Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal carcinoma

Luo W‐R, Wu A‐B, Fang W‐Y, Li S‐Y & Yao K‐T (2012) Histopathology  61, 237–246 Nuclear expression of N‐cadherin correlates with poor prognosis of nasopharyngeal carcinoma Aims: To investigate the aberrant expression of N‐cadherin in nasopharyngeal carcinoma (NPC) and its prognostic significance. Methods and results: Immunohistochemical staining for N‐cadherin protein was performed on tissue microarray (TMA) from 122 NPC patients. Cytoplasmic N‐cadherin was observed in 42.6% and nuclear N‐cadherin in 45.1% of NPC tissues. High expression of cytoplasmic and nuclear N‐cadherin was associated with a majority of the clinicopathological variables, including lymph node metastasis, distant metastasis and clinical stage. Cytoplasmic N‐cadherin was associated positively with nuclear N‐cadherin expression (P = 0.000). In univariate analysis, cytoplasmic N‐cadherin showed no significant impact on patient prognosis. In contrast, the overall survival was significantly shorter in patients with high nuclear N‐cadherin than those with low levels of staining (P = 0.002). A high expression of nuclear N‐cadherin predicted poorer survival in patients with late stage disease (P = 0.033), but not those with early tumour stage. In addition, multivariate analysis showed nuclear N‐cadherin to bean independent prognostic marker for NPC patients (P = 0.024). Conclusions: Nuclear N‐cadherin expression may represent a valuable prognostic marker in NPC patients, especially those with late stage disease.     

Tumour budding and the expression of cancer stem cell marker aldehyde dehydrogenase 1 in nasopharyngeal carcinoma

Luo W‐R, Gao F, Li S‐Y & Yao K‐T
(2012) Histopathology
Tumour budding and the expression of cancer stem cell marker aldehyde dehydrogenase 1 in nasopharyngeal carcinoma Aims: To detect the prognostic significance of tumour budding and its expression of aldehyde dehydrogenase 1 (ALDH1) in nasopharyngeal carcinoma (NPC). Methods and results: Tumour budding was investigated in 105 patients with NPC by immunohistochemistry for pan‐cytokeratin (AE1/AE3). The intensity of budding correlated strongly with T classification (P = 0.008), lymphatic invasion (P < 0.001), vascular invasion (P = 0.029), lymph node metastasis (P < 0.001), and clinical stage (P = 0.010). Univariate analysis revealed that patients with high budding grade had poorer survival than those with low grade (P = 0.002). Multivariate analysis showed that tumour budding was an independent predictor of survival (P = 0.001). Furthermore, budding cells showed high‐level expression of the cancer stem cell (CSC) marker ALDH1. Budding cells with high‐level ALDH1 expression contributed to several aggressive behaviours and poor survival (P = 0.000). Conclusions: We describe, for the first time, the presence of tumour budding and its correlation with aggressive tumour behaviour and poor patient survival in NPC. The degree of tumour budding could be a valuable predictive factor in NPC. In addition, we show, also for the first time, that budding cells in NPC might possess the invasive and metastatic properties of CSCs.     

Clinical and biological significance of hepatoma‐derived growth factor in Ewing's sarcoma

We sought to investigate the clinicopathological significance and biological function of hepatoma‐derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up‐regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p < 0.001), metastases at diagnosis (p < 0.001), low overall survival rate (p < 0.001) and low disease‐free survival rate (p < 0.001). HDGF knock‐down results in significant reduction of Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock‐down causes cell cycle arrest and enhanced sensitization to serum starvation‐induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety‐eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock‐down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Neoplastic spindle cells in nasopharyngeal carcinoma show features of epithelial-mesenchymal transition

Luo W‐R, Chen X‐Y, Li S‐Y, Wu A‐B & Yao K‐T
(2012) Histopathology  61, 113–122 Neoplastic spindle cells in nasopharyngeal carcinoma show features of epithelial–mesenchymal transition Aim: To investigate whether the neoplastic spindle cells in nasopharyngeal carcinoma (NPC) are associated with the process of epithelial–mesenchymal transition (EMT). Methods and results: We used immunohistochemistry to analyse the expression of cytokeratin, E‐cadherin, β‐catenin, vimentin, fibronectin, Snail1, Slug and aldehyde dehydrogenase 1 (ALDH1) in 115 cases of NPC in which there were neoplastic spindle cells; in 47 cases a neoplastic squamous cell component was also present. There was no significant difference in the expression of cytokeratin observed in the neoplastic spindle cells (P = 0.644), compared to the squamous component whereas E‐cadherin expression was reduced. By contrast, the expression of β‐catenin, vimentin, fibronectin, Snail1, Slug and ALDH1 was up‐regulated in the spindle cells (all P = 0.000). Furthermore, E‐cadherin expression was associated negatively with β‐catenin (P < 0.001), vimentin (P < 0.001), fibronectin (P < 0.001), Slug (P < 0.001) and ALDH1 (P < 0.001) in neoplastic spindle cells, but did not correlate with Snail1 expression (P =0.093). Conclusions: Our findings demonstrate for the first time that EMT might play an important role in the development of neoplastic spindle cells in NPC.     

Survivin and laryngeal carcinoma prognosis: nuclear localization and expression of splice variants

Marioni G, Agostini M, Bedin C, Blandamura S, Stellini E, Favero G, Lionello M, Giacomelli L, Burti S, D’Angelo E, Nitti D, Staffieri A & De Filippis C
(2012) Histopathology  61, 247–256 Survivin and laryngeal carcinoma prognosis: nuclear localization and expression of splice variants Aims: Aberrant survivin expression in cancer cells has been associated with tumour progression, radiation/drug resistance and shorter patient survival. The aim of the present study was to investigate survivin expression in laryngeal carcinoma (LSCC) tissue and – for the first time at this site – the expression of survivin splice variants. P53 was also studied. Methods and results: Survivin and p53 expression was determined immunohistochemically in 86 consecutive patients operated for LSCC. Survivin mRNA expression was assessed by quantitative real‐time polymerase chain reaction (PCR). Hot‐spot mutations in exons 5, 6, 7 and 8 of the TP53 gene were studied by sequencing analysis. A nuclear localization for survivin predominated. There was a significant association between a higher nuclear survivin expression and LSCC recurrence (P = 0.046). Disease‐free survival (DFS) for LSCC patients with a nuclear survivin expression >7.0% was shorter than in cases whose expression was ≤7.0% (P = 0.05). Wild‐type survivin correlated significantly with nuclear survivin expression (P = 0.02). p53 expression was associated with the co‐expression of wild‐type survivin and survivin‐2B (P = 0.01). Conclusions: Nuclear expression of survivin appears to influence LSCC aggressiveness, a higher nuclear survivin expression correlating with a higher recurrence rate and a shorter DFS. Wild‐type survivin was the most frequently detected splice variant in LSCC tissues.     

鼻咽癌组织中c-IAP2的表达及其临床意义

目的 探究细胞凋亡抑制蛋白2(cellular inhibitor of apoptosis protein 2,c-IAP2)在鼻咽癌组织中的表达以及临床意义.方法 回顾性分析95例鼻咽癌患者的肿瘤组织和40例正常患者的鼻咽组织及临床预后资料,分别利用RT-PCR、Western印迹以及免疫组织化学染色检测上述组织中...     

Nuclear p27 Expression Confers a Favorable Outcome for Nasopharyngeal Carcinoma Patients

Objective. The purpose of the present study is to explore the correlation between nuclear expression of cyclin-dependent kinase inhibitor 1B (p27) and clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient survival. Methods. Immunohistochemistry was used to examine the expression of p27 in 130 primary NPC tissues. The relationship between the levels of p27 expression and clinicopathologic characteristics was analyzed. Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. The significance of various survival variables was analyzed using multivariate Cox proportional hazards model. Results. p27 was expressed in both nuclear and cytoplasmic compartments. Nuclear expression of p27 was inversely correlated with T classification and clinical stage. Patients with nuclear p27 expression had better overall survival rates than those without nuclear expression of p27. Further, we observed that nuclear expression of p27 was positively associated with survival time of NPC patients not only in N0-1 and M0 classifications but also in radiotherapy and chemotherapy treatment groups. Finally, we found that nuclear expression of p27 was not an independent prognostic factor for patients with NPC. Conclusions. Our findings hint that nuclear expression of p27 is a potentially favorable factor in the progression and prognosis of NPC.     

Cytoplasmic expression of oestrogen receptor beta (ERβ) as a prognostic factor in vulvar squamous cell carcinoma in elderly women

Zannoni G F, Prisco M G, Vellone V G, De Stefano I, Vizzielli G, Tortorella L, Fagotti A, Scambia G & Gallo D
(2011) Histopathology   59 , 909–917 Cytoplasmic expression of oestrogen receptor beta (ERβ) as a prognostic factor in vulvar squamous cell carcinoma in elderly women Aims: To investigate the prognostic value of cytoplasmic oestrogen receptor beta (ERβ) expression in a series of untreated patients with non‐human papillomavirus (HPV)‐related vulvar cancer. Methods and results: Immunohistochemistry was carried out using a polyclonal rabbit anti‐human ERβ antibody. The nuclear and cytoplasmic expression of ERβ was evaluated in 33 patients. Cytoplasmic immunoreactivity was correlated with histopathological and molecular parameters (Ki67, p21), disease‐free survival (DFS) and overall survival (OS). The expression of cytoplasmic ERβ was found to be associated with grade (P = 0.006), while no association was found with any of the remaining variables examined. Cases with high cytoplasmic ERβ expression showed lower DFS and OS compared to cases with low cytoplasmic ERβ (P = 0.007, P = 0.01, respectively). There was also a progressive decline in both the DFS and OS with increasing tumour size (P = 0.05, P = 0.07, respectively) and with increasing depth of infiltration (P = 0.14, P = 0.07, respectively). On multivariate analysis, only tumour size and cytoplasmic ERβ staining retained an independent negative prognostic role for DFS and OS. Conclusions: The assessment of cytoplasmic ERβ expression could be helpful to identify poor prognosis in elderly patients with non‐HPV‐related vulvar squamous cell carcinoma (SCC).     

Aurora B kinase expression in laryngeal squamous cell carcinoma and its prognostic implications

García‐Fernández E, De Diego J I, Collantes‐Bellido E, Mendiola M, Prim M P, Pérez‐Fernández E, Miguel‐Martín M, Nistal M & Hardisson D
(2011) Histopathology 58 , 368–376
Aurora B kinase expression in laryngeal squamous cell carcinoma and its prognostic implications Aims: To investigate the clinical and prognostic significance of Aurora B in laryngeal squamous cell carcinomas (LSCC). Methods and results: Aurora B protein expression was analysed in 259 LSCC. The proliferation index (Ki67) and the expression of other cell cycle control proteins, such as Aurora A, survivin and p53 was also determined. Aurora B was highly expressed in 55.4% of LSCC. High Aurora B expression levels were correlated with tumour recurrence (P = 0.01), death from disease (P = 0.05) and decreased disease‐free survival (P = 0.013) and overall survival (P = 0.04). Survivin expression was neither associated with clinicopathological characteristics nor with survival. However, survivin expression in the nucleus paralleled Aurora B expression (P = 0.014). Aurora A expression was associated significantly with increased tumour grade (P = 0.008). Multivariate analysis indicated that Aurora B was an independent predictor for LSCC‐specific disease‐free survival [hazard ratio (HR), 2.10; 95% confidence interval (95% CI), 1.25–3.52 (P = 0.005)] and overall survival [HR, 1.91; 95% CI 1.01–3.34 (P = 0.023)]. Conclusions: Aurora B may be a novel prognostic biomarker for LSCC and a potential therapeutic target in this type of tumour.     

Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer

Stenner M, Weinell A, Ponert T, Hardt A, Hahn M, Preuss S F, Guntinas‐Lichius O & Klussmann J P
(2010) Histopathology 57 , 699–706
Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer Aims: The expression of the inhibitor of apoptosis protein survivin has been shown to be a significant prognostic indicator in various human cancers. The aim was to assess its expression and prognostic value in salivary gland adenocarcinoma and muco‐epidermoid carcinoma. Methods and results: Survivin expression was analysed in 48 patients with parotid gland cancer (21 muco‐epidermoid, 27 adenocarcinomas) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. A high cytoplasmic expression of survivin was found in 30% of the examined tumours without any significant correlation with the patients’ clinicopathological characteristics (P > 0.05). Within all patients, the estimated overall survival rate of muco‐epidermoid carcinomas was significantly better than that of adenocarcinomas (P = 0.013). A high cytoplasmic survivin expression significantly indicated a poor 5‐year disease‐free survival rate compared to patients with a low cytoplasmic survivin expression in the whole group (P = 0.001) and in adenocarcinomas (P = 0.004). In a multivariate analysis, a high cytoplasmic survivin expression was the only independent prognostic indicator for a significantly poorer 5‐year disease‐free survival rate (P = 0.001). Conclusions: The correlation between cytoplasmic survivin expression and survival in salivary gland malignancies might make this an effective tool in patient follow‐up, prognosis and targeted therapy in future.     

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

Yoo S H, Lee K, Chae J Y & Moon K C
(2011) Histopathology  58 , 191–197
CD151 expression can predict cancer progression in clear cell renal cell carcinoma Aims: CD151 is known to be implicated in cancer progression and metastasis. The aim was to evaluate the expression of CD151 in clear cell renal cell carcinoma (CCRCC) and to assess its prognostic significance. Methods and results: The expression of CD151 was evaluated in 489 cases of CCRCC by immunohistochemistry. Immunoreactivity was classified into four categories (minimal, 0–10% positive cells; focal, 10–50% positive cells; diffuse moderate, >50% positive cells with moderate staining intensity; diffuse strong, >50% positive cells with strong staining). To determine the statistical significance of CD151 expression in CCRCC, all cases were divided into two groups based on their CD151 expression level: a CD151‐low group (n = 257; minimal and focal) and a CD151‐high group (n = 232; diffuse). Expression of CD151 was correlated positively with pT, pN, pM categories, pathological tumour–node–metastasis (pTNM) stage, nuclear grade, tumour size and patient’s age. The CD151‐high group had significantly shorter cancer‐specific survival (P < 0.001) and progression‐free survival (P < 0.001) times. Furthermore, multivariate analysis showed that CD151 expression was an independent predictor for tumour progression in patients with CCRCC (P = 0.040). Conclusions: High CD151 expression is associated with advanced stage and high nuclear grade in CCRCC. CD151 is a prognostic marker for tumour progression in CCRCC patients.     

Prognostic value of ABCG2 in moderately and poorly differentiated intrahepatic cholangiocarcinoma

Larbcharoensub N, Sornmayura P, Sirachainan E, Wilasrusmee C, Wanmoung H & Janvilisri T
(2011) Histopathology 59 , 235–246 Prognostic value of ABCG2 in moderately and poorly differentiated intrahepatic cholangiocarcinoma Aims: Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy derived from cholangiocytes. The survival rate of ICC patients is very low, and conventional chemotherapy is not effective in prolonging long‐term survival. Adenosine 5′‐triphosphate (ATP)‐binding cassette (ABC) transporters mediate the transport of various substances in several cellular processes. The expression of ABCB1, ABCC1 and ABCG2 has been implicated in multidrug resistance and poor prognosis in several types of cancer. The aim of this study was to examine their expression in normal cholangiocytes and ICC tissues. Methods and results: Immunohistochemistry was employed to evaluate the expression of these transporters in 60 cases of ICC with respect to clinicopathological features and patient outcome. The proportions of cases with loss of ABCB1, ABCC1 and ABCG2 expression were 93.3%, 68.3% and 50%, respectively. Only the loss of ABCG2 was related to a worse prognosis (P = 0.031), and was associated with lymph node involvement (P = 0.003) and higher tumour grade (P = 0.028). Furthermore, multivariate analysis showed that the loss of ABCG2 expression was an independent prognostic factor in patients with moderately or poorly differentiated ICC (P = 0.02). Conclusions: These results suggest that ABCG2 may be involved in cholangiocarcinogenesis; the loss of its expression may enhance tumour progression and contribute to aggressive growth of ICC.     

The influence of transforming growth factor-α, cyclooxygenase-2, matrix metalloproteinase (MMP)-7, MMP-9 and CXCR4 proteins involved in epithelial-mesenchymal transition on overall survival of patients with gastric cancer

Fanelli M F, Chinen L T D, Begnami M D, Costa W L Jr, Fregnami J H T, Soares F A & Montagnini A L
(2012) Histopathology  61, 153–161 The influence of transforming growth factor‐α, cyclooxygenase‐2, matrix metalloproteinase (MMP)‐7, MMP‐9 and CXCR4 proteins involved in epithelial–mesenchymal transition on overall survival of patients with gastric cancer Aims: Determination of prognostic parameters that are predictive of survival of gastric cancer (GC) may allow better identification of patients who could benefit from current chemotherapy regimens. To assess the correlation between tumour progression and epithelial–mesenchymal transition (EMT), we assayed the expression levels of selected molecules involved in EMT [CD44, transforming growth factor (TGF)‐α, cyclooxygenase‐2 (COX‐2), matrix metalloproteinase (MMP)‐7, MMP‐9 and C‐X‐C chemokine receptor (CXCR4)], and correlated these with overall patient survival (OS) and disease stage. Methods and results: Medical records and pathological biopsy results of 137 patients with GC were evaluated retrospectively. Spearman’s correlation analysis showed that expression of CXCR4 was correlated significantly with the expression of all other proteins studied. In contrast, COX‐2 expression correlated significantly with the expression of only MMP‐7 (P = 0.011), MMP‐9 (P = 0.015) and CXCR4 (P = 0.013). We observed significant negative correlations between OS and the expression of TGF‐α (P = 0.017), COX‐2 (P < 0.001), CXCR4 (P = 0.010), MMP‐7 (P = 0.020) and MMP‐9 (P = 0.015). On multivariate analysis, only COX‐2 was an independent prognostic factor for OS [hazard ratio (HR) = 3.34; 95% confidence interval (CI): 1.43–9.75; P = 0.002). Conclusions: COX‐2, TGF‐α, MMP‐7, MMP‐9 and CXCR4 are associated with poor OS in gastric cancer.     

Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III-IV serous ovarian carcinoma

Li C, Li Y, Wang X, Wang Z, Cai J, Wang L, Zhao Y, Song H, Meng X, Ning X, Xu C, Lin M, Li L & Geng J
(2012) Histopathology  60, 953–963 Elevated expression of astrocyte elevated gene‐1 (AEG‐1) is correlated with cisplatin‐based chemoresistance and shortened outcome in patients with stages III–IV serous ovarian carcinoma Aims: To correlate astrocyte elevated gene‐1 (AEG‐1) expression with the clinicopathological features and outcome of patients with stages III–IV ovarian serous carcinoma, and to clinically assess the involvement of AEG‐1 in acquired cisplatin resistance. Methods and results: The frequency and intensity of immunohistochemical AEG‐1 expression increased in a step‐wise fashion from normal to chemosensitive to chemoresistant tissues. These observations were confirmed by Western blot analysis. AEG‐1 expression level was correlated with lymph nodal metastasis, histological differentiation, residual tumour size and response to primary chemotherapy. Five‐year progression‐free survival (PFS) and overall survival (OS) rates were lower in the high‐expression group than that in the low‐expression group. AEG‐1 overexpression was an independent but poor prognostic factor in the OS and PFS of these patients, as determined by multivariate Cox regression analysis. Multivariate logistic regression analysis revealed that the presence of cisplatin‐based chemoresistance was significantly associated with expression level of AEG‐1 and the degree of residual disease (P = 0.0001 and P = 0.0027, respectively). Conclusion: Our findings indicate that tumour AEG‐1 overexpression is associated with poor prognosis and cisplatin resistance in advanced serous ovarian cancer.     

Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma

Huang C, Sun Z, Sun Y, Chen X, Zhu X, Fan C, Liu B, Zhao Y & Zhang W
(2012) Histopathology  60, 793–803 Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma Aims: We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC). Methods and results: We studied the expression of CypA, CD147, hypoxia‐inducible factor 1α (HIF‐1α), vascular endothelial growth factor A and C (VEGF‐A and VEGF‐C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF‐1α, VEGF‐A and VEGF‐C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P < 0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF‐1α, VEGF‐A and VEGF‐C. A significant relationship between VEGF‐A and VEGF‐C was also detected (P < 0.01). Patients with overexpression of CypA, CD147, HIF‐1α and VEGF‐C had significantly worse overall survival (P < 0.05) using Kaplan–Meier analysis. Multivariate Cox regression analysis showed that HIF‐1α, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients. Conclusions: The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.     

High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma

Scattone A, Serio G, Marzullo A, Nazzaro P, Corsi F, Cocca M P, Mattoni M, Punzi A, Gentile M, Buonadonna A L & Pennella A
(2012) Histopathology 60, 472–481
High Wilms’ tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma Aims: To evaluate the use of the Wilms’ tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM). Methods and results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High‐grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high‐power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05–3.71] versus 31.5 months (95% CI: 20.4–42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively). Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.     

Prognostic value of nuclear hepatoma-derived growth factor (HDGF) localization in patients with breast cancer

Hepatoma-derived growth factor (HDGF) plays an important role in tumor progression. Highly expressed HDGF has been found to indicate poor prognosis in many cancers. However, no information is available regarding the prognostic value of nuclear or cytoplasmic HDGF staining level in breast cancer. In the present study, the nuclear or cytoplasmic HDGF staining level was investigated in 86 patients with primary breast cancer by immunohistochemistry; the relationship between nuclear or cytoplasmic HDGF staining level and clinicopathological parameters was examined by Two-tailed Mann-Whitney U-test or Krustal-Wallis. The prognostic value of nuclear or cytoplasmic HDGF staining level in disease-free survival and overall survival was analyzed by Kaplan-Meier methods and log-rank test. We found that the percentage of cases with strong nuclear HDGF staining level was significantly higher in the cases with high tumor grade, high stage, high proliferation index (Ki-67 index>20%), as well as in those with lymph node invasion and recurrence (p<0.05) compared to those without. No significant correlation was found between cytoplasmic HDGF expression and any clinicopathological variables. In addition, disease-free survival and overall survival were significantly lower in patients with high nuclear HDGF expression (level 2) than in those with low nuclear HDGF expression (level 0 and level 1). Further Cox multivariate analysis showed that high nuclear HDGF expression is an independent factor for indicating poor prognosis in breast cancer patients. No significant difference in disease-free survival rate and overall survival was found between different cytoplasmic HDGF staining levels. All these findings suggest that increased nuclear HDGF expression is involved in tumor progression and might be used as a new prognosticator for breast cancer.