1.Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis, cirrhosis and hepatocellular carcinoma.
Soon Ha KWON ; Soung Won JEONG ; Jae Young JANG ; Ji Eun LEE ; Sae Hwan LEE ; Sang Gyune KIM ; Young Seok KIM ; Young Deok CHO ; Hong Soo KIM ; Boo Sung KIM ; So Young JIN
Clinical and Molecular Hepatology 2012;18(3):287-294
BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC. METHODS: The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29). RESULTS: The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3+/-1.9 (mean+/-SD), 4.2+/-1.7, 5.5+/-1.0, and 3.4+/-2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9+/-0.8, 1.5+/-0.7, 1.8+/-0.9, and 1.6+/-1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001). CONCLUSIONS: The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.
Adult
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Aged
;
Carcinoma, Hepatocellular/*metabolism/mortality/pathology
;
Cyclooxygenase 2/*metabolism
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Female
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Hepatitis, Chronic/*metabolism/mortality/pathology
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Humans
;
Immunohistochemistry
;
Kaplan-Meier Estimate
;
Liver Cirrhosis/*metabolism/mortality/pathology
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Liver Neoplasms/*metabolism/mortality/pathology
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Male
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Middle Aged
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Vascular Endothelial Growth Factor A/*metabolism
2.Cyclooxygenase-2 and p53 Expression as Prognostic Indicators in Conventional Renal Cell Carcinoma.
Dae Sung CHO ; Hee Jae JOO ; Dong Keun OH ; Ji Hun KANG ; Young Soo KIM ; Kyi Beom LEE ; Se Joong KIM
Yonsei Medical Journal 2005;46(1):133-140
The aim of this study was to investigate the relationship of cyclooxygenase (COX) -2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p= 0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p < 0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.
Carcinoma, Renal Cell/*metabolism/mortality/pathology
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Humans
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Kidney Neoplasms/*metabolism/mortality/pathology
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Prognosis
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Prostaglandin-Endoperoxide Synthase/*metabolism
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Protein p53/*metabolism
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Tumor Markers, Biological/*metabolism
3.Prognostic value of E-cadherin, CD34 in the patients with hepatocellular carcinoma.
Li-qun WU ; Yun LU ; Hua-jun LU ; Bin ZHANG ; Jin-yong YANG ; Xiang MA
Chinese Journal of Surgery 2006;44(11):774-777
OBJECTIVETo study the expression of E-cadherin and CD34 in the tissues of hepatocellular carcinoma (HCC), to discuss the relationship between them and the clinical pathology and evaluate the prognosis of HCC patients.
METHODSThe expression of E-cadherin and CD34 in HCC tissues of 41 patients were examined by two-step methods of PV-6000 of immunohistochemistry. Clinical-pathological data, tumor recurrent rate and survival rate after hepatectomy were recorded and analyzed.
RESULTSThe positive expression rate was observed in 48.78% for E-cadherin and 100% for CD34. The decreased E-cadherin expression were significantly associated with larger tumor, the high-dangerous group with invasion and poor differentiation of HCC tissues (chi(2) = 4.1881, 4.8118, 6.2695, P < 0.05). In the group with negative-expression of E-cadherin, the percent of tumor recurrence within 2 years after hepatectomy was higher and the rate of 5 years survival was significantly lower than the positive-expressed group. A significant negative-correlation between the expression of CD34 and the patients' age and the invasion of tumor (t = 1.9371, 1.9010, P < 0.05) were found. There was no relationship between the expression of E-cadherin and CD34 in HCC tissues.
CONCLUSIONSThe patient with a negative-expression of E-cadherin in HCC tissues has a poor prognosis. No relationship between the expression of CD34 and tumor recurrence and patients' survival and no relationship between the expression of E-cadherin and CD34 was found.
Adult ; Aged ; Antigens, CD34 ; metabolism ; Cadherins ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Survival Rate
4.Clinicopathological features and prognosis of renal cell carcinoma with sarcomatoid differentiation.
Yanxia JIANG ; Guoqiang SU ; Wenjuan YU ; Jingjing LI ; Qing LU ; Yujun LI ; Wei ZHANG
Chinese Journal of Oncology 2015;37(11):823-826
OBJECTIVETo study the clinicopathological features and prognosis of renal cell carcinoma with sarcomatoid differentiation (RCCS).
METHODSThe clinical data and pathological materials of 18 RCCS cases were retrospectively reviewed.The follow up data were available in 13 RCCS cases, and were compared with the follow up data of 20 cases of clear cell renal cell carcinoma (RCC).
RESULTSThe 18 RCCS patients included 14 males and 4 females, and were 49-79 years old (mean age: 62 years old). On gross examination, the tumor size was 3-19 cm in diameter (mean diameter: 9.8 cm). Histologically, all tumors were composed of a mixture of typical RCC with sarcomatoid component, including 9 clear cell RCC, 3 chromophobe RCC and one papillary RCC. The sarcomatoid components included 9 cases of fibrosarcoma, 3 cases of leiomyosarcoma, 5 cases of malignant fibrous histocytoma and one case of undifferentiated sarcoma. Immunohistochemistry showed that the sarcomatoid components were strongly vimentin-positive in 18 cases, and one or more epithelial markers (EMA, AE1/AE3, CK7, CK18) were expressed to varying degrees in 14 cases, but the high-molecular weight keratin 34βE12 was scarcely expressed. The sarcomatoid components presented positive expressions of CAIX in 88.9% (16/18) and CD10 in 72.2% (13/18) cases. Among the 18 RCCS patients, 13 patients were followed-up: 9 patients died in 1-25 months after the surgery, of which 5 cases died of lung or bone metastasis, and 4 patients died of systemic failure. The twenty RCC cases without sarcomatoid differentiation were followed up for 3-65 months after the surgery, and the majority of them was alive uneventfully except for 2 cases who died of lung or bone metastasis of the tumor. The Kaplan-Meier survival analysis showed that the median survival time of the 18 RCCS patients was 8 months, while that of the 20 RCC cases without sarcomatoid differentiation was 62 months (P<0.001).
CONCLUSIONSThe presence of sarcomatoid differentiation in renal cell carcinoma indicates highly aggressive behavior and poor prognosis. The positive expressions of the immune markers CAIX and CD10 may play important roles in the transformation from renal cell carcinoma to sarcomatoid component.
Aged ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; metabolism ; mortality ; pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Kidney Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Sarcoma ; metabolism ; mortality ; pathology ; Tumor Burden
5.Clinicopathological Significance of Expression of Tspan-1, Jab1 and p27 in Human Hepatocellular Carcinoma.
Li CHEN ; Daiyue YUAN ; Gui lan WANG ; You WANG ; Yuan Yuan WU ; Jianwei ZHU
Journal of Korean Medical Science 2010;25(10):1438-1442
The aim of this study was to investigate the expression of Tspan-1, Jab1 and p27 in human hepatocellular carcinoma (HCC) and their clinicopathological significance. The expression of Tspan-1, Jab1 and p27 was detected in HCC tissues, the tissues around cancer (76 cases), and the normal tissues around the liver hemangiomas (10 cases). The overexpression of Tspan-1 and Jab1 was found in HCC tissues, positively correlated with clinical stage and negatively correlated with survival rate. The expression of p27 was found inversely linked to which of Tspan-1 and Jab1. In conclusion, the expression of Tspan-1, Jab1 and p27 is significantly associated with development of HCC. Overexpression of Tspan-1 and Jab1 suggests poor prognosis but overexpression of p27 may expect good prognosis for patients with HCC.
Adult
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Aged
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Carcinoma, Hepatocellular/metabolism/mortality/*pathology
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Cyclin-Dependent Kinase Inhibitor p27/*metabolism
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Female
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Humans
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Intracellular Signaling Peptides and Proteins/*metabolism
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Liver Neoplasms/metabolism/mortality/*pathology
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Male
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Membrane Proteins/*metabolism
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Middle Aged
;
Peptide Hydrolases/*metabolism
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Prognosis
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Survival Rate
6.Prognostic Significance of Angiogenesis by Chalkley Counting in Node Negative Cancer of the Ampulla of Vater.
Joon Seong PARK ; Hyun Ki KIM ; Soon Won HONG ; Jae Keun KIM ; Dong Sup YOON
Journal of Korean Medical Science 2012;27(5):495-499
Angiogenesis is essential for tumor growth and metastasis. Currently, the Chalkley assay with CD34 immunostaining is the proposed standard method for angiogenesis quantification in solid tumor sections. The purpose of this study was to evaluate the expression of CD34 and its prognostic significance using the Chalkley method in node negative carcinoma of the ampulla of Vater. Between January 1997 and December 2006, 56 node negative patients who had curative resection for carcinoma of the ampulla of Vater were retrospectively reviewed. The Chalkley count was expressed as the mean value of the three counts for each tumor and further divided into two groups according to the mean value of the Chalkley count: low < 4 or high > or = 4. The mean Chalkley count value was 4.0 (+/- 3.1). In the low Chalkley group, the 1- and 3-yr recurrence rates were 18.3%, 47.6% respectively; in the high Chalkley group, the 1- and 3-yr recurrence rates were 26.5% and 60.6% respectively. Only high Chalkley count had statistical significance as a factor in recurrence of node negative ampulla of Vater carcinoma. Assessment of angiogenesis may have an important role in the prognostic evaluation of node negative cancer of the ampulla of Vater.
Adult
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Aged
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Ampulla of Vater/metabolism/*pathology
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Antigens, CD34/metabolism
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Carcinoma/metabolism/mortality/*pathology
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Common Bile Duct Neoplasms/metabolism/mortality/*pathology
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Disease-Free Survival
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Female
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Humans
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Lymphatic Metastasis
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Male
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Middle Aged
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*Neovascularization, Pathologic
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Predictive Value of Tests
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Prognosis
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Recurrence
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Retrospective Studies
7.Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis.
Sheng-Li YANG ; Quan-Guang REN ; Lu WEN ; Jian-Li HU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(3):321-327
Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
Adenocarcinoma
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diagnosis
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genetics
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mortality
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pathology
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Biomarkers, Tumor
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genetics
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metabolism
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Carcinoma, Non-Small-Cell Lung
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diagnosis
;
genetics
;
mortality
;
pathology
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Carcinoma, Squamous Cell
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diagnosis
;
genetics
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mortality
;
pathology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit
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genetics
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metabolism
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Lung Neoplasms
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diagnosis
;
genetics
;
mortality
;
pathology
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Lymphatic Metastasis
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Neoplasm Grading
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Neoplasm Staging
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Odds Ratio
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Prognosis
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Receptor, Epidermal Growth Factor
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genetics
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metabolism
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Survival Analysis
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Vascular Endothelial Growth Factor A
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genetics
;
metabolism
8.Expression and significance of MCM2, Ki-67 and Rb protein in laryngeal squamous cell carcinomas.
Kaigui CAI ; Ying LUO ; Lixiang LI ; Yuehui LIU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(9):425-428
OBJECTIVE:
To investigate the expression of MCM2, Ki-67 and Rb and its biological characteristic in human laryngeal squamous cell carcinomas(LSCC).
METHOD:
The expression of MCM2 protein and Rb protein were detected in 60 cases of LSCC, 10 cases of precarcinoma, 10 cases of vocal cord polyps and 10 cases of normal laryngeal tissues, and Ki-67 protein were detected in 60 cases of LSCC and 10 cases of normal laryngeal tissues by Elivision plus immunohistochemical staining, and analyze their relations with clinicopathological characteristics.
RESULT:
The positive expression rate of MCM2 in LSCC was significantly higher than that in precarcinoma and normal laryngeal tissues (P < 0.05), and was positively correlated with pathological grades, clinical stages and lymph node metastases (P < 0.05) of LSCC. The positive expression rate of Rb protein in LSCC was significantly lower than that in precarcinoma and normal laryngeal tissues (P < 0.05). The expression level of MCM2 in LSCC was negatively corelated with Rb (r = -0.542, P < 0.05), the expression level of Ki-67 in LSCC (76.67%) was significantly higher than that in normal laryngeal tissues (30.00%) (P < 0.01) and the expression level of MCM2 in LSCC was positively corelated with Ki-67(r = 0.596, P < 0.01). The LI of MCM2 in the 3-year survival rate of LSCC was significantly lower than that in Ki-67 (P < 0.05).
CONCLUSION
Over expression of MCM2 and loss of Rb protein were related to the carcinogenesis and development of LSCC. The determination of MCM2 can be an index for estimating the level of malignancy and prognosis of LSCC.
Carcinoma, Squamous Cell
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metabolism
;
mortality
;
pathology
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Cell Cycle Proteins
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Humans
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Ki-67 Antigen
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metabolism
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Laryngeal Neoplasms
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metabolism
;
mortality
;
pathology
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Larynx
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metabolism
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Lymphatic Metastasis
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Minichromosome Maintenance Complex Component 2
;
metabolism
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Neoplasm Proteins
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metabolism
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Polyps
;
metabolism
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Precancerous Conditions
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metabolism
;
mortality
;
pathology
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Retinoblastoma Protein
;
metabolism
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Survival Rate
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Vocal Cords
;
metabolism
9.Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma.
Hyun Young WOO ; Ae Lyoung MIN ; Jong Young CHOI ; Si Hyun BAE ; Seung Kew YOON ; Chan Kwon JUNG
The Korean Journal of Hepatology 2011;17(1):12-18
BACKGROUND/AIMS: E-cadherin is involved in intercellular binding and cellular polarity formation. Snail is a key regulator of the epithelial-mesenchymal transition and is closely associated with tumor invasiveness due to its ability to suppress E-cadherin expression. We investigated the expressions of E-cadherin and Snail in hepatocellular carcinoma (HCC) tissue to determine the clinical significance of these proteins in HCC. METHODS: Immunohistochemistry was used to examine the expressions of E-cadherin and Snail in resected tissues from 59 patients diagnosed with HCC. We also evaluated the relationship between the expressions of these two molecules in HCC tissue and clinicopathologic factors in the patients. RESULTS: Immunohistochemistry showed that Snail was stained in 20.3% of the HCC tissues and 3.4% of noncancerous tissues. Snail was not stained in the area of E-cadherin expression. The expression of Snail in the HCC tissue was associated with poorly differentiated HCC (P=0.028). The expression of Snail without E-cadherin staining in HCC tissue was significantly associated with postoperative HCC recurrence (P=0.013). CONCLUSIONS: The expression of Snail in HCC tissue was associated with decreased expression of E-cadherin and poorly differentiated HCC. The expression of Snail without E-cadherin staining in HCC was associated with postoperative recurrence.
Adult
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Aged
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Aged, 80 and over
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Cadherins/metabolism
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Carcinoma, Hepatocellular/metabolism/mortality/*pathology
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Female
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Humans
;
Immunohistochemistry
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Liver Neoplasms/metabolism/mortality/*pathology
;
Male
;
Middle Aged
;
Recurrence
;
Survival Rate
;
Transcription Factors/*metabolism
10.The clinical significance of vascular endothelial growth factor and intercellular adhesion molecule-1 expression in non-small cell lung cancer.
Hong-wei ZHANG ; Lin ZHANG ; Jing-han CHEN ; Jia-jun DU
Chinese Journal of Surgery 2005;43(6):354-357
OBJECTIVETo investigate the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1), and their relationship to behaviors of the non-small-cell lung cancer.
METHODSThe study included 86 patients with non-small-cell lung cancer. A rapid immunohistochemical method (streptoavidin-peroxidase, SP) was used to detect VEGF and ICAM-1 expression. All patients were treated surgically and without preoperative radio- or chemotherapy.
RESULTSThe positive expression of VEGF was significantly correlated with the lymph node metastasis, TNM stage, prognosis and hematogenous tumor metastasis positively, but ICAM-1 was negatively. For patients with positive expression of VEGF and negative expression of ICAM-1, the 5-year survival rate was the lowest in all patients.
CONCLUSIONSThe expression of VEGF and ICAM-1 correlates with the malignant behavior of non-small-cell lung cancer. Examination of VEGF and ICAM-1 in non-small-cell lung cancer may help to evaluate its intensity of lymph node metastasis, TNM stage and prognosis. VEGF and ICAM-1 may play an important role in the development and metastasis of non-small-cell lung cancer.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; pathology ; Female ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism