• Journal of Chest Surgery
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• v.37 no.5
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• pp.423-431
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• 2004

Background : Tumor size in lung cancer is not as good a prognostic factor for adenocarcinoma as it is for other types of lung cancer; therefore it is difficult to estimate the prognosis preoperative. However, there have recently been some reports on the radiologic findings correlating to the clinicopathologic prognostic factors in peripheral small adenocarcinoma of lung. We tried to evaluate the prognostic importance of High-Resolution CT (HRCT) findings of such adenoearcinoma, Material and Method: One houndred and seventy-six surgically resected small peripheral adenocarcinoma measuring 3 cm or less in greatest dimension were reviewed radiologically and clinicopathologically. Result: The patients with greater extent of ground-glass attenuation (GGA) had better clinico-pathological factors. The tumors with gross appearance of GGA or bubble-like shape showed better clinicopathological prognostic factors than scar-like or solid shape. Conclusion: HRCT findings of small peripheral adenocarcinomas of the lung correlated well with the histologic and clinical prognostic factors. We can predict the post-operative prognosis with the radiologic findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5271-5276
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• 2014

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important protein kinase and a member of the MAPK family, which regulates cellular responses to environmental stress and serves as key integration points along the signal transduction cascade that not only link diverse extracellular stimuli to subsequent signaling molecules but also amplify the initiating signals to ultimately activate effector molecules and induce cell proliferation, differentiation and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3 and survivin in cervical cancer. MEKK3 and survivin expression was measured by RT-PCR and Western blotting of fresh surgical resections from 30 cases of cervical cancer and 25 cases of chronic cervicitis. Protein expression was detected by tissue microarray and immunochemistry (En Vision) in 107 cases of cervical cancer, 86 cases of cervical intraepithelial neoplasia (CIN), and 35 cases of chronic cervicitis. Expression patterns were analyzed for their association with clinicopathological factors and prognosis in cervical cancer. Expression of MEKK3 and survivin mRNA was significantly higher in cervical cancer than in the controls (p<0.05). MEKK3 and survivin expression differed significantly between cervical carcinoma, CIN, and cervicitis (p<0.05) and correlated with clinical stage, infiltration depth, and lymph node metastasis (p<0.05). MEKK3 expression was positively correlated with survivin (p<0.05). Kaplan-Meier survival analysis showed that MEKK3 and survivin expression, lymph node metastasis, depth of invasion, and FIGO stage reduce cumulative survival. Cox multivariate regression analysis showed that MEKK3, survivin, and clinical staging are independent prognostic factors in cervical cancer (p<0.05). Expression of MEKK3 and survivin are significantly increased in cervical cancer, their overexpression participating in the occurrence and development of cervical cancer, with protein expression and clinical staging acting as independent prognostic factors for patients with cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2985-2990
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• 2012

Background: Hepatocellular carcinoma (HCC), the main malignant tumor of the liver, is very common and highly lethal. The aim of this study was to determine its clinicopathologic characteristics and risk factors in Turkey. Materials and methods: In this study, patients who were diagnosed as suffering from HCC in the period between August 2004 and December 2011 were evaluated retrospectively. Results: A total of 98 patients were included, with a median age 61 (range: 16 to 82). Seventy nine (80.6%) were male 59 (60.2%) were infected with hepatitis B virus (HBV) and 15 (15.3%) with HCV, another 15 (15.3%) being alcohol abusers. Seventy two (73.5%) were at advanced stage and 54 (55.1%) had elevated serum alpha-fetoprotein (AFP). Surgery, chemoembolization, systemic chemotherapy and application of the tyrosine kinase inhibitor sorafenib were the major treatment options. Conclusions: According to our findings HCC is mostly diagnosed in advanced stage and age, being five times more common in males than females. Main risk factors of HCC are HBV infection, HCV infection and alcohol abuse. Elevation in AFP may facilitate early diagnosis of HCC in high risk groups.

• Molecules and Cells
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• v.24 no.3
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• pp.364-371
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• 2007

The tumor suppressor gene Ras association domain family 1A (RASSF1A) is highly methylated in a wide range of human sporadic tumors. The current study investigated the hypermethylation of RASSF1A, the expression of RASSF1A protein, and the correlation between these and the clinicopathological features of gallbladder (GB) cancer in Korean patients. Formalin-fixed, paraffin-embedded tumors and non-neoplastic GB tissues (22 carcinomas, 8 adenomas, 26 normal epithelia) were collected from patients who had undergone surgical resection. The methylation status of two regions of the RASSF1A CpG island was determined by methylation-specific PCR (MSP), and the expression of RASSF1A protein was examined by immunohistochemistry using tissue microarrays. The K-RAS mutation was analyzed by direct sequencing. Methylation of the RASSF1A promoter (region 1) was detected in 22.7% (5/22) of carcinomas, 12.5% (1/8) of adenomas, and 0% (0/26) of normal gallbladder epithelia (P = 0.025). Methylation of the first exon (region 2) was found in 36.4% (8/22) of carcinomas, 25.0% (2/8) of adenomas, and 8.0% (2/26) of normal gallbladder epithelia (P = 0.038). K-RAS mutations were present in 4.5% (1/22) of carcinomas and 25% (2/8) of adenomas. RASSF1A methylaton was not associated with clinicopathological factors or K-ras mutation. Reduction or loss of RASSF1A expression was observed in most methylated adenocarcinomas. Three RASSF1A-expressing human biliary tract cancer cell lines examined contained unmethylated promoters and exons 1. These results suggest that downregulation of RASSF1A expression by DNA hypermethylation may be involved in GB carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9927-9931
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• 2014

The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinoma of the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings. Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakin antibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levels in patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normal controls (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelial carcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were 83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients with muscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportional hazards regression analysis, none of the clinicopathological factors was associated with an increased risk for progression and cancer-specific survival. Examination of the serum periplakin level may play a role as a non-invasive diagnostic modality to aid urine cytology and cystoscopy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7737-7741
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• 2013

Background: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. Materials and Methods: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. Results: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. Conclusions: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2777-2783
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• 2015

Background: Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. Materials and Methods: The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. Results: Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. Conclusions: Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.583-587
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• 2013

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) using the Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationship to other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eighty node-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by the Chalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumor size, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis, the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.55), lymphovascular invasion (OR 3.46, 95% CI 1.13-10.58), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillary lymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis. However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared to H and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIS can be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship was identified between LVD and clinicopathological variables, including axillary lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6221-6225
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• 2012

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.

• 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.