• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6721-6726
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• 2014

Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and $500{\mu}g/day$) groups of six animals each, and another group (n=6) treated with TAM $100{\mu}g/day$ at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.867-872
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• 2012

Background: $FOXP3^+$ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. Design: Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect $FOXP3^+$ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. Results: The presence of $FOXP3^+$ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between $FOXP3^+$ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between $FOXP3^+$ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. Conclusions: In this study, a positive correlation between the presence of $FOXP3^+$ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1429-1434
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• 2014

Background: Owing to the variability of histopathological features and biological behaviour in gastric carcinoma, a great number of categorisation methods such as classical histopathologic grading, Lauren classification, the TNM staging system and the newly presented Goseki grading method are used by pathologists and other scientists. In our study, we aimed to investigate whether Goseki grade and tumour location have an effects on survival of gastric cancer cases. Materials and Methods: Eighty-four patients with gastric adenocarcinoma were covered in the investigation. The importance of Goseki grading system and tumour location were analysed in addition to the TNM staging and other conventional prognostic parameters. Results: The median survival time in our patients was 35 months (minimum: 5, maximum: 116). According to our findings, there was no relation between survival and tumour size (p=0.192) or classical histological type (p=0.270). In contrast, the Goseki grade and tumour location significantly correlated with survival (p=0.007 and p<0.001, respectively). Additionally, tumours of the intestinal type had a longer median survival time (60.0 months) than diffuse tumours (24.0 months). Conclusions: In addition to the TNM staging system, tumour location and the Goseki grading system may be used as significant prognostic parameters in patients with gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4963-4965
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• 2012

Objective: To diagnose renal cell carcinoma at early stages and for better prognosis, the main objective of our current study was to understand any association with diabetes with relation to age, gender, history of disease, diabetic laboratory parameters, tumor size and grade. Materials and Methods: This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between $1^{st}$ December, 2011 and $31^{st}$ May, 2012. The variables collected were age, gender, HbA1c, serum creatinine, fasting blood glucose. One way ANOVA was applied to examine statistical significance of differences between groups. The LSD post hoc test was used for the comparison of means of case groups. Results: Of the total 140 cases of renal cell carcinoma, 79 patients were also suffering from diabetes mellitus. The number of females (47) was more in diabetic RCC patients when compared to males (32). Significance was observed in levels of serum creatinine for tumor size >10cm ($0.0001^*$). The highest value of glycated hemoglobin (8.9%) and fasting blood sugar(148.3mg/dl)in cases of renal cell carcinoma along with diabetes mellitus was found in tumour size of 1-5cm. Conclusion: Diabetes mellitus has independent prognostic significance in RCC in relation to tumour size and grade.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2473-2476
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• 2012

Background: In papillary and follicular thyroid cancers (PTC, FTC), nodal and distant metastasis are generally considered important determinants of recurrence and survival, respectively. However, there is no consensus about the threshold primary tumour size (PTS) for these determinants. The aim of this study was to assess size relationships for developing nodal, pulmonary, bone and overall distant metastases. Methods: This prospective study covered 139 (93 females and 46 males) consecutive biopsy proven patients with PTC (114/139, mean age $41.0{\pm}15.7$ years, M: F, 35%:65%) and FTC (25/139, mean age $39.2{\pm}14.3$ years, M: F: 24%:76%). Results: Average primary tumor size was $23.4{\pm}11.1$ mm and $26.5{\pm}13.1$ mm for PTC and FTC respectively (p value=0.223). Nodal metastasis was found more common in PTC than FTC (49% vs 28%, p value <0.05), whereas overall distant metastasis was approximately the same (13% and 24%, p value=0.277); however, bone metastasis was significantly higher in FTC than PTC (24% vs 5%, p value <0.05). Cumulative risk for nodal and distant metastases for FTC and PTC starts at PTS <20 mm and may indicate an unusual aggressive tumor behavior in the studied population. Highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC was found to be ${\geq}50$ mm PTS. Conclusion: We conclude that a PTS of <20 mm may indicate an unusual aggressive tumor behavior with highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC with a cutoff of ${\geq}50$ mm.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2675-2677
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• 2015

Background: Depending on various pathological factors, non muscle invasive bladder cancer (NMIBC) shows varying degrees of recurrence. The aim of this study was to determine the incidence of recurrence of NMIBS in our centre, study the influence of intrinsic tumour characteristics like grade, stage, size and number, and compare our results with data in the published literature. Materials and Methods: A hospital based retrospective study was conducted on patients who underwent treatment for NMIBC from 2011 to 2014. The factors studied were number, size, grade, stage and site for correlation with recurrence. Statistical analysis was performed using Medcalc version 12, using Pearson's Chi square test to ascertain associations between variables. Results: A total of 73 patients with NMIBC were studied of which 48 (65.8%) had low grade and 25 (34.2%) had high grade tumours. Some 38 patients (52.1%) had Ta tumours, 34 (46.6%) had T1 and one had CIS. Mean follow up was 34.3 months. Recurrence rates were found to be 33.3% in low grade and 52.0% in high grade tumours. The overall recurrence rate in our centre was 39.7%. Significant correlations were seen between stage and recurrence, with a rate of 15% for Ta and 63.3% for T1 tumours. Fourteen out of 21 bladder cancers (66.6%) with multiple tumours demonstrated recurrence (p=0.006). Grade, size and site had no influence. Conclusions: In our study, recurrence of NMIBC was found to be directly proportional to stage and number of primary tumours, but not grade, size and site. The incidence of recurrence of NMIBC both stage wise and grade wise in our centre was also low compared to the data in the published literature.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1553-1558
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• 2015

Background: COX-2 has been shown to play an important role in the development of breast cancer and increased expression has been mooted as a poor prognostic factor. The purpose of this study was to investigate the relationship between COX-2 immunohistochemical expression and known predictive and prognostic factors in breast cancer in a routine diagnostic histopathology setting. Materials and Methods: Formalin-fixed paraffin-embedded tumour tissue of 144 no special type (NST) invasive breast carcinomas histologically diagnosed between January 2009 and December 2012 in Hospital Sultanah Bahiyah, Alor Setar, Kedah were immunostained with COX-2 antibody. COX-2 overexpression was analysed against demographic data, hormone receptor status, HER2-neu overexpression, histological grade, tumour size and lymph node status. Results: COX-2 was overexpressed in 108/144 (75%) tumours and was significantly more prevalent (87%) in hormone receptor-positive tumours. There was no correlation between COX-2 overexpression and HER2/neu status. Triple negative cancers had the lowest prevalence (46%) (p<0.05). A rising trend of COX-2 overexpression with increasing age was observed. There was a significant inverse relationship with tumour grade (p<0.05), prevalences being 94%, 83% and 66% in grades 1, 2 and 3 tumours, respectively. A higher prevalence of COX-2 overexpression in smaller size tumours was observed but this did not reach statistical significance. There was no relationship between COX-2 expression and lymph node status. Conclusions: This study did not support the generally held notion that COX-2 overexpression is linked to poor prognosis, rather supporting a role in tumorigenesis. Larger scale studies with outcome data and basic studies on cancer pathogenetic pathways will be required to cast further light on whether COX-2 inhibitors would have clinical utility in cancer prevention or blockage of cancer progression. In either setting, the pathological assessment for COX-2 overexpression in breast cancers would have an important role in the selection of cancer patients for personalized therapy with COX-2 inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3575-3581
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• 2016

Background: Cancer survival analysis is an essential indicator for effective early detection and improvements in cancer treatment. This study was undertaken to document colorectal cancer survival and associated prognostic factors in Malaysians. Materials and Methods: All data were retrieved from the National Cancer Patient Registry-Colorectal Cancer. Only cases with confirmed diagnosis through histology between the year 2008 and 2009 were included. Retrieved data include socio-demographic information, pathological features and treatment received. Survival curves were plotted using the Kaplan-Meier method. Univariate analysis of all variables was then made using the Log-rank test. All significant factors that influenced survival of patients were further analysed in a multivariate analysis using Cox' regression. Results: Total of 1,214 patients were included in the study. The overall 3- and 5-year survival rates were 59.1% and 48.7%, respectively. Patients with localized tumours had better prognosis compared to those with advanced stage cancer. In univariate analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p=0.001) were found to be predictors of survival. None of the socio-demographic characteristics were found to exert any influence. In Cox regression analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p<0.001) were determined as independent prognostic factors of survival after adjusted for age, gender and ethnicity. Conclusions: The overall survival rate for colorectal cancer patients in Malaysia is similar to those in other Asian countries, with staging at diagnosis, primary tumor size, involvement of lymph node and treatment modalities having significant effects. More efforts are needed to improve national survival rates in future.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3713-3716
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• 2012

Objective: Transmembrane protein 166 (TMEM166) expression in esophageal squamous cell carcinoma (ESCC) and remote normal esophageal tissues was examined to assess any role in tumour biology. Methods: TMEM166 mRNA expression in 36 cases with ESCC (36 tumour samples, 36 remote normal esophageal tissue samples) was detected by RT-PCR. TMEM166 protein expression was analysed in paraffin-embedded tissue samples from the same cases by immunohistochemistry. Results: Semi-quantitative analysis showed TMEM166 mRNA expression in ESCCs to be significantly lower than in remote normal esophageal tissues ($0.759{\pm}0.713$ vs. $2.622{\pm}1.690$, P=0.014). TMEM166 protein expression was also significantly reduced (69.4% vs. 94.4%, P<0.01). Conclusion: TMEM166 mRNA and protein expression demonstrated significant reduction in ESCCs compared with remote esophageal tissues, albeit with no correlation with tumour size, differentiation, stage, and lymph node metastasis, suggesting a role in regulating autophagic and apoptotic processes in the ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1725-1730
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• 2014

Management of patients with stage II colorectal carcinomas remains challenging as 20 - 30% of them will develop recurrence. It is postulated that these patients may harbour nodal micrometastases which are imperceptible by routine histopathological evaluation. The aims of our study were to evaluate (1) the feasibility of multilevel sectioning method utilizing haematoxylin and eosin stain and immunohistochemistry technique with cytokeratin AE1/AE3, in detecting micrometastases in histologically-negative lymph nodes, and (2) correlation between nodal micrometastases with clinicopathological parameters. Sixty two stage I and II cases with a total of 635 lymph nodes were reviewed. Five-level haematoxylin and eosin staining and one-level cytokeratin AE1/AE3 immunostaining were performed on all lymph nodes retrieved. The findings were correlated with clinicopathological parameters. Two (3.2%) lymph nodes in two patients (one in each) were found to harbour micrometastases detected by both methods. With cytokeratin AE1/AE3, we successfully identified four (6.5%) patients with isolated tumour cells, but none through the multilevel sectioning method. Nodal micrometastases detected by both multilevel sectioning and immunohistochemistry methods were not associated with larger tumour size, higher depth of invasion, poorer tumour grade, disease recurrence or distant metastasis. We conclude that there is no difference between the two methods in detecting nodal micrometastases. Therefore it is opined that multilevel sectioning is a feasible and yet inexpensive method that may be incorporated into routine practice to detect nodal micrometastases in centres with limited resources.