• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1243-1249
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• 2016

Background: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. Materials and Methods: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables. Results: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value. Conclusions: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7883-7887
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• 2015

Background: Colorectal cancer is one of the most common cancers worldwide. Viruses including human papillomavirus (HPV) have been reported to be associated with different cancers but any association with colorectal cancers remains controversial. Aim: To evaluate any association between HPV infection and adenocarcinoma of the colon and adenomatous polyps. Materials and Methods: Paraffin-embedded tissue specimens of 70 colorectal adenocarcinomas, 70 colorectal adenomatous polyps, and 70 colorectal normal tissues were subjected to DNA extraction. The quality of the extracted DNA was confirmed by amplification of a ${\beta}$-globin fragment using polymerase chain reaction (PCR). PCR using specific primers were performed to detect HPV DNA. Specific primers targeting the E6 region of the HPVs 16 and 18 were used for genotyping. Results: HPV DNA was detected in 2 (2.85%) out of 70 adenocarcinoma colorectal tissues and 4 (5.71 %) out of 70 adenomatous colorectal tissues. All normal colorectal tissues were negative for HPV DNA. HPV-16 was the most predominant genotype (5 sample) followed by HPV-18 (4 sample). Despite the above observations, statistical analyses indicated no significant differences in the frequencies of HPV positive subjects between the cancerous and normal samples. Conclusions: Although the differences observed in the frequencies of HPV positive cases in our study was not significant relative to those of control subjects, the fact of 6 positive samples among cancerous tissues, may still suggest a role of HPV in colorectal carcinogenesis. The study collectively indicated that some colorectal cancerous tissues are infected with high risk HPV genotype. The findings merit more investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4001-4005
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• 2012

Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs $28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1639-1644
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• 2012

The aim of this study was to investigate the expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer (PCa). Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 PCa, 40 benign prostatic hyperplasia (BPH) and 10 normal prostate specimens for this purpose. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for mRNA expression of mPGES-1 and Beclin-1, while MTT assays were used to ascertain the best working concentration of the mPGES-1 inhibitor (CAY10526). The effect of CAY10526 treatment on expression of Beclin-1 in DU-145 cells was studied using Western blot analysis. Localization of Beclin-1 and mPGES-1 was in endochylema. Significant differences in expression was noted among PCa, BPH and normal issues (P<0.05). Beclin-1 expression inversely correlated with mPGES-1 expression in PCa tissue (P<0.05). CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells (P<0.05), while increasing Beclin-1 levels (P<0.05). Overexpression of mPGES-1 could decrease the autophagic PCa cell death. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1. The results suggest that inhibition of mPGES-1 may have therapeutic potential for PCa in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6357-6362
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• 2012

Background: To determine the prevalence of mammalian target of rapamycin phosphorylation (p-mTOR) and vascular endothelial growth factor (VEGF) and any correlation with clinical characteristics and prognosis in ovarian clear cell carcinoma patients. Materials and Method: Seventy four paraffin-embedded specimens of such carcinomas frompatients who underwent surgery, received adjuvant chemotherapy and were followed up at King Chulalongkorn Memorial Hospital during January 2002 to December 2008 were stained with rabbit monoclonal IgG p-mTOR and rabbit polyclonal IgG VEGF using immunohistochemical methods. Medical records were reviewed and clinical variables were analysed. Results: The prevalence of positive p-mTOR in ovarian clear cell carcinoma was 87.9% and significantly higher in advance-stage than early-stage patients (100% versus 83.6%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with positive p-mTOR expression were 60% and 69.2% with no differences from patients with negative p-mTOR expression (p>0.05). The prevalence of VEGF expression was 63.5% and significantly higher in chemo-sensitive than chemo-resistant patients (70.7% versus 37.5%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with VEGF expression were 72.3% and 83% respectively which were significantly different from patients with negative VEGF expression (p<0.05). Conclusions: p-mTOR expression in ovarian clear cell carcinoma was significantly correlated with the stage of disease. VEGF expression was significantly correlated with chemosensitivity, and survival. Further studies of related targeted therapy might be promising.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7223-7228
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• 2014

The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p<0.05; log-rank test). Cancers with lower MYH11 expression were more likely to have a poor prognosis. Otherwise, MYH11 expression was unrelated to patient clinicopathological features. On multivariate analysis, low MYH11 expression proved to be an independent adverse prognosticator (p<0.05). These findings show that MYH11 can contribute to predicting prognosis in stage II and III colorectal cancers.

• Korean Journal of Head & Neck Oncology
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• v.20 no.2
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• pp.147-155
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• 2004

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck malignant tumor. The molecular genetic changes involving both oncogenes and tumor suppressor genes are known to be involved in head and neck squamous cell carcinogenesis, but the roles of the known tumor suppressor genes in carcinogenesis are not fully elucidated. The objectives of this study are to demonstrate the genetic alterations including the loss of heterozygosity (LOH) , amplification, and microsatellite instability of known tumor suppressor genes in HNSCC and to evaluate the relationship between genetic alterations of tumor suppressor genes and clinicopathologic features. Materials and Methods: Genetic alterations of 10 micro satellite markers of the 6 known tumor suppressor genes (APC, EXT1, DPC4, p16, FHIT, and PTEN) were analysed by DNA-PCR in paraffin-embedded histologically confirmed HNSCC specimens. Results: The genetic alterations of tumor suppressor genes were found frequently. Among the genetic alterations, LOH was most frequently found one. LOH was found frequently in APC (45.4%), EXT1 (36.4%), DPC4 (54.5%), and p16 (50%), but not found in FHIT. Also, the author found that abnormalities of APC gene was related to cervical lymph node metastasis and recurrence and that abnormalities of EXT1 gene were coexisted with those of APC gene or DPC4 gene. But these coexistences had no correlation with clinical features. Conclusion: These results suggested that APC, EXT1, p16, and DPC4 genes might play important roles and multiple tumor suppressor genes may participate dependently or independently in the carcinogenesis of HNSCC. These results also suggested that APC gene might relate to prognosis.

• The Journal of the Korean bone and joint tumor society
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• v.5 no.4
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• pp.221-228
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• 1999

The purpose of this study was to verify the importance of apoptosis in genesis of osteosarcoma and whether apoptosis may play an important role as a predictive factor for the response to chemotherapy. Of the patients who were diagnosed osteosarcoma between January 1995 and June 1999, ten patients were selected. All specimens were obtained before and after preoperative chemotherapy and examined for the occurrence of apoptosis. Apoptosis was investigated by in situ end-labeling technique on paraffin-embedded sections and apoptotic indices were calculated before and after chemotherapy. The ages of ten patients ranged from 15 to 59 with equal sex ratio. All patients completed the planned pre-operative chemotherapy. Apoptosis occurs in osteosarcoma and apoptotic indices are increased after chemotherapy. Mean apoptotic index (AI) before and after chemotherapy were 17.2 (range 6-28.9) and 26.3 (9.6-46.2), respectively. Apoptotic cells were usually present around the necrotic area. The AI was increased as the progression of stage and in responder group more than in non-responder. Apoptosis is induced by pre-operative chemotherapy and the response is variable. Changes in AI levels before and after chemotherapy may possibly predict an individual patient's overall response.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.373-376
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• 2015

Background: EVA1A (eva-1 homolog A) is a novel gene that regulates programmed cell death through autophagy and apoptosis. Our objective was to investigate the expression profiles and potential role of EVA1A in normal and neoplastic human pancreatic tissues. Materials and Methods: The expression pattern of EVA1A in normal pancreatic tissue was examined by indirect immunofluorescence and confocal microscopy. Protein levels in paraffin-embedded specimens from normal and diseased pancreatic and matched non-tumor tissues were evaluated by immunohistochemistry. Results: EVA1A colocalized with glucagon but not with insulin, demonstrating production in islet alpha cells. Itwas strongly expressed in chronic pancreatitis, moderately or weakly expressed in the plasma membrane and cytoplasm in pancreatic acinar cell carcinoma, and absent in normal pancreatic acinar cells. Although the tissue architecture was deformed, EVA1A was absent in the alpha cells of pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, mucinous cystadenomas, solid papillary tumors and pancreatic neuroendocrine tumors. Conclusions: EVA1A protein is specifically expressed in islet alpha cells, suggesting it may play an important role in regulating alpha-cell function. The ectopic expression of EVA1A in pancreatic neoplasms may contribute to their pathogenesis and warrants further investigation.

• 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.