF and significantly lower TSP-1 expression (both P < 0.05) in tissues from metastatic than localized prostate cancer. There was no significant correlation between VEGF or TSP-1 expression and Gleason score, but a significant inverse correlation between TSP-1 and VEGF expression. There was a significant association between VEGF expression and p53 status (P < 0.05), but TSP-1 expression was not associated with p53 status. CONCLUSIONS: Angiogenic factors, including VEGF and TSP-1, might be important in the development and progression of prostate cancer. These changes seem to be influenced by p53 status. Identifying the angiogenic factors involved in prostate cancer might lead to the development of diagnostic or therapeutic strategies based on anti-angiogenesis.     

环氧化酶2和血管内皮细胞生长因子在前列腺癌组织中的表达及意义

目的:探讨环氧化酶2(COX2)和血管内皮细胞生长因子(VEGF)在前列腺癌中的表达及临床意义。方法:采用免疫组化SP法检测40例前列腺癌和10例良性前列腺增生(BPH)组织中COX2和VEGF的表达。结果:前列腺癌组织中COX2和VEGF的阳性表达均明显高于BPH(P<0.01);COX2和VEGF在前列腺癌中的表达水平与其病理分级和临床分期均呈正相关(P均<0.05);前列腺癌中COX2表达水平和VEGF的表达水平相关(χ2=4.768,P=0.01)。结论:COX2可能诱导VEGF的表达而促进前列腺癌肿瘤血管的生成和侵袭转移。COX2和VEGF是检测前列腺癌的较好分子标志物,可望用于前列腺癌的辅助诊断和预后判断。     

The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer

OBJECTIVE: To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS: The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS: Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS: TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.     

Altered expression of genes regulating angiogenesis in experimental androgen-independent prostate cancer

BACKGROUND: The aim of this study was to investigate how the expression of genes regulating angiogenesis is altered when prostate cancer cells progress into androgen-independency. METHODS: A gene array specific for angiogenesis was used to compare the human prostate cancer cell line LNCaP (androgen-dependent) with its more angiogenic and tumorigenic subline LNCaP-19 (androgen-independent). Results were verified with real-time RT-PCR, and further investigations were focused on the angiogenesis inhibitor a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Expression of ADAMTS1 was investigated in vitro as well as in subcutaneous tumors with real-time RT-PCR and Western blotting. Microvessel density (MVD), versican proteolysis and protein levels of TIMP-2 and TIMP-3, known as ADAMTS1 inhibitors, were also analyzed in tumor xenografts. RESULTS: The gene array revealed decreased expression of ADAMTS1, ephrin-A5, fibronectin 1, and neuropilin 1 in LNCaP-19 compared to LNCaP, while expression of midkine and VEGF were increased. Further studies showed that mRNA and protein levels of ADAMTS1 were significantly lower in LNCaP-19 compared to LNCaP, both in vitro and in subcutaneous tumors. The amount of ADAMTS1 correlated negatively with MVD, but no relation was found between ADAMTS1 and versican proteolysis. CONCLUSIONS: Expression of several genes associated with angiogenesis was altered during transition into androgen-independency. Among these, a significant decrease was found for ADAMTS1, whose expression inversely correlated with MVD. Its role in progression of prostate cancer needs further investigation, but this inhibitor of angiogenesis could be an interesting candidate for future anti-angiogenic therapy.     

Tumor angiogenesis is associated with progression after radical prostatectomy in pT2/pT3 prostate cancer

BACKGROUND: The clinical relevance of tumor angiogenesis has been investigated in several human tumor types. Angiogenesis (measured as microvessel density; MVD) was recently correlated with tumor stage, grade, and clinical course in prostate cancer (PC). However, considerable controversy remains concerning the prognostic value of angiogenesis in PC. METHODS: We examined MVD in primary PCs to further establish the prognostic relevance of angiogenesis in this tumor entity. In 98 paraffin-embedded PCs of various stages, 5 prostate adenomas, and 20 normal prostate tissues, MVD was determined immunohistochemically using a polyclonal antibody against factor VIII. The findings were correlated with the clinical data of the patients. RESULTS: Normal prostate tissue and prostate adenomas had a low MVD. In PC, MVD increased significantly with tumor stage and grade (P < 0.001). The Wilcoxon rank statistics showed significant differences for MVD (P < 0.0001), tumor stage (P < 0. 0027), and grade (P < 0.0001), but not for preoperative prostate-specific antigen values in PC patients with and without tumor progression subsequent to treatment, respectively. Importantly, multivariate survival analysis revealed that MVD and tumor grade were the only independent markers for progression in prostate carcinoma. CONCLUSIONS: In this study, tumor angiogenesis measured by MVD was associated with a dismal pathologic appearance and a negative clinical prognosis in PC after radical prostatectomy.     

经尿道前列腺电切术中出血与前列腺增生组织MVD、VEGF的关系

目的通过检测经尿道前列腺电切（TURP）术后前列腺增生组织血管内皮生长因子（VEGF）的蛋白表达、微血管密度（MVD）,对照术中出血量,探讨其间的相关性。方珐采用免疫组化方法,对徐州市第二人民医院2005年2月～2007年6月的100例TuRP组织按前列腺体积进行分组,按病理学类型分别进行血管标记和染色检测MVD及VEGF的表达。采用氰化高铁血红蛋白比色计算术中出血量,并与病理学分类及MVD、VEGF进行比较。结果1。0例患者中,同体积前列腺术中出血量与MVD、VEGF呈明显相关性。MVD、VEGF高表达者术中出血多（P〈0．05）。随体积增大（〉60mL）,前列腺增生病理类型发生变化,但术中出血量与前列腺体积大小不一致,而与MVD、VEGF表达呈正相关。结论TURP术中出血量与前列腺病理学类型相关,组织MVD、VEGF表达高者,术中出血量多。     

肝细胞肝癌中COX-2、VEGF表达与肿瘤血管生成及其临床病理意义

目的　研究环氧合酶- 2 (COX- 2 )、血管内皮生长因子(VEGF)蛋白表达水平和肿瘤血管形成在肝细胞肝癌(HCC)组织中的临床病理意义。方法　应用免疫组化方法检测4 4例肝细胞癌患者手术切除石蜡包埋标本的COX- 2、VEGF的蛋白表达,抗CD34单克隆抗体显示血管内皮细胞,根据CD34阳性的血管内皮细胞计数来测定肿瘤微血管密度(MVD)。结果　高分化HCC中COX- 2蛋白表达显著高于中分化和低分化HCC(P<0 .0 5 ) ;转移组COX- 2蛋白表达显著高于无转移组(P<0 .0 1)。转移组VEGF蛋白表达显著高于无转移组(P<0 .0 1) ;无包膜HCC中VEGF蛋白表达显著高于有包膜HCC(P<0 . 0 5 )。转移组MVD显著高于无转移组(P<0 .0 1)。COX- 2和VEGF及VEGF和MVD之间表达的强弱呈强正相关(分别r=0 .6 2 6 1,r=0 .6 0 97;均P<0 .0 0 1) ;COX- 2和MVD之间无相关性(r=1.30 4 ,P>0 .0 5 )。结论　COX- 2的过度表达可能与高分化HCC致癌有关;COX- 2及VEGF均与肝癌的转移相关;COX- 2表达与VEGF表达可能有协同效应,共同促进了肿瘤血管的生成,从而促进HCC的生长、浸润和转移。     

COX-2、Ki-67联合检测对良恶性前列腺病变鉴别诊断的价值分析

目的 探讨环氧合酶-2(COX-2)、细胞增殖核抗原Ki-67(Ki-67)联合检测对良恶性前列腺病变的鉴别诊断价值。方法 选取2017年1月至2019年6月本院收治的168例良恶性前列腺病变患者,将其中83例前列腺癌(PCa)患者设为PCa组,85例良性前列腺病变患者[良性前列腺增生（BPH）患者40例、前列腺上皮内瘤(PIN)患者45例]设为BPH+PIN组。检测两组前列腺病变组织的COX-2、Ki-67表达水平;分析前列腺组织中的COX-2、Ki-67表达水平与PCa临床病理特征的关系;采用受试者工作特征（ROC）曲线评价前列腺病变组织COX-2、Ki-67 mRNA表达水平对PCa的诊断和鉴别价值。结果 PCa组患者的前列腺组织中COX-2、Ki-67 mRNA及蛋白阳性表达率水平均高于BPH+PIN组（均P<0.001）;PCa组患者的前列腺组织中COX-2、Ki-67表达水平与临床分期、远处转移、淋巴结转移、浸润深度、分化程度有明显相关性（均P<0.05）,与年龄、组织类型无相关性（均P>0.05）;前列腺病变组织的COX-2、Ki-67 mRNA诊断PCa的曲线下面积（AUC）分别为0.885、0.868,灵敏度分别为83.13%、78.31%,特异度分别为91.76%、92.94%;两者联合鉴别PCa的灵敏度（95.18%）高于两项单独检测,而特异度（90.59%）低于两项单独检测。结论 前列腺病变组织中的COX-2联合Ki-67对PCa具有较高的诊断价值,可提高诊断灵敏度,且具有较高准确度,有助于临床鉴别良恶性前列腺病变。