Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma

Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors.However,prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC).To clarify whether the level of serum enzymes is linked to the prognosis of NPC,we reviewed the pretreatment data of lactate dehydrogenase(LDH),alkaline phosphatase (ALP),and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center.Patients were grouped according to the upper limit of normal values of LDH,ALP,and GGT.The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes,and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes.Finally,a Cox proportional hazards model was used to identify the independent prognostic factors.We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival(P=0.009 and 0.035,respectively),and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival(P=0.037 and 0.039,respectively).In multivariate analysis,increased LDH level was identified as an independent prognostic factor for overall survival.Therefore,we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.     

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Objective:To investigate the expression level of serum vascular endothelial growth factor(VEGF) in patients with unresectable hepatocellular carcinoma(HCC) and its relationship with the clinicopathological characteristics,and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization(TACE) treatments.Methods:Serum VEGF levels were measured using enzyme-linked immunosorbent assay(ELISA) in 60 random patients who underwent TACE or transarterial infusion(TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control.All patients’ clinicopathological features were retrospectively analyzed.Serum VEGF levels were correlated with clinicopathological features of the HCC patients.The patients’ survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test.The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.Results:The median serum VEGF level in the HCC patients was 285 pg/ml(range 14 1,207 pg/ml),significantly higher than that of healthy controls(P=0.021).The serum VEGF levels were significantly correlated with platelet counts(r=0.396,P=0.002) but not other clinicopathological features.Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml(P=0.002).By multivariate analysis,the serum VEGF level was a significant prognostic factor.Conclusion: High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.     

肥胖乳腺癌患者的临床特征及预后的回顾性研究(英文)

Objective:The aim of our study was to investigate the prognosis of obese breast cancer patients.Methods:This study was conducted on a total of 317 breast cancer patients who were histopathologically and clinically diagnosed at the General Hospital of Shenyang Military Region(China)from 2004 to 2006.Clinical data including height,weight,age at diagnosis,tumor size,lymph node status,menopausal status,family history of cancer and hormone receptor status were collected.Log-rank test was performed to compare the disease free survival(DFS)and overall survival(OS).Cox proportional hazards regression analysis was conducted to make multivariate analysis.The Chi square test was used to compare the clinical features among normal weight group,overweight group,and obese group.Results:Obesity was an independent prognostic factor for DFS(P=0.022)and OS(P=0.032)in breast cancer patients.In the stratified analysis based on the hormone receptor status,obesity was independently associated with OS in patients with negative ER/PR(P=0.002),but such association was not observed in patients with positive hormone receptors.Obesity was also associated with lymph node status(P=0.001)and smoking(P=0.009).Conclusion:Obesity is associated with poor DFS and OS in patients with breast cancer.Therefore,maintaining normal weight may benefit breast cancer patients.     

淋巴结阴性乳腺癌PAI-Ⅰ表达及预后价值

Objective:To investigate the expressions of plasminogen activator inhibitor type 1(PAI-1),C-erbB-2,VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAJ-1 in node-negative breast cancer,Methods:The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cencer.Expressions of PAI-1,C-erbB-2,VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months(range 22-117 months).Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed.Results:High PAI-1 level was positively associated with high histologic grade of the tumors.Disease-free survival(DFS)was significantly shorter for the patients with moderate to intensive expression of PAI-1 lban for those with negative(X2=25.46,P＜0.001:X2=23.07,P＜0.001)to mild expression(X2=19.75,P＜0.001:X2=17.40.P＜0.001).Although on univariate analysis of the prognostic factors,tumor size,location of primary tumor and age as well as expressions of PAI-1,VEGF and Ki-67 were all significantly prognostic factors for DFS(P＜0.05),PAI-1 was the only independent prognostic factor on multivariate analysis(P＜0.0001;hazard ratio[HR].4.041:95% confidence intewal[CI],1.928-8.468).Conclusion:These results of the current study indicate that intermediate or high expression of PAI-1 represents a strong and independent unfavorable prognostic factor for the development of recurrence or metastases in axillary node-negative breast cancer.     

Glasgow prognostic score after concurrent chemoradiotherapy is a prognostic factor in advanced head and neck cancer

Objective:This study aims to evaluate the impact and potential prognostic roles of the pre-and post-treatment Glasgow prognostic score (GPS) and the change thereof in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy (CCRT).Methods:We collected GPS and clinicopathological data of 139 stage Ⅲ,ⅣA,and ⅣB head and neck cancer patients who underwent CCRT between 2008 and 2011.Their GPSs pre-and post-CCRT and the change thereof were analyzed for correlations with recurrence and survival.Results:The GPS changed in 72 (51.8％) patients,with worse scores observed post-CCRT in 65 (90.3％) of the GPS changed patients.Patients in the improved GPS group showed a tendency toward better survival.From the multivariate analysis,the post-CCRT GPS level was an independent prognostic factor in addition to tumor stage.Conclusions:After CCRT,a high GPS was revealed to be an important predictor of survival for advanced head and neck cancer.     

Over-expression of metastasis-associated in colon cancer-1 (MACC1) associates with better prognosis of gastric cancer patients

Objective: The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods: The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results: The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression. Conclusion: MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.     

Expression of heparanase and its clinical significance in human non-small cell lung cancer

Objective： To explore the expression and significance of heparanase in non-small cell lung cancer （NSCLC） regarding prognosis and clinicopathological parameters. Methods： The expression of heparanase was assessed using immunohistochemistry staining and Western blot in 122 paraffin-embedded specimens and 38 freshly taken tissues. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi-square test, multivariate analysis and Kaplan-Meier method. Results： In the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissue （78.7%, 96/122） while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissue （P=0.043）. Expression of heparanase significantly correlated with TNM stage （P=0.025）, lymphatic metastasis （P=0.002） and vascular invasion （P=0.0003）. The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression （P=0.0006）. In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors. Conclusion： Elevated level of heparanase in human non-small cell lung cancer tissues correlates with the TNM stage, invasion, metastasis and prognosis. However, heparanase expression is not an independent prognostic factor.     

胃癌组织中Ets-1的表达及其与血管生成临床病理特征和预后的关系

Objective To investigate the expression of Ets-I in gastric carcinoma,pars-cancerous tissue and metastatic lymph nodes,and to determine the relationship between Ets-1 expression and clinicopathological features,angiogenesis and survival of patients with gastric carcinoma.Methods Gastric carcinoma tissue microarray was used to determine Ets-I protein expression by SP immunohistochemical staining in 189 advanced gastric cancer,54 papacancerous tissues,41 metastatic lymph nodes and 32 control tissues.Results The positive rates for Ets-1 expression of the carcinoma,paracancerous and control tissues were 71.4 %,29.6% and 18.8%,respectively,with a significant difference among the three groups(P ＜0.01).In the cancer tissues,the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis(P ＜0.01),but not associated with degree of differentiation,Lauren's histological type,sex,age,and size of tumor(P ＞0.05).The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different(P ＜0.05).In metastatic lymph nodes,the positive rate for Ets-1 expression was higher.The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors,with a significant difference(P ＜ 0.05).Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P ＜0.05).Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma.Conclusion A higher expression of Ets-1 is involved in carcinogenesis,development,invasion,and metastasis of gastric cancer.Ets-1 plays an important role in angiogenesis in gastric cancer.Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma,though it is not an independent prognostic indicator.     

血清白细胞介素18在前列腺癌患者中的临床价值

Objective: To determine serum interleukin-18 (IL-18) levels and their clinical significance in patients with prostate cancer. Methods: Peripheral blood samples were obtained from 38 nonmetastatic and 18 metastatic prostate cancer patients who underwent curative surgery and from 25 healthy volunteers. The serum IL-18 level was determined in each sample with the enzyme-linked immunosorbent assay. Results: The levels of serum IL-18 were increased significantly in prostate cancer patients compared with control subjects (P ＜ 0.05). Serum IL-18 levels were significantly higher in the metastatic patients compared with the nonmetastatic patients (P ＜ 0.01). Patients with bone metastasis had higher serum IL-18 levels compared with patients with liver and lung metastasis (P ＜ 0.01). When the patients were subdivided into groups, it was found that the serum IL-18 levels in patients with T2, T3 and T4 stage were significantly higher than that of T1 stage patients (P ＜ 0.01). Patients with IL-18 levels ≥ 316 pg/mL experienced a significantly lower survival rate compared with the patients who had IL-18levels ＜ 316 pg/mL after undergoing surgery (P ＜ 0.05). The serum IL-18 level was identified as an independent postoperative prognostic factor in multivariate survival analysis using a Cox proportional hazards model (hazard ratio, 4.21; P = 0.02).Conclusion: The serum IL-18 level may be a useful marker in monitoring prostate cancer patients. IL-18 activity in prostate cancer patients with bone metastasis may be more valuable in the follow-up.     

DBC1 is over-expressed and associated with poor prognosis in colorectal cancer

Background

Deleted in breast cancer 1 (DBC1) was initially cloned from a region homozygously deleted in breast cancers, but its role in colorectal cancer remains unknown. The present study aims to examine the expression level of DBC1 and assess its prognostic value in human colorectal cancer.

Methods

Immunohistochemical staining was performed to detect the expression level of DBC1 in a series of 186 colorectal cancer patients. Immunohistochemical staining results were analyzed and compared statistically with various clinicopathological characters and overall survival.

Results

Compared with the corresponding non-tumor tissues, a higher expression level of DBC1 was detected in colorectal cancer (P < 0.01). Tissue microarray analysis revealed that DBC1 expression is significantly associated with tumor histological grade, TNM stage and metastatic status (P < 0.01). Importantly, Kaplan–Meier analysis showed that DBC1 expression is associated with shorter overall survival (P < 0.01). Univariate Cox regression suggested that DBC1 expression, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival in colorectal cancer (P < 0.05). Multivariate Cox regression analysis indicated that DBC1 acts as an independent prognostic factor in colorectal cancer (P < 0.01).

Conclusions

These results suggest that DBC1 is over-expressed in colorectal cancer and that it might serve as a predictor for selecting patients at high risk of poor prognosis.     

Clinical characteristics and outcomes for gastric cancer patients aged 18–30 years

Background

There is little known about the clinicopathological features and the predictors of survival in extremely young adult patients aged 18–30 years. The aim of this study was to identify clinicopathological features and clinical outcomes for the overall population and for a resectable subgroup of gastric cancer patients aged 18–30 years.

Methods

From January 2004 to December 2010, 207 patients aged between 18 and 30 years old were diagnosed with gastric cancer and treated at the Asan Medical Center. Clinical findings, histopathological parameters and outcomes were reviewed retrospectively. Patients were further divided into 2 groups according to tumor resectability and then clinicopathological factors that affect tumor resectability and clinical outcomes were analyzed.

Results

Clinicopathological characteristics of study population showed a predominance of females, undifferentiated tumors, diffuse-type cancers, and advanced gastric cancer. The overall resectability rate was 70.0 % and the median follow-up period was significantly longer in the resectable tumor group (P < 0.001). Significant prognostic predictors for overall survival in overall patients were higher CEA levels (P = 0.016), larger tumor size (P < 0.001), unresectability (P = 0.006), and presence of lymphovascular invasion (P = 0.012) in a multivariate analysis. Significant prognostic factors for overall survival in patients with resectable disease included larger tumor size (>4 cm), lymphovascular invasion and higher CEA level in the multivariate analysis.

Conclusions

Gastric adenocarcinomas in young adult patients aged 18–30 years have unique clinicopathological features. Early detection in a resectable state and subsequent complete resection could increase survival period in young patients with gastric cancer.     

Clinical importance of phosphatase of regenerating liver-3 expression in breast cancer

Background

Several biomarkers have been previously studied for breast cancer to define risk of recurrence and metastasis. Phosphatase of regenerating liver-3 (PRL-3) is one of them. High PRL-3 expression has been found to be correlated with axillary lymph node metastasis and survival in breast cancer. Herein, we evaluated the prognostic significance of PRL-3 expression and the relationship between PRL-3 and other clinicopathological factors.

Methods

PRL-3 expression was analyzed immunohistochemically in 122 invasive breast cancer tissues. We evaluated the correlation between PRL-3 and other clinicopathological factors by ??2 test. Kaplan?CMeier test and log rank method were used to define prognostic importance of PRL-3 expression.

Results

Of 122 breast cancer tumor samples, 46 (37.7?%) were negative while 76 (62.3?%) were positive in respect to PRL-3 expression. There was significant correlation between PRL-3 expression and other clinicopathological factors, such as histology, lymphovascular invasion (LVI), necrosis, progesterone receptor (PR) status, and the presence of triple negative disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared to tumors without LVI or necrosis (P?=?0.05 and 0.03, respectively). Triple negative and cerb-B overexpressed breast cancers were found to be more positive PRL-3 expression than hormone receptor positive with cerb-B negative groups (luminal A) (P?=?0.02).We could not find any relationship between PRL-3 expression and overall survival (OS) or disease-free survival (DFS) (P?>?0.05).

Conclusion

Although PRL-3 expression was related to LVI or necrosis which is important for tumor invasiveness, we could not find that PRL-3 as an important prognostic factor in breast cancer patients. In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group.     

Prognostic significance of NANOG and KLF4 for breast cancer

Background

Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of iPS cell-inducing factors and the prognosis of breast cancer patients.

Methods

In 100 breast cancer patients, the expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 was determined by immunohistochemistry using a tissue microarray analysis.

Results

Patients with strong expression of NANOG had significantly lower disease-free survival (DFS) and overall survival rates than those with weak expression of NANOG (P = 0.004 and 0.033, respectively). In contrast, patients with strong expression of KLF4 had better DFS (P = 0.014).

Conclusions

Strong expression of NANOG is an indicator of a poor prognosis for breast cancer patients, whereas KLF4 is a favorable prognostic indicator. Our results suggest that NANOG stimulates the growth and metastasis of breast cancer cells, whereas KLF4 inhibits these processes.     

A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer

Background:

The detection of circulating tumour cells (CTCs) has been linked with poor prognosis in advanced breast cancer. Relatively few studies have been undertaken to study the clinical relevance of CTCs in early-stage breast cancer.

Methods:

In a prospective study, we evaluated CTCs in the peripheral blood of 82 early-stage breast cancer patients. Control groups consisted of 16 advanced breast cancer patients and 45 healthy volunteers. The CTC detection was performed using ErbB2/EpCAM immunomagnetic tumour cell enrichment followed by multimarker quantitative PCR (QPCR). The CTC status and common clinicopathological factors were correlated to relapse-free, breast cancer-related and overall survival.

Results:

Circulating tumour cells were detected in 16 of 82 (20%) patients with early-stage breast cancer and in 13 out of 16 (81%) with advanced breast cancer. The specificity was 100%. The median follow-up time was 51 months (range: 17–60). The CTC positivity in early-stage breast cancer patients resulted in significantly poorer relapse-free survival (log rank test: P=0.003) and was an independent predictor of relapse-free survival (multivariate hazard ratio=5.13, P=0.006, 95% CI: 1.62–16.31).

Conclusion:

The detection of CTCs in peripheral blood of early-stage breast cancer patients provided prognostic information for relapse-free survival.     

Over-expression of Her-2 in colorectal cancer tissue, but not in serum, constitutes an independent worse prognostic factor

Background

Currently, conflicting information exists regarding Her-2 over-expression and its clinicopathological implications in colorectal cancer (CRC). This study was undertaken to determine Her-2 over-expression in both serum and tumor tissue of CRC patients, and to assess its clinicopathological and targeted therapeutic implications.

Methods

Ninety five CRC patients and sixty healthy controls were prospectively enrolled. Her-2 expression status in serum and CRC tissue were examined by chemiluminescent immunoassay and immunohistochemical staining, respectively. The results were confirmed using fluorescent in situ hybridization. Clinicopathological parameters were analyzed according to Her-2 expression status.

Results

Serum Her-2 levels were found to be increased in CRC patients as compared to those of healthy controls. However, serum Her-2 levels were not found to be significantly associated with prognostic parameters. Her-2 expression analysis of CRC tissues revealed Her-2 over-expression in 23 patients (25%), i.e., 13 patients (14%) showed moderate over-expression and 10 patients (11%) showed strong over-expression. The overall survival of patients negative for Her-2 expression was significantly better than that of patients positive for Her-2 expression (P?=?0.018). The disease-free survival of patients with Her-2 over-expression was significantly shorter than that of patients with no Her-2 expression (P?=?0.021).

Conclusions

Her-2 over-expression in CRC tissue, but not in serum, acts as a significant independent worse prognostic factor. Assessment of Her-2 expression status may be valuable for the targeted therapeutic management of CRC.     

延迟辅助化疗对乳腺癌患者生存期的影响(英文)

Objective: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. It is usually prescribed within 2-3 months after definitive surgery. The aim of this retrospective study was to assess the impact of adjuvant chemotherapy (CT) delay beyond 3 weeks ( 21 days) in premenopausal patients with ER-absent tumors being treated for early stages breast cancer on overall survival (OS) and disease-free survival (DFS). Methods: This retrospective study was conducted through revision of medical records of premenopausal patients diagnosed with early stage Ⅰ-ⅢA breast cancer and ER-absent tumors who received adjuvant CT after definitive surgery at the Department of Clinical Oncology, Ain-Shams University Hospitals. Results: Between 2005 and 2008, 105 patients were retrospectively analyzed and included. Patients were divided into 2 groups: Group A including 48 patients who started adjuvant CT<21 days of surgery and group B which included 57 patients who had CT delay ≥ 21 days. Both groups were matched demographically. Comparisons of overall survival, and disease-free survival between group A and group B patients all favored group A. At 5-year the OS rates were 87% and 73% for groups A and B respectively (P=0.001), while DFS rates were 85% and 64% in groups A and B respectively (P=0.001). Analysis of other prognostic factors (age, T, N, grade, HER2 status, surgery type, CT type, local radiotherapy received) were analyzed. Only nodal status predicted for worse DFS (P=0.05) and OS (P=0.006). Conclusion: Delay in initiating adjuvant chemotherapy for early stage breast cancer patients with ER-absent tumors was associated with a decrease in both OS and DFS rates.     

Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: a cohort study

Introduction

Several in vitro studies have suggested the effects of adipokines and insulin resistance on breast cancer cell proliferation and survival. However, little is known about the clinical significance of these findings.

Methods

We examined associations between breast cancer recurrence and adiponectin, leptin, insulin resistance, and metabolic syndrome (MetS) in a cohort of 747 patients from 2001 to 2004.

Results

Adjusted hazard ratios showed an inverse trend across the quartiles for serum adiponectin concentration in estrogen receptor (ER)/progesterone receptor (PR) -negative patients (P for trend = 0.027) but not in ER/PR-positive patients. Compared to the highest quartile for adiponectin level, the lowest quartile showed a hazard ratio of 2.82 (1.03 to 7.68). Homeostasis model assessment for insulin resistance (HOMA-IR) showed a positive trend for recurrence in the ER/PR-negative group (P for trend = 0.087) and a negative trend in the ER/PR-positive group (P for trend = 0.081). Leptin did not show any associations (P for trend >0.05). A linear trend was observed with the number of components of MetS in ER/PR-negative patients (P for trend = 0.044). This association disappeared when adjusted for adiponectin and HOMA-IR.

Conclusions

Adiponectin and HOMA-IR have prognostic significance in breast cancer recurrence and interventions related to these factors may protect against recurrence in ER/PR-negative patients. These findings were not observed in the case of ER/PR-positive patients. Further evaluation of these insignificant associations is needed because it might be biased by adjuvant chemotherapy or other confounders.