• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.539-543
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• 2016

Background: It is well known that peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is associated with a poor prognosis. However, data on the prognostic significance of modern chemotherapy containing bevacizumab, cetuximab or panitumumab are not available. Materials and Methods: This retrospective review concerned 526 patients with metastatic CRC who were classified into two groups according to the presence or absence of PC, and were treated with systemic chemotherapy, with or without bevacizumab or anti-EGFR antibodies. The genetic background, in particular KRAS, BRAF, and PIK3CA gene mutations, and overall survival (OS) were compared between the two groups. Results: The median OS values were 23.3 and 29.1 months for PC and non-PC patients, respectively (hazard ratio [HR]=1.20; p=0.17). Among all patients, tumor location, number of metastatic sites and BRAF mutation status were significant prognostic factors, whereas the presence of PC was not. In the PC group, chemotherapy with bevacizumab resulted in a significantly longer OS than forchemotherapy without bevacizumab (HR=0.38, p<0.01), but this was not the case in the non-PC group (HR=0.80, p=0.10). Furthermore, the incidence of the BRAF V600E mutation was significantly higher in PC than in non-PC patients (27.7% versus 7.3%, p<0.01). BRAF mutations displayed a strong correlation with shorter OS in non-PC (HR=2.26), but not PC patients (HR=1.04). Conclusions: Systemic chemotherapy, especially when combined with bevacizumab, improved survival in patients with PC from CRC as well as non-PC patients. While BRAF mutation demonstrated a high frequency in PC patients, but it was not associated with prognosis.

• Journal of Gastric Cancer
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• v.2 no.1
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• pp.5-11
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• 2002

Purpose: The purpose of this study is to identify immunohistochemical evidence of lymph-node micrometastasis in histologic node-negative gastric cancer patients and to evaluate the prognostic significance of lymph-node micrometastasis.Materials and Methods: A retrospective study of 50 gastric cancer patients who underwent curative resections from October 1990 to November 1994 was performed. Two consecutive sections were prepared: one for ordinary hematoxylin and eosin staining, and the other for immunohistochemical staining with Pan cytokeratin antibody (Novocastra, UK). In the univariate analysis, the survival rate was calculated using the Life Table Method, and the multivariate analysis was determined using a Cox Proportional HazardsModel. The statistical analyses of the relationships between the clinicopathologic factors and micrometastases were performed by using a Chi-square test. Results: Of 2522 harvested lymph nodes, 81 ($4.1\%$) nodes and 19 ($38\%$) of 50 patients were identified as having lymphnode micrometastases by using immunohistochemical staining for cytokeratin. The incidence of lymph-node micrometastases was significantly higher in diffuse type carcinomas ($54\%$, P=0.024) and in patients with serosal invasion ($52.2\%$, P=0.05). For patients with lymph-node micrometastases (n=19), the 5-year survival rate was significantly decreased ($73.7\%$, P=0.015). The Lauren's classirication (P=0.021) and the depth of invasion (P=0.035) were shown by multivariate analysis to have a significant relationship with the presence of micrometastases. Multivariate analysis revealed that lymph-node micrometastasis was independently correlated with survival in histologic node-negative gastic cancer patients. Conclusion: The presence of cytokeratin detected lymphnode micrometastases correlates with the worse prognosis for patients with histologic node-negative gastric cancer.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.2
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• pp.169-177
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• 2003

Purpose: The purpose of the current study is to evaluate the correlation between the expressions of p21 and p27 in osteosarcoma, and prognostic impact such as local recurrence, distant metastasis and survival rate. Materials and methods: Between 1988 and 2001, forty patients who underwent surgery, followed more than 12 months, and whose pathologic blocks were available, were evaluated retrospectively. Their formalin-fixed and paraffin-embedded tumor specimens were investigated. The correlation between expressions of p21, p27, local recurrence, distant metastasis and survival rate was statistically evaluated. Results: p21 protein was expressed in 38 (95%) patients. p27 protein was expressed in 14 (35%) patients. Patients with high expression of p21 had more frequent metastasis and poorer results (p=0.024). In contrast with these findings, patients with positive staining of the p27 had the significant lower distant metastasis (p=0.028). Conclusion: The prognosis of the osteosarcoma according to the expression level of p21 and p27 had inverse relationship which had unknown mechanism. Further work will be needed to define the relationship between p21 and p27.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7917-7922
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• 2015

DNA ploidy is an important prognostic parameter in paediatric B-ALL, but the significance of the S-phase fraction is unclear. In present study, DNA ploidy was assessed in 40 pediatric B-ALL cases by flow cytometry. The DI (DNA index) and percentage of cells in S-phase were calculated using Modfit software. Aneuploidy was noted in 26/40 (65%) cases. A DI of 1.10-1.6 (hyperdiploidy B) was noted in 20/40 (50%) and 6/40 (15%) had a DI>1.60 (triploid and tetraploid range). Some 14/40 (35%) cases had a diploid DI between 0.90-1.05. None of the cases had a DI <0.90 (hypodiploid) or in the 1.06-1.09 (hyperdiploid A) range. The mean S-phase fraction was 2.6%, with 24/40 (60%) having low and 16/40 (40%) high S-phase fractions. No correlation was noted with standard ALL risk and treatment response factors with DI values or S-phase data, except for a positive correlation of low S-phase with high NCI risk category (p=0.032). Overall frequency of hyperdiploidy in our cohort of B-ALL patients was very high (65%). No correlation between hyperdiploidy B and low TLC or common B-phenotype was observed in our study as 42% cases with DI 1.10-1.6 had TLC> $50{\times}10^9$ and 57.1% CD 10 negativity. The study also highlighted that S-phase fraction analysis does not add any prognostic information and is not a useful parameter for assessment in ALL cases. However, larger studies with long term outcome analysis are needed to derive definitive conclusions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3791-3794
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• 2012

CD44v, especially splice variants containing exon v6, has been shown to be related closely to development of different tumors. High levels of CD44v6/v7 have been reported to be associated with invasiveness and metastasis of many malignancies. The objective of this study was to detect expression of CD44v6-containing variants in patients with acute promyelocytic leukemia (APL) and evaluate the potential of CD44v6/v7 for risk stratification. Reverse transcription polymerase chain reaction (RT-PCR) followed by PCR product purification, ligation into T vectors and positive clone sequencing were used to detect CD44 v6-containing variant isoforms in 23 APL patients. Real-time quantitative PCR of the CD44v6/v7 gene was performed in patients with APL and in NB4 cells that were treated with all-trans retinoic acid (ATRA) or arsenic trioxide ($As_2O_3$). Sequencing results identified four isoforms (CD44v6/v7, CD44v6/v8/v10, CD44v6/v8/v9/v10, and CD44v6/v7/v8/v9/v10) in bone marrow mononuclear cells of 23 patients with APL. The level of CD44v6/v7 in high-risk cases was significantly higher than those with low-risk. Higher levels of CD44v6/v7 were found in three patients with central nervous system relapse than in other patients inthe same risk group. Furthermore, in contrast to ATRA, only $As_2O_3$ could significantly down-regulate CD44v6/v7 expression in NB4 cells. Our data suggest that CD44v6/v7 expression may be a prognostic indicator for APL.

• Journal of Hospice and Palliative Care
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• v.17 no.2
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• pp.57-65
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• 2014

Purpose: Since most terminally ill cancer patients die of multiple organ failure, plasma endotoxin concentration levels may be used to predict the life expectancy. This study was performed to evaluate the clinical significance of endotoxin level in plasma as a prognostic factor for survival in patients with terminal cancer. Methods: This study was conducted with 56 terminally ill cancer patients, above 20 years old, from April 2009 through October 2009. Demographic characteristics, Karnofsky performance status, and survival time were evaluated. We analyzed blood levels of white blood cell hemoglobin, hematocrit, aspartate aminotransferase, alanine aminotransferase, c-reactive protein, total bilirubin and endotoxin in each patient. Results: We considered following variable for univariate analysis: plasma endotoxin level, sex, age, WBC, hemoglobin, hematocrit, AST, ALT, total bilirubin, CRP and severity of pain. Univariate analysis did not show a significant association between plasma endotoxin level and survival time. However, in a multivariate analysis with factors that were found to be significantly associated with survival sex, WBC count and total bilirubin level in univariate analysis, high levels of plasma endotoxin and short survival time were significantly related. Conclusion: Plasma endotoxin level could be used as a prognostic factor to predict the life expectancy of terminally ill cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3173-3178
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• 2012

The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3369-3375
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• 2014

Background: C-reactive protein (CRP), considered as a prototypical inflammatory cytokine, has been proposed to be involved in tumor progression through inflammation. Recent studies have indicated CRP as a progostic predictor for urological cancers, but the results remain controversial. Materials and Methods: A systematic search of Medline, Scopus and the Cochrane Library was performed to identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes of interest were collected from studies comparing overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were used for the effect size estimate. Results: A total of 43 studies (7,490 patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for PC). Our pooled results showed that elevated serum CRP level was associated with poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47), respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP expression could strongly predict poorer survival in urological cancers. Simultaneously, elevated serum CRP was also significantly associated with poor prognosis in the subgroup analysis. Conclusions: Our pooled results demonstrate that a high serum level of CRP as an inflammation biomarker denotes a poor prognosis of patients with urological cancers. Further large prospective studies should be performed to confirm whether CRP, as a biomarker of inflammation, has a prognostic role in urological cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.903-907
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• 2015

Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer, more than half are also hormone receptor (HR)-positive. Although HR is a predictive factor for the efficacy of hormone therapy, there are still some uncertainties in regard to the effects on patients with HR-positive and HER2-positive metastatic breast cancers due to the potential resistance to hormone therapy caused by co-expression of HR and HER2. There are no clinical trials directly comparing the efficacy of hormonal therapy with chemotherapy. Materials and Methods: To examine the real-world effect of hormone therapy on patients with HR-positive and HER2-positive metastatic breast cancers, a cross-sectional study of a representative sample of the Chinese population was conducted. The study included 113 patients who received first-line and second-line palliative treatment between 2005 and 2010 in the Cancer Institute and Hospital, Chinese Academy of Medical Science. The effect of hormone therapy on overall survival (OS) was studied. Results: The patients who received hormone therapy (n=51) had better overall survival in contrast to those who received chemotherapy with anti-HER2 therapy (n=62) in first- or second-line treatment. The difference was of borderline statistical significance (51.8m vs 31.9m, p=0.065). In addition, the effect of hormone therapy did not differ significantly with other prognostic factors, including age (${\leq}50$ years or >50 years), disease free survival (${\geq}2$ years or < 2 years) and site of metastasis (visceral or bone/soft tissue). On multivariate analysis, administration of hormone therapy was associated with a trend toward a favorable prognosis (p=0.148, HR=0.693, 95%CI 0.422-1.139). Age more than 50 years was the sole independent harmful prognostic factor (p<0.001, HR=2.797, 95%CI 1.676-4.668). Conclusions: Our data suggest that hormonel therapy may improve outcomes of the patients with ER-positive and HER2-positive metastatic breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.999-1003
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• 2014

Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.