• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2021-2026
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• 2014

Aim: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. Methods: We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. Results: NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). Conclusion: Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6065-6068
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• 2013

Background: Primary aim of this study is to assess whether or not there is an increase at rate of HPV positive oropharyngeal cancers during 1996-2011 in Turkey, for comparison with prior reports from Western countries. Materials and Methods: A total of 138 newly diagnosed patients with oropharyngeal cancer were identified, 39 of which had no primary tumor specimen available and 18 patients with invalid HPV status, therefore HPV status for remaining 81 patients was evaluated. The presence and type of HPV DNA were determined with formalin-fixed paraffin embedded specimens, using an HPV DNA-based multiplex PCR assay. Associations between HPV status and clinicopathological characteristics were evaluated using a two-sample t-test for the continuous variables and the categorical variables were compared by chi-square test. Overall survival (OS) periods were calculated with Kaplan-Meier method. Results: The proportion of HPV-positive cancer has continued to increase during 2004-2011 as compared with 1996-2003. Notably, 33% (6/18) of the cases were HPV-positive in 1996-1999, 43% (9/21) in 2000-2003, 55% (11/20) in 2004-2007 and 70% (16/23) in 2008-2011. Thus, when we compared the results obtained during the 2004-2011with results of 1996-2003 period, we found that increase at HPV-positivity ratio was statistically significant (38% vs 64% p=0.012). Conclusions: This study demonstrated that HPV positive oropharyngeal cancers are increasing in Turkish patients as in the Western world.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4717-4721
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• 2013

Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. Forty eight HNSCC patients were selected between 2006 and 2009 diagnosed at the Royal Darwin Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with negative surgical margins with hematoxylin and eosin (HandE) were chosedn for further analysis. A total of 77 surgical margins were obtained and subsequently analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal eIF4E antibodies. Contingency table and ${\chi}^2$-test were used to investigate the correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival of the HNSCC patients. The follow up period was 74 months (range 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4591-4594
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• 2013

Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This populationbased retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from $1^{st}$ January 2000 to $31^{st}$ December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan-Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2055-2060
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• 2016

Background: Colorectal cancer (CRC) is one of the most common causes of death worldwide and in Thailand. The X-ray repair cross-complementary protein 1 (XRCC1) is required for efficient DNA repair. The effects of this gene on survival in colorectal cancer remain controversial and have not been reported in Thailand. The aim of this study was to investigate the association of the XRCC1 gene with survival of colorectal cancer patients in a Thai population. Materials and Methods: Data and blood samples were collected from 255 newly diagnosed and pathologically confirmed CRC patients who were recruited during the period 2002 to 2006 and whose vital status was followed up until 31 October, 2014. Real-time PCR-HRM was used for genotype identification. The Kaplan-Meier method, the log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves and compare various survival distributions and adjusted hazard ratios. Results: Most of the cases were males, and the median age was 55 years. The median survival time was 2.43 years. The cumulative 1-, 3-, 5-, 7-, and 10 year survival rates were 76.70%, 39.25%, 26.50%, 16.60% and 3.56%, respectively. After adjustment, female gender, ages 50-59 and ${\geq}60years$, tumour stage III+IV, a signet-ring cell carcinoma, and poor differentiation had significant associations with increased risk of CRC death. While the XRCC1 Arg/Arg homozygote appeared to be a risk factor for CRC death, the association was not significant. Conclusions: The genetic variant in the XRCC1 may not be associated with the survival of CRC patients in Thailand. Further studies are needed to verify our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2165-2170
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• 2016

Background: The survival of hepatocellular carcinoma (HCC) patients is usually low due to late diagnosis. Cipto Mangunkusumo Hospital as the largest tertiary referral hospital in Indonesia, has recently improved its modalities for advanced HCC management, but there has not been any evaluation on any improvement in HCC patient survival. Materials and Methods: A retrospective analysis on 114 HCC patients in 2013-2014 were conducted and compared with the database for 77 HCC patients in 1998-1999. Clinical characteristics and treatment received were recorded and the survival of both groups was analyzed using the Kaplan-Meier method and compared using the log-rank test. Results: The percentage of HBV positive patients had increased after fifteen years from 32.5% to 67.5%. Only two patients (1.8%) in 2013-2014 were diagnosed with HCC during surveillance program. Proportions of Barcelona Clinic Liver Cancer A, B, C, and D in 2013-2014 were 1.8%, 42%, 28.1%, and 28.1%, respectively. There was an increase in the use of potentially curative treatment, such as surgical resection or combination of loco-regional therapies. The one-year survival rate increased from 24.1% in 1998-1999 to 29.4% in 2013-2014, while the median survival decreased from 146 days to 138 days, but the difference was not statistically significant (p=0.913). Conclusions: There was no improvement in the median survival of HCC patients after fifteen years because most continued to present at late stages. There is an urgent need for a nationwide implementation of a hepatitis screening program and HCC surveillance education.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1643-1649
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• 2015

Background: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/amplified (HER2+), the efficacy of trastuzumab treatment and survival results. Materials and Methods: Patients with HER2-positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. Results: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor. Conclusions: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.885-890
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• 2012

Background: Head and neck cancers are prevalent in Thailand, in particular in the southern region of the country. However, survival with a large data set has not been reported. The purpose of the present study was to evaluate the survival figures and the prognostic factors in a cohort of patients treated in a university hospital located in the south of Thailand. Patients and Methods: Consecutive new cases of primary carcinoma of the oral cavity, oropharyx, hypopharynx and larynx, treated at Songklanagarind Hospital during 2002 to 2004, were analyzed. The 5-year overall survival rates were obtained by the Kaplan-Meier method. Prognostic factors were identified through multivariate Cox regression analysis. Results: A total 1,186 cases were analyzed. Two-thirds (66.6%) of the cases were at advanced stage (stage III & IV) at presentation. The five-year overall survivals for the whole cohort, oral cavity, oropharynx, hypopharynx and larynx were 24.1%, 25.91%, 19.2%, 13.4%, 38.0% respectively. Stage and treatment type were strong prognostic factors for all sites. An age ${\geq}$ 80 years was associated with poor survival in oral cavity and larynx cancer. Conclusions: The results revealed remarkably poor outcomes of the patients in the series, indicating a strong need to increase the proportion of early stage presentations and maximize the treatment efficacy to improving outcomes. Very old patients are of particular concern for treatment care of oral cavity and larynx cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.821-825
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• 2012

Purpose: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Methods: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells. Results: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro. Conclusions: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.887-890
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• 2014

This study was undertaken to compare surgical outcomes and survival rates of patients with the 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIA1 versus IIA2 cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy (RHPL). Patients with stage IIA cervical cancer undergoing primary RHPL between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinicopathologic variables, i.e. nodal metastasis, parametrial involvement, positive surgical margins, deep stromal invasion (DSI)), lymph-vascular space invasion (LVSI), adjuvant treatment, and 5-year survival. The chi square test, Kaplan-Meier method and log-rank test were used for statistical analysis. During the study period, 133 women with stage IIA cervical cancer, 101 (75.9 %) stage IIA1, and 32 (24.1 %) stage IIA2 underwent RHPL. The clinicopathologic variables of stage IIA1 compared with stage IIA2 were as follows: nodal metastasis (38.6% vs 40.6%, p=0.84), parametrial involvement (10.9% vs 15.6%, p=0.47), positive surgical margins (31.7% vs 31.3%, p=1.0), DSI (39.6% vs 53.1%, p=0.18), LVSI (52.5% vs 71.9%, p=0.05) and adjuvant radiation (72.3% vs 84.4%, p=0.33). With a median follow-up of 60 months, the 5-year disease-free survival (84.6% vs 88.7%, p=0.67) and the 5-year overall survival (83.4% vs 90.0%, P=0.49) did not significantly differ between stage IIA1 and stage IIA2 cervical cancer. In conclusion, patients with stage IIA1 and stage IIA2 cervical cancer have comparable rates of locoregional spread and survival. The need for receiving adjuvant radiation was very high in both substages. The revised 2009 FIGO system did not demonstrate significant survival differences in stage IIA cervical cancer treated with radical hysterectomy. Concurrent chemoradiation should be considered a more suitable treatment for patients with stage IIA cervical cancer.