Interleukin-8 is a prognostic indicator in human hilar cholangiocarcinoma

Interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and neovascularization have been implicated to be associated with biological processes, especially cancer progression. However, few studies have investigated the role of IL-8 in human hilar cholangiocarcinoma. In this study we detected the expression of IL-8 combined with MMP-9 and microvessel density (MVD) in hilar cholangiocarcinoma to evaluate their clinicopathological significance and prognostic value. A total of 62 patients with hilar cholangiocarcinoma who underwent curative surgery were enrolled in this study. The expression of IL-8, MMP-9 and MVD were examined immunohistochemically. The correlation of IL-8 with MMP-9 expression, MVD, clinicopathological features and survival time of patients were then analyzed. Expression of IL-8 was observed in 56.5% tumors, which was related to advanced TNM stage (P = 0.026) and tumor recurrence (P = 0.018). IL-8 had a positive correlation with MMP-9 expression and MVD. Furthermore, patients with high IL-8 expression had a significantly shorter overall survival than those with low IL-8 expression (P = 0.01). Multivariate analysis confirmed IL-8 as an independent prognostic factor (P = 0.005). In conclusion, IL-8 expression significantly correlated with MMP-9 expression and MVD, and IL-8 was a valuable prognostic factor for human hilar cholangiocarcinoma.     

CA9 overexpression is an independent favorable prognostic marker in intrahepatic cholangiocarcinoma

The aim of this study is to evaluate the expression of carbonic anhydrase IX (CA9) and to identify its prognostic significance in intrahepatic cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9 overexpression was related to tumors with intraductal growth than mass forming or periductal infiltrative type. CA9 overexpression was more observed in tumors with well/moderate differentiation than poor differentiation and without lymph node metastasis. No significant correlation was observed in CA9 overexpression with tumor size, pT, stage and lymphovascular invasion. Intrahepatic cholangiocarcinomas with CA9 overexpression showed better overall survival than that without expression (P = 0.001). In multivariate analysis, lymph node metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence interval, 0.328-0.944) lower risk of death compared with those of no or weak expression. CA9 overexpression was related to histologic differentiation and an independent good prognostic factor.     

Metallothionein overexpression and its prognostic relevance in intrahepatic cholangiocarcinoma and extrahepatic hilar cholangiocarcinoma (Klatskin tumors)

Metallothionein is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. Metallothionein has been shown to regulate apoptosis and proliferation. Overexpression of metallothionein frequently occurs in human tumors and is related to prognosis as well as therapy response. However, metallothionein expression and its clinical relevance in cholangiocarcinoma have not been investigated. The present study aimed to analyze metallothionein over-expression and its possible prognostic impact in intrahepatic cholangiocarcinoma and hilar extrahepatic cholangiocarcinoma (Klatskin tumors). We investigated the relationship of immunohistochemically demonstrated metallothionein expression with various clinicopathological parameters in a series of 56 intrahepatic and 56 extrahepatic cholangiocarcinoma. In noncancerous bile duct epithelia metallothionein was only occasionally weakly expressed; strong metallothionein overexpression (>50% metallothionein -positive tumor cells) was noted in 7 (12.5%) of 56 intrahepatic cholangiocarcinoma and 14 (25%) of 56 Klatskin tumors, which was associated with poor clinical outcome in univariate Kaplan-Meier testing in both intrahepatic cholangiocarcinoma (P = .002) and Klatskin tumors (P = .034). Moreover, strong metallothionein expression was identified as an independent prognostic parameter in multivariate Cox regression analysis in both intrahepatic cholangiocarcinoma (P = .005) and Klatskin tumors (P = .035). In contrast, cholangiocarcinoma with a papillary phenotype (8/112; 7.1%) exhibited a significant lack of strong metallothionein expression in all 8 of 8 cases. Strong metallothionein expression is identified as an independent poor prognostic parameter, and determination of the metallothionein expression may serve as an additional tool for the therapeutic management of patients with cholangiocarcinoma. In comparison, lack of metallothionein expression seems to be associated with cholangiocarcinoma with a papillary phenotype, which is generally recognized to have a better prognosis.     

Overexpression of Prdx1 in hilar cholangiocarcinoma: a predictor for recurrence and prognosis

Prdx1 is an important member of peroxiredoxins (Prdxs) regulating various cellular signaling and differentiation. Prdx1 confers an aggressive survival phenotype of cancer cells and drug-resistance, yet its role in hilar cholangiocarcinoma is not fully investigated. In present study, we detected the expression profile of Prdx1 in 88 hilar cholangiocarcinoma by tissue arrays and immunohistochemistry. Prdx1 level was down-regulated by specific Prdx1-shRNA in vitro and the possible mechanism was investigated. Overexpression of Prdx1 was observed in 53 of 88 cases (60.2%). Prdx1 expression was significantly associated with tumor invasion, nodal metastasis, advanced disease stage. Down-regulation of Prdx1 inhibited cell proliferation and colony formation of QBC939 cells and reduced the level of SNAT1 expression. Patients with Prdx1 overexpression had a shorter disease-free survival and overall survival than those without Prdx1 expression. Multivariate analysis showed that Prdx1 was an independent prognostic factor for patients with hilar cholangiocarcinoma. The data indicate that Prdx1 may contribute to the development and progression of hilar cholangiocarcinoma, partially through regulating SNAT1 expression, and may be used as a biomarker in predicting the outcome of patients with hilar cholangiocarcinoma.     

Preoperative serum CA19-9 levels is an independent prognostic factor in patients with resected hilar cholangiocarcinoma

To investigate the appropriate cutoff point of CA19-9 for prognosis and other potential prognostic factors that may affect survival of patients with hilar cholangiocarcinoma (HC) after radical surgery. 168 patients who had undergone radical surgery for hilar cholangiocarcinoma and resultant macroscopic curative resection (R0 and R1) were discreetly selected for analyses. Categorized versions were used in univariate model to determine the appropriate cutoff point of CA19-9. CA19-9 and other clinicopathologic factors were analyzed for influence on survival by univariate and multivariate methods. The strongest univariate predictor among the categorized preoperative CA19-9 measures was CA19-9 less than 150 IU/L (P = 0.000). In univariate analysis, tumor size, Bismuth-Corlette classification, portal vein invasion, Lymph node metastasis, resection margin and preoperative CA19-9 levels were identified as significant prognostic factors. In multivariable analysis, lymph node metastasis, resection margin and preoperative CA19-9 levels were independent prognostic factors. our results demonstrated that preoperative CA19-9 levels was also an independent prognostic factor for hilar cholangiocarcinoma, and the most discriminative cutoff point of CA19-9 for prognosis proved to be at 150 U/ml.     

Integrin αvβ6 predicts poor prognosis and promotes resistance to cisplatin in hilar cholangiocarcinoma

ObjectiveIntegrin αvβ6 is associated with an extremely aggressive cancer phenotype. However, little is known about the clinicopathological significance and prognostic value of integrin αvβ6 in human hilar cholangiocarcinoma.MethodsIn the present study, bioinformatics analysis demonstrated a significant increase of integrin β6 gene expression in cholangiocarcinoma tissues compared to non-tumorous tissues, which was further validated in clinical samples through RT-qPCR and western blotting analyses. Integrin αvβ6 was observed to be expressed in 48.6% of tumors, and its expression was related to a poor tumor differentiation (p = 0.002), lymph node metastasis (p<0.001) and advanced TNM stage (p=0.001). Furthermore, patients who were αvβ6-positive showed a significantly shorter overall survival period than those who were αvβ6-negative (p=0.004). Multivariate analysis confirmed that integrin αvβ6 was an independent prognostic factor (p=0.002). In addition, loss- and gain-of-function assays showed integrin αvβ6 not only played an important role in colony formation, but also protected cholangiocarcinoma cells from cisplatin-induced growth inhibition and apoptosis. ERK/MAPK signaling pathway was involved in integrin αvβ6-mediated resistance of cholangiocarcinoma cells to cisplatin.ConclusionsTaken together, the present findings revealed that integrin αvβ6 could serve as a potential prognostic predictor and contribute to cisplatin resistance, which might prove to be a promising target candidate for the clinical intervention of human hilar cholangiocarcinoma.     

Expression and Clinicopathological Significance of CD9 in Gastrointestinal Stromal Tumor

This study investigated the expression and clinicopathological significance of CD9 in gastrointestinal stromal tumor (GIST). Immunohistochemistry staining for CD9 was performed on tumor tissues from 74 GIST patients. The correlation with clinicopathological features, risk classification and prognosis was analyzed. CD9-positive staining comprised 59.5% (44/74) of the GIST patients. The CD9-positive expression rate of the sample was significantly associated with diameter (P = 0.028), mitotic counts (P = 0.035), risk classification (P = 0.018) and three-year recurrence-free survival (RFS) (P < 0.001). Cox proportional hazards regression (HR = 0.352; P = 0.015) showed that CD9 is an independent factor for post-operative RFS. The subgroup analysis showed that CD9 expression in gastric stromal tumor (GST) is significantly associated with diameter (P = 0.031), risk classification (P = 0.023) and three-year RFS (P = 0.001). The Cox proportional hazards regression (HR = 0.104; P = 0.006) also showed that CD9 is an independent factor for RFS of GST. However, CD9 expression does not have a statistically significant correlation with clinicopathological features, risk classification, and prognosis in non-GST. In conclusion, CD9 expression in GIST appears to be associated with the recurrence and/or metastasis of GIST patients, especially in GST, which may indicate the important role of CD9 in the malignant biological behavior and prognosis of GST.     

Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts

Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical resection. In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis.     

Expression and clinical significance of FOS-like antigen 1 in gastric adenocarcinoma

BackgroundThe overexpression of FOS-like antigen 1 (FOSL1) in several types of cancers was reported before. However, the expression and clinical significance of FOSL1 in gastric cancer (GC) have not been elucidated.Materials and methodsThe expression of FOSL1 in 105 cases of GCs was detected with immunohistochemistry, and the mRNA of FOSL1 was investigated with quantitative real-time polymerase chain reaction(qRT-PCR) in 15 pairs of GCs and tumor adjacent tissues. With Chi-square test or Fisher test, we analyzed the correlation between FOSL1 expression and clinicopathological factors. With univariate analysis, we evaluated the correlations between clinicopathological factors including FOSL1 and overall survival (OS) rates. With multivariate analysis, we identified the independent prognostic risk factors of GC.ResultsThe percentages of patients with low and high FOSL1 expression in our study accounted for 43.81% and 56.19%, respectively. The mRNA levels of FOSL1 in GCs were significantly higher than those in tumor adjacent tissues. FOSL1 expression was demonstrated to be significantly correlated with lymphatic invasion (P = 0.036) and TNM stage (P = 0.016). High expression of FOSL1 was significantly correlated with lower 5-year OS (P = 0.002), and FOSL1 expression was identified as an independent prognostic biomarker of GC (P = 0.001).ConclusionsFOSL1 is an independent prognostic biomarker of GC. Detecting FOSL1 expression could help stratify GC patients with high-risk and guide the precious treatment.     

Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast

Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.     

Clinicopathological correlation and prognostic significance of sonic hedgehog protein overexpression in human gastric cancer

Objectives: This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed. Methods: Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa. The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer. Results: In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P < 0.001), which was statistically correlated with age (P = 0.006), tumor differentiation (P < 0.001), depth of invasion (P = 0.042), pathologic staging (P = 0.017), and nodal metastasis (P = 0.019). We found no significant difference in both overall and disease free survival rates between Shh overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041). Conclusions: Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.     

Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman’s rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.     

Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma

It has been well accepted that p53 overexpression is associated with advanced stages of cancer. However, the prognostic role of p53 overexpression in esophageal squamous cell carcinoma (ESCC) remains unclear. To investigate the prognostic role of p53 overexpression in patients with ESCC, a retrospective cohort study of 136 ESCC patients was carried out. The expression of p53 protein in tumor tissues was investigated immunohistochemically. Positive expression of p53 protein was detected in 57 ESCC patients (41.9%). The p53 overexpression was associated with smoking (P < 0.001), tumor differentiation (P < 0.001), and tumor size (P < 0.001). In the Kaplan-Meier analysis, patients with p53 overexpression had significantly shorter overall survival than those patients with negative p53 expression (log-rank P < 0.001). Multivariable analysis by Cox regression model further showed that p53 overexpression was a significantly independent predictor of poorer overall survival (hazard ratio [HR] = 1.91; 95% confidence interval [95% CI] 1.03-3.54, P = 0.04). Thus, p53 overexpression is associated with poor prognosis in patients with early stage esophageal squamous cell carcinoma, and it’s a significantly independent predictor of poorer overall survival.     

Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma

Previously, gelatinases matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to be involved in melanoma invasion and progression. Also, overexpression of MMP-2 has been suggested to be linked to hematogenous metastasis in melanoma. This study was conducted to study the prognostic value of MMP-2 and MMP-9 in human melanoma. The expression of MMP-2 and MMP-9 immunoreactive protein was evaluated in 157 cases of primary melanomas. An immunohistochemical analysis using specific monoclonal antibodies for MMP-2 and MMP-9 on paraffin-embedded tissues was performed, and the immunostaining results were compared with the clinical course of melanoma. Overexpression of MMP-2 (>20% of malignant cells positive) was an independent prognostic marker for melanoma related death, with odds ratio of 2.6 (95% confidence interval, 1.32-5.07). The 10-year disease-specific survival rate was only 51% in patients with overexpression of MMP-2 protein compared with 79% in patients with a primary melanoma with low expression for MMP-2 (P = .001). Interestingly, male patients with a melanoma with overexpression of MMP-2 showed a 10-year disease-specific survival of only 41% compared with 77% in other male patients (P = .003). It is notable that the immunoreactive protein for MMP-9 in primary melanoma was not found to be of any prognostic importance. In the future, MMP-2 could be acknowledged as a new prognostic factor in melanoma. MMP-9, on the other hand, was not associated with the clinical course of melanoma. Based on the current data, MMP-2 could be evaluated as an inclusion factor for adjuvant studies especially in male melanoma patients.     

Prognostic relevance of cyclooxygenase-2 (COX-2) expression in Chinese patients with prostate cancer

Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression and metastasis. The present study was designed to investigate the clinicopathological and prognostic significance of COX-2 in Chinese patients with prostate cancer. Firstly, RT-PCR and Western blot assays were performed to detect the expression of COX-2 mRNA and protein in prostate cancer cell lines and 20 tissue samples (tumor or corresponding non-tumor). Next, immunohistochemistry was performed to detect the expression of COX-2 protein in 88 prostate cancer tissue samples. Finally, the correlation between COX-2 expression and clinicopathological factors and patient survival was evaluated. We found that the expression levels of COX-2 mRNA and protein showed significant difference among four prostate cancer cell lines. Moreover, the levels of COX-2 mRNA and protein were significantly higher in prostate cancer tissues than in corresponding non-tumor tissues. COX-2 staining was positive in the cytoplasm of prostate cancer cells. High-COX-2 expression was correlated with the Gleason score (P=0.009), tumor stage (P=0.012), and lymph-node status (P=0.036). Furthermore, patients with high-COX-2 expression showed lower disease-free (P=0.014) and overall survival (P=0.047) rates than those with low-COX-2 expression. Univariate and multivariate analyses suggested that the status of COX-2 protein expression was an independent prognostic indicator for patients’ survival. Taken together, higher COX-2 protein expression might provide an independent prognostic marker for Chinese patients with prostate cancer who have undergone surgery.     

Expression of molecular factors correlated with metastasis in small cell lung cancer and their significance

Distant metastasis continues to be a fatal threat to quality of life in patients with small cell lung caner (SCLC). The purpose of this work is to analyze the expressions of chemokine receptor four (CXCR4), matrix metalloproteinase-9 (MMP-9), transforming growth factor-b1 (TGF-β1), N-cadherin and vascular endothelial growth factor (VEGF) in small cell lung caner (SCLC), and to explore their correlations with the prognosis and metastasis. Sixty-five consecutive patients with stage I-III SCLC who received operation in our hospital from Jan 2003 to Oct 2009 were retrospectively analyzed. The expression of CXCR4 was found significantly correlated with bone metastasis (P = 0.004), and were marginally correlated with brain metastasis (P = 0.068) and lymph node metastasis (P = 0.085). The expression of MMP-9 was significantly associated with pathological staging (P = 0.048). Univariate analysis suggested surgical approach, clinical stage, lymph node metastasis were significantly associated with OS and PFS (P < 0.05), high expression of CXCR4 was significantly correlated with worse OS (P = 0.004) and PFS (P = 0.005). Multivariate analysis suggested surgical approach, TGF-β1, CXCR4 and lymph node metastasis were independent prognostic factor for PFS. In conclusion, High expression of CXCR4, MMP-9, TGF-β1 and VEGF were found in SCLC. High expression of MMP-9 was significantly associated with pathological staging, and high expression of CXCR4 was correlated with bone metastasis and also might correlate with brain metastasis. CXCR4 were independent prognostic factor for survival in SCLC and expanded samples should be further explored in the future.     

HER3 overexpression is a prognostic indicator of extrahepatic cholangiocarcinoma

Members of the HER (ERBB) receptor protein tyrosine kinase family play an important role in regulating cellular division, proliferation, differentiation, and migration and have prognostic significance in a number of cancers. Here, we sought to define their role in extrahepatic cholangiocarcinoma (EHCC). HER2 and HER3 protein expression was studied in 230 EHCC cases using a tissue microarray and compared with clinicopathological variables, including the survival of EHCC patients. HER3 was predominantly localized to the cytoplasm, whereas HER2 exhibited a membranous expression pattern. Overexpression of HER2 and HER3 was observed in 6?% (13/224) and 39?% (90/230) of EHCCs, respectively. Membranous HER2 overexpression occurred more frequently in intraductal papillary neoplasms with an associated invasive carcinoma than in tubular adenocarcinomas (P?=?0.02). HER3 protein was more commonly overexpressed in nodular and infiltrative than in papillary tumors (P?=?0.03). HER3 overexpression was associated with decreased survival in both univariate (P?=?0.01) and multivariate (P?=?0.008) analyses, whereas HER2 overexpression was not associated with survival. HER2 and HER3 are overexpressed in subsets of EHCC patients. Notably, HER3 overexpression is correlated with decreased patient survival, suggesting that HER3 constitutes a prognostic factor as well as a potential candidate for targeted therapy.     

Low PBRM1 identifies tumor progression and poor prognosis in breast cancer

Background: To investigate the expression and role of PBRM1 in breast cancer, and to evaluate the clinical and prognostic significance of PBRM1 protein in patients with breast cancer. Methods: The expression of PBRM1 was examined in breast cancer tissue and paired non-cancerous tissues by real-time PCR. Moreover, PBRM1 protein expression was evaluated by immunohistochemistry in 150 paraffin-embedded breast cancer specimens. The correlation between PBRM1 expression and clinicopathological features were statistically analyzed. Results: The status of PBRM1 protein in breast cancer tissues is much lower than that in paracarcinoma tissues. Low PBRM1 expression was positively correlated with tumor stage (P =0.003) and lymph node metastasis (P =0.013). The overall (P =0.003) and recurrent-free survival (P =0.001) of the patients with high PBRM1 expression was significantly lower than the low PBRM1 expression group. Multivariate analysis showed that the expression of PBRM1 was an independent factor of overall survival for the patients with breast cancer (P =0.030). Conclusions: PBRM1 might involve in the development and progression of breast cancer as a tumor suppressor, and thereby may be a valuable prognostic marker for breast cancer patients.     

Decreased expression of TFPI-2 correlated with increased expression of CD133 in cholangiocarcinoma

Background: Recent findings suggest decreasing TFPI-2 expression plays a significant role in inhibiting cell migration and tumor invasion. The clinicopathological significance of the expression of TFPI-2 and its possible correlation with the expression of CD133 in cholangiocarcinoma remains to be solved. Methods: We investigated if TFPI-2 was involved in the clinicopathological significance of cholangiocarcinoma. An immunohistochemical method was used to detect 218 cases of cholangiocarcinoma, 30 para-neoplastic and 20 normal bile ducts for their expression status of TFPI-2 and CD133, and then the results were analyzed with the patient’s age, sex, tumor site and the histological grade, clinical stage as well as overall mean survival time. Results: Compared with the para-neoplastic and normal cholangiocytes, the expression of TFPI-2 was obviously decreased while the expression of CD133 in carcinoma cells was increased. Carcinomas with low expression of TFPI-2 were significantly corresponding to the tumor site (P = 0.006), size (P = 0.005), histological grade (P = 0.0001) and clinical stage (P = 0.0001), but not to the age (P = 0.066) and sex (P = 0.411), respectively. By Kaplan-Meier survival analysis, the low expression of TFPI-2 was significantly correlative with the overall survival time (P = 0.0001). Further, the expression of TFPI-2 was found inversely correlative with the expression of CD133 (g = -0.3876, P < 0.0001). Conclusions: Our finding suggests that the decreased expression of TFPI-2 may play an important role in the carcinogenesis and progression, and may become a new adjunct marker in the diagnosis and prognosis in cholangiocarcinoma. The expression of TFPI-2 may be inversely correlative with the expression of CD133.     

Expression of ITGB1 predicts prognosis in colorectal cancer: a large prospective study based on tissue microarray

Background: ITGB1 is a heterodimeric cell-surface receptor involved in cell functions such as proliferation, migration, invasion and survival. The aim of this study was to assess ITGB1 expression in colorectal cancer and correlate it with clinicopathological features, as well as to evaluate its potential prognostic significance. Materials and methods: In this study, we examined the expression of ITGB1 using tissue microarrays containing analyzed specimens by immunohistochemistry. ITGB1 expression was further correlated with clinicopathological and prognostic data. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. A multivariate study with the Cox’s proportional hazard model was used to evaluate the prognostic aspects. Results: ITGB1 expression was present in 88.5% of the analyzed specimens. Significant differences in ITGB1 expression were found between normal mucosa and carcinomas (P<0.001). High ITGB1 expression was associated with poor prognosis, and it independently correlated with shortened overall survival and disease-free survival in colorectal cancer patients (P<0.001). More so, ITGB1 expression, bowel wall invasion, lymph node metastasis and distant metastasis were independent prognostic factors for overall survival. Additionally, significant differences in ITGB1 expression were observed in adenomas and tumors from patients with familial adenomatous polyposis compared to normal colon mucosa (P<0.05) Conclusion: The results of this study indicate that ITGB1 overexpression in colorectal tumors is associated with poor prognosis, as well as aggressive clinicopathological features. Therefore, ITGB1 expression could be used as potential prognostic predictor in colorectal cancer patients.