BACKGROUNDHuman U three protein 14a (hUTP14a) promotes p53 degradation. Moreover, hUTP14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP14a in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate hUTP14a expression and its prognostic value in HCC.

METHODSThe hUTP14a expression was evaluated using immunohistochemistry (IHC) in HCC tissue specimens. The correlations between hUTP14a expression and clinicopathological variables were analyzed. The Kaplan-Meier method was used to analyze the association between hUTP14a expression and survival. Independent prognostic factors associated with overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox proportional-hazards regression model.

RESULTSThe IHC data revealed that the hUTP14a positivity rate in HCC tissue specimens was significantly higher than that in nontumorous tissue specimens (89.9% vs. 72.7%, P < 0.05). The hUTP14a expression was detected in both the nucleolus and the cytoplasm. The positivity rate of nucleolar hUTP14a expression in HCC tissue specimens was higher than that in the nontumorous tissue specimens (29.3% vs. 10.1%, P < 0.05). No significant difference was found between HCC and nontumorous tissue specimens of cytoplasmic hUTP14a expression (60.6% vs. 62.6%, P > 0.05). In addition, no significant correlation was found between nucleolar hUTP14a expression and other clinicopathological variables. The 5-year OS and DFS rates in patients with positive nucleolar hUTP14a expression were significantly lower than those in patients with negative hUTP14a expression (P = 0.004 for OS, P = 0.003 for DFS). Multivariate analysis showed that nucleolar hUTP14a expression was an independent prognostic factor for OS (P = 0.004) and DFS (P < 0.001).

CONCLUSIONSThe positivity rate of hUTP14a expression was significantly higher in HCC specimens. Positive expression of nucleolar hUTP14a might act as a novel prognostic predictor for patients with HCC.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Ribonucleoproteins, Small Nucleolar ; genetics ; metabolism

PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma/*metabolism/*mortality/surgery ; Cystectomy ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Muscles/pathology ; Neoplasm Invasiveness ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptor, Fibroblast Growth Factor, Type 1/*metabolism ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Retrospective Studies ; Survival Rate ; Urinary Bladder Neoplasms/*metabolism/*mortality/surgery ; Urothelium/pathology

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 ; diagnosis ; genetics ; mortality ; pathology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; mortality ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; mortality ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Lung Neoplasms ; diagnosis ; genetics ; mortality ; pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Survival Analysis ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

BACKGROUND/AIMS: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. RESULTS: FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. CONCLUSIONS: FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/mortality/*pathology ; Female ; Hepatectomy ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/metabolism/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Protein Isoforms/metabolism ; Receptors, Fibroblast Growth Factor/*metabolism ; Young Adult

OBJECTIVETo investigate the clinicopathological features and prognosis of primary squamous cell carcinoma of the breast and to improve the diagnosis, treatment and prognosis of this disease.

METHODSThe clinicopathological data of 22 patients with primary squamous cell carcinoma of the breast treated in our hospital between January 1985 and January 2011 were retrospectively reviewed. The correlation between age, tumor size, axillary node status, treatment modality and prognosis was statistically analyzed.

RESULTSAll the 22 patients were female and their median age was 56 years.The average tumor diameter was 3.6 cm.The diagnosis was confirmed by histopathology. The positive rates of expression of ER, PR and HER-2 of the breast cancers were 9. 1%, 9. 1% and 33. 3%, respectively. In follow-up visits, recurrence or metastasis was found in 5 patients and they all died of it. The median overall survival of the 22 patients was 60 months and their overall 5-year survival rate was 73.6%. Univariate analysis showed that the tumor maximum diameter (P = 0.024) and axillary lymph node status (P = 0.022) were impact factors, while menopause, chemotherapy and radiotherapy were not. Cox multivariate analysis showed that the tumor size (P = 0.021) and axillary lymph node status (P = 0.037) were independent prognostic factors for primary squamous cell carcinoma of the breast.

CONCLUSIONSPrimary squamous cell carcinoma of the breast is a rare entity and lack of specific clinical features. Axillary node status is an independent prognostic factor.

Analysis of Variance ; Axilla ; Breast Neoplasms ; metabolism ; mortality ; pathology ; Carcinoma, Squamous Cell ; metabolism ; mortality ; pathology ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Tumor Burden

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

OBJECTIVETo detect the expression of interleukin-17A(IL-17A) in hepatocellular carcinoma (HCCs) tissues, and to analyze its relationship with clinicopathological characteristics and epithelial-mesenchymal transition (EMT).

METHODSThe expression of IL-17A, E-cadherin, vimentin proteins and Snail mRNA were detected by immunohistochemistry and in situ hybridization histochemistry in the hepatocellular carcinoma (HCC) tissues of 74 patients.

RESULTSIL-17A staining was detected in 54.1% (40/74) specimens of human HCCs, but only 25.0% (5/20) in corresponding peritumoral tissues (P<0.05). The positive rate of IL-17A expression in HCC patients with grade III+IV and UICC stage III+IV tumors was significantly higher than those with grade I+II and UICC stage I+II tumors. The expression of IL-17A was positively correlated with portal vein tumor thrombus and microvascular invasion (all P<0.05). The 1- and 2-year recurrence-free survival rates were 27.6% and 17.2% in the patients with positive IL-17A expression, but 79.3% and 58.5% in IL-17A-negative HCCs. The 1- and 2-year overall survival rates were 69.0% and 27.8% in the cases with positive IL-17A expression, while 91.3% and 87.0% in IL-17A-negative cases. Patients with IL-17A-positive HCCs showed significantly shorter recurrence-free and overall survival compared with the patients with IL-17A-negative HCCs (P<0.05). Multivariate analysis indicated that IL-17A expression was an independent factor for recurrence-free and overall survival of HCCs. IL-17A-positive HCCs were characterized by increased expression of vimentin (r=0.492, P<0.01) or Snail (r=0.410, P<0.05) and loss of E-cadherin expression (r=-0.404, P<0.05).

CONCLUSIONSOur results suggest that IL-17A is closely related to epithelial-mesenchymal transition in hepatocellular carcinoma. IL-17A-positive hepatocellular carcinoma demonstrates more aggressive biological behavior, and IL-17A may serve as a potential prognostic marker for this cancer.

Cadherins ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; physiopathology ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Humans ; Immunohistochemistry ; Interleukin-17 ; metabolism ; Liver Neoplasms ; metabolism ; mortality ; pathology ; physiopathology ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Recurrence, Local ; Prognosis ; RNA, Messenger ; metabolism ; Snail Family Transcription Factors ; Survival Rate ; Transcription Factors ; genetics ; metabolism ; Vimentin ; genetics ; metabolism

OBJECTIVE: To evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC). MATERIALS AND METHODS: The study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors. RESULTS: Thirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months). CONCLUSION: Even in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.
Adult ; Aged ; Alanine Transaminase/metabolism ; Aspartate Aminotransferases/metabolism ; Carcinoma, Hepatocellular/mortality/*pathology/therapy ; Chemoembolization, Therapeutic/adverse effects ; Female ; Hepatic Encephalopathy/etiology ; Humans ; Length of Stay ; Liver Neoplasms/mortality/*pathology/therapy ; Liver Transplantation ; Male ; Middle Aged ; Proportional Hazards Models ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Tumor Burden

BACKGROUND/AIMS: The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored. RESULTS: The interleukin-1-beta-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues. CONCLUSIONS: The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.
Adolescent ; Adult ; Aged ; Carcinoma, Hepatocellular/*diagnosis/mortality/pathology ; Down-Regulation ; Female ; Hep G2 Cells ; Humans ; Hydroxyprostaglandin Dehydrogenases/*metabolism ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/*diagnosis/mortality/pathology ; Male ; Middle Aged ; Prognosis ; Young Adult

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.
CA-19-9 Antigen/metabolism ; Carcinoma, Hepatocellular/mortality/pathology/radiography ; Cholangiocarcinoma/mortality/pathology/radiography ; Humans ; Liver Neoplasms/mortality/pathology/*radiography ; Magnetic Resonance Imaging ; Phenotype ; Risk Factors ; Survival Analysis ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis