• Korean Journal of Radiology
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• 제22권11호
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• pp.1797-1808
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• 2021

Objective: To determine whether volumetric CT texture analysis (CTTA) using fully automatic tumor segmentation can help predict recurrence-free survival (RFS) in patients with intrahepatic mass-forming cholangiocarcinomas (IMCCs) after surgical resection. Materials and Methods: This retrospective study analyzed the preoperative CT scans of 89 patients with IMCCs (64 male; 25 female; mean age, 62.1 years; range, 38-78 years) who underwent surgical resection between January 2005 and December 2016. Volumetric CTTA of IMCCs was performed in late arterial phase images using both fully automatic and semi-automatic liver tumor segmentation techniques. The time spent on segmentation and texture analysis was compared, and the first-order and second-order texture parameters and shape features were extracted. The reliability of CTTA parameters between the techniques was evaluated using intraclass correlation coefficients (ICCs). Intra- and interobserver reproducibility of volumetric CTTAs were also obtained using ICCs. Cox proportional hazard regression were used to predict RFS using CTTA parameters and clinicopathological parameters. Results: The time spent on fully automatic tumor segmentation and CTTA was significantly shorter than that for semi-automatic segmentation: mean ± standard deviation of 1 minutes 37 seconds ± 50 seconds vs. 10 minutes 48 seconds ± 13 minutes 44 seconds (p < 0.001). ICCs of the texture features between the two techniques ranged from 0.215 to 0.980. ICCs for the intraobserver and interobserver reproducibility using fully automatic segmentation were 0.601-0.997 and 0.177-0.984, respectively. Multivariable analysis identified lower first-order mean (hazard ratio [HR], 0.982; p = 0.010), larger pathologic tumor size (HR, 1.171; p < 0.001), and positive lymph node involvement (HR, 2.193; p = 0.014) as significant parameters for shorter RFS using fully automatic segmentation. Conclusion: Volumetric CTTA parameters obtained using fully automatic segmentation could be utilized as prognostic markers in patients with IMCC, with comparable reproducibility in significantly less time compared with semi-automatic segmentation.

• Korean Journal of Radiology
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• 제21권8호
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• pp.946-954
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• 2020

Objective: To investigate preoperative magnetic resonance imaging (MRI) findings associated with resection margin status in patients with invasive lobular carcinoma (ILC) who underwent breast-conserving surgery. Materials and Methods: One hundred and one patients with ILC who underwent preoperative MRI were included. MRI (tumor size, multifocality, type of enhancing lesion, distribution of non-mass enhancement [NME], and degree of background parenchymal enhancement) and clinicopathological features (age, pathologic tumor size, presence of ductal carcinoma in situ [DCIS] or lobular carcinoma in situ, presence of lymph node metastases, and estrogen receptor/progesterone receptor/human epidermal growth factor receptor type 2 status) were analyzed. A positive resection margin was defined as the presence of invasive cancer or DCIS at the inked surface. Logistic regression analysis was performed to determine pre- and postoperative variables associated with positive resection margins. Results: Among the 101 patients, 21 (20.8%) showed positive resection margins. In the univariable analysis, NME, multifocality, axillary lymph node metastasis, and pathologic tumor size were associated with positive resection margins. With respect to preoperative MRI findings, multifocality (odds ratio [OR] = 3.977, p = 0.009) and NME (OR = 2.741, p = 0.063) were associated with positive resection margins in the multivariable analysis, although NME showed borderline significance. Conclusion: In patients with ILC, multifocality and the presence of NME on preoperative breast MRI were associated with positive resection margins.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4951-4956
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• 2014

Purpose: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. Methods: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. Results: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2-tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). Conclusion: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.

• Journal of Gastric Cancer
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• 제5권4호
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• pp.217-221
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• 2005

목적: 최근 평균수명의 증가로 고령자에서 위암 진단율이 증가하고 있으며, 수술방법 및 수술 전후 환자관리법이 발전함에 따라 수술적 치료의 적용이 점차 많아지고 있다. 저자들은 고령 위암환자들의 임상적 특징 및 수술에 따른 합병증 및 치료효과를 비고령군과 비교하여 고령 위암환자의 특성을 규명하고자 하였다. 대상 및 방법: 조선대학교병원 외과에서 1995년 3월부터 2002년 2월까지 위암으로 수술적 치료를 시행 받은 706명의 환자를 대상으로 의무기록 확인을 통한 후향적 방법을 사용하여 고령군(75세 이상)과 비고령군(75세 미만)을 임상적 특성, 수술의 근치도 및 술 후 합병증, 전체생존율에 따라 비교하였다. 결과: 임상적 특성에 해당하는 성별, 위암의 위치, 암의 침윤도, 림프절 절제범위, 조직학적 병기에서 고령군과 비고령군 간의 통계적 유의성은 없었다. 수술의 근치도와 수술 후 조기합병증의 발생 빈도에서도 두 군간의 통계적 유의성은 없었다. 결론: 위암발현 양상은 고령군과 비고령군에서 차이를 보이지 않았고, 수술적 근치도, 술 후 합병증, 전체생존율에서도 차이를 보이지 않았다 따라서 위암환자의 수술적 치료의 적용에서 고령은 제한인자가 아니며, 위암수술 후 예후에도 영향을 미치지 않는다는 결론을 내릴 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10577-10583
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• 2015

Background: Triple-negative breast cancer (TNBC), characterized by the lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2, is typically associated with a poor prognosis. The majority of TNBCs show the expression of basal markers on gene expression profiling and most authors accept TNBC as basal-like (BL) breast cancer. However, a smaller fraction lacks a BL phenotype despite being TNBC. The literature is silent on non-basal-like (NBL) type of TNBC. The present study was aimed at defining behavioral differences between BL and NBL phenotypes. Objectives: i) Identify the TNBCs and categorize them into BL and NBL breast cancer. ii) Examine the behavioral differences between two subtypes. iii) Observe the pattern of treatment failure among TNBCs. Materials and Methods: All TNBC cases during January 2009-December 2010 were retrieved. The subjects fitting the inclusion criteria of study were differentiated into BL and NBL phenotypes using surrogate immunohistochemistry with three basal markers $34{\beta}E12$, c-Kit and EGFR as per the algorithm defined by Nielsen et al. The detailed data of subjects were collated from clinical records. The comparison of clinicopathological features between two subgroups was done using statistical analyses. The pattern of treatment failure along with its association with prognostic factors was assessed. Results: TNBC constituted 18% of breast cancer cases considered in the study. The BL and NBL subtypes accounted for 81% and 19% respectively of the TNBC group. No statistically significant association was seen between prognostic parameters and two phenotypes. Among patients with treatment failure, 19% were with BL and 15% were with NBL phenotype. The mean disease free survival (DFS) in groups BL and NBL was 30.0 and 37.9 months respectively, while mean overall survival (OS) was 31.93 and 38.5 months respectively. Treatment failure was significantly associated with stage (p=.023) among prognostic factors. Conclusions: Disease stage at presentation is an important prognostic factor influencing the treatment failure and survival among TNBCs. Increasing tumor size is related to lymph node positivity. BL tumors have a more aggressive clinical course than that of NBL as shown by shorter DFS and OS, despite having no statistically significant difference between prognostic parameters. New therapeutic alternatives should be explored for patients with this subtype of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5165-5169
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• 2013

Background: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. Materials and Methods: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. Results: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). Conclusions: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma.

• Journal of Gastric Cancer
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• 제6권4호
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• pp.284-290
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• 2006

목적: 위암 발생에서 cyclooxygenase-2 (COX-2)가 혈관신생을 유도한다는 연구보고는 많으나 COX-2와 림프관신생과의 연관성은 잘 알려져 있지 않다. 이에 위암에서 COX-2와 VEGF-C의 상관관계 및 다른 임상병리학적 인자들과 비교 분석하여 COX-2가 림프관신생 및 전이를 유도하는지 여부를 알고자 하였다. 대상 및 방법: 1995년 7월부터 2001년 6월까지 본원에서 위암으로 진단받고 수술을 시행 받은 100명의 환자를 대상으로 COX-2와 VEGF-C에 대한 면역조직화학 검사를 시행하였으며, 이 두 인자들의 상관관계 및 성별, 병기, 림프절 전이, 종양 위치, Lauren 분류법, 혈관침범등과의 관계를 비교 분석하였다. 결과: COX-2는 86%, VEGF-C는 70%에서 양성 반응을 보였다. VEGF-C와 COX-2 모두 림프절 전이와 유의한 상관관계를 보였고(P=0.033 and P=0.012) VEGF-C와 COX-2의 발현은 밀접한 상관관계를 보였다(P=0.026). 그러나 다른 인자들과는 유의한 상관관계를 보이지 않았다. 결론: 위암환자에서 COX-2 발현은 VEGF-C 발현과 유의한 상관관계가 있었고, 이 두 인자들은 모두 림프절 전이와 연관이 있었다. 이에 COX-2 발현은 VEGF-C 발현을 매개로 림프관신생에 관여한다고 할 수 있겠다.

• Journal of Breast Cancer
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• 제21권4호
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• pp.406-414
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• 2018

Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

• Journal of Gastric Cancer
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• 제19권1호
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• pp.121-131
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• 2019

Purpose: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. Materials and Methods: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED ($P_{NED}$) and demographic and clinicopathological parameters. Results: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. $P_{NED}$, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff $P_{NED}$ was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher $P_{NED}$. Tumors with ${\geq}10%$ NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. Conclusions: GC with ${\geq}10%$ NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.