• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.369-377
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• 2018

Background: Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy. Methods: Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalin-fixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome. Results: High cytoplasmic CXCR4 expression was associated with younger age (p=.008), higher histologic grade (p=.007) and lower pathologic stage (p=.045), while high CXCL12 expression was related to larger tumor size (p=.045), positive lymph node metastasis (p=.005), and higher pathologic stage (p=.017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p=.006) and better recurrence-free survival (RFS) (log-rank p=.020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p=.019) and RFS (p=.038) after multivariate analysis. Conclusions: High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.

• Journal of Chest Surgery
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• v.52 no.5
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• pp.342-352
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• 2019

Background: Smokers with lung adenocarcinoma have a worse prognosis than those who have never smoked; the reasons for this are unclear. We aimed to elucidate the impact of smoking on patients' prognosis and the association between smoking and clinicopathologic factors, particularly histologic subtypes. Methods: We reviewed the records of 233 patients with pathologic stage T1-4N0-2M0 lung adenocarcinomas who underwent surgery between January 2004 and July 2015. The histologic subtypes of tumors were reassessed according to the 2015 World Health Organization classification. Results: In total, 114 patients had a history of smoking. The overall survival probabilities differed between never-smokers and ever-smokers (80.8% and 65.1%, respectively; p=0.003). In multivariate analyses, the predominant histologic subtype was an independent poor prognostic factor. Smoking history and tumor size >3 cm were independent predictors of solid or micropapillary (SOL/MIP)-predominance in the logistic regression analysis. Smoking quantity (pack-years) in patients with SOL/MIP-predominant tumors was greater than in those with lepidic-predominant tumors (p=0.000). However, there was no significant difference in smoking quantity between patients with SOL/MIP-predominant tumors and those whose tumors had non-predominant SOL/MIP components (p=0.150). Conclusion: Smoking was found to be closely associated with SOL/MIP-predominance in lung adenocarcinoma. Greater smoking quantity was related to the presence of a SOL/MIP component.

• Journal of Chest Surgery
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• v.56 no.6
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• pp.403-411
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• 2023

Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). Conclusion: After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.243-247
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• 2006

$\underline{Purpose}$: To evaluate the treatment results and prognostic factors of palliative radiation therapy in the patients with unresectable advanced pancreatic cancer. $\underline{Materials\;&\;Methods$: Thirty-seven evaluable patients with unresectable advanced pancreatic cancer who were treated by palliative radiation therapy for pain relief at the Department of Radiation Oncology, Kangnam St. Mary's hospital, the Catholic University of Korea between March 1984 and February 2005 were analysed retrospectively. There were 22 men and 15 women. Age at diagnosis ranged from 30 to 80 (median 57) years. Twelve patients (32.4%) had liver metastases and 22 patients (59.5%) had lymph node metastases. Radiation therapy was delivered to primary tumor and regional lymph nodes with $1{\sim}2\;cm$ margin, and total dose was $3,240{\sim}5,580\;cGy$ (median 5,040 cGy). Chemotherapy with radiotherapy was delivered in 30 patients (81%) with 5-FU alone (21 patients) or gemcitabine (9 patients). The follow-up period ranged from 1 to 44 months. Survival and prognostic factors were analysed using Kaplan-Meier method and log-rank test respectively. $\underline{Results}$: Overall mean and median survival were 11 and 8 months and 1-year survival rate was 20%. Among 33 patients who were amenable for response evaluation, 7 patients had good response and 22 patients had fair response with overall response rate of 87.9%. Mild to moderate toxicity were observed in 14 patients with nausea, vomiting, and indigestion, but severe toxicity requiring interruption of treatment were not observed. Chemotherapy didn't influence the survival and symptomatic palliation, but the group containing gemcitabine showed a tendency of longer survival (median 12 months) than 5-FU alone group (median 5.5 months) without statistical significance (p>0.05). The significant prognostic factors were Karnofsky performance status and liver metastasis (p<0.05). Age, sex, tumor location, lymph node metastasis, and CA 19-9 level did not show any prognostic significance (p>0.05). $\underline{Conclusion}$: Radiation therapy was effective for symptomatic palliation in the patients with unresectable advanced pancreatic cancer and would play an important part in the survival benefit with gemcitabine or other targeted agents.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.56-64
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• 2008

Purpose: Cathepsin D(CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Materials and Methods: Eighty-nine patients with locally advanced rectal cancer(cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Results: Positive CD expression was found in 57(64%) of the tumors and 32(35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression(p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival(OS) and disease-free survival(DFS) rates were not different between tumor CD-negative and positive patient biopsy samples(69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients(p=0.013). Conclusion: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.1
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• pp.84-90
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• 1995

To evaluate the role of radiation and chemotherapy after limb-saving operation in the management of soft tissue sarcoma, the authors analysed retrospectively 33 patients treated in department of Orthoaepdic Surgery and Radiation Therapy, Catholic University Medical College, in terms of survival rate, local recurrence rate and prognostic factors. There were 16 males and 17 females. The age distribution ranged from 16 to 81 years with mean age of 48. The follow-up period ranged from 2 to 10 years with average of 5.5 years. The histologic diagnoses were 9 liposarcoma(27.2%), 8 malignant fibrohistiocytoma(24.2%), 7 unclassifiable(21.2%), 3 rhabdomyosarcoma(9.1%), 2 malignant schwannoma, 2 synovral sarcoma, and 2 fibrosarcoma(6.1%) in orders. While marginal and intralesional margins were gained in 24 patients(72.7%), wide and radical margins were obtained only in 9 patients(27.3%). On postoperative 3 weeks, local irradiation of 5000-7000 cGy was delivered to all patients by shrinking field technique for 5-8 weeks. Of 33 patients, 16(45.5%) patients were received adjuvant chemotherapy in combination of adriamycin, cyclophosphamide & vicristine, or VP16 & ifosfamide based on histologic type and obtained surgical margin. The survival rates by direct method at 2 years and 5 years were 58% and 37% respectively. Local recurrences occured in 15 patients(45.5%) at average 16 months after operation. Survival rates at 2 years and 5 years were 37% and 22% in case of intralesional and manginal excision, 75% and 47% in case of wide and radical excision respectively with statistical significance(p<0.05). They were 25% and 17% in the presence of local recurrence, 67% and 42% in the absence of local recurrence respectively with statistical significance(p<0.05). Even though there was no statistical correlation between survival rate and tumor size(p>0.05), the authors considered tumor size as a significant prognostic factors as well as surgical margin and the presence of local recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6447-6453
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• 2012

Background: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. Methods: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. Results: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). Conclusion: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.169-177
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• 2004

Background : Cyclooxygenase is the main target enzyme for the nonsteroidal anti inflammatory drugs (NSAIDs) that have been shown to suppress carcinogenesis in both experimental models and epidemiological studies. COX-2 plays an important role in solid tumor growth, invasiveness and angiogenesis, through, in part, the synthesis of prostaglandins, such as prostaglandin E2 (PGE2). In this study, the prognostic significance of an increase in COX-2 expression in lung cancer samples was evaluated. Material and Methods : The expression of COX-2, by immunohistochemistry, was studied in paraffin-embedded tumor blocks obtained from 84 patients(male 67, female 17, with a mean age of 63, ranging from 34 to 84 years) who had undergone surgery at Wonkwang University Hospital, between 1997 and 2002. For the evaluation of the relationships between COX-2 expression, and the clinical stage, metastasis to lymph nodes and survival, those cases showing the respective antigen expression in >10% of the tumor cells were considered positive. Result : Of the 84 patients, 61 (73%) exhibited more than 10% COX-2 immunoreactivities in the tumor and normal cells, whereas the remaining 23 showed no increase in the expression of COX-2. There was no significant relationship between the increased expression of COX-2 and the disease stage(p=0.1002) or cell type(p=0.152). The median survival was longer for the patients with a negative, compared to positive, COX-2 expression(36 compared to 24 months, p<0.05). The two year-survival rate was also higher in the patients with a negative COX-2 expression (78%) than those with a positive expression (47%, Kaplan-Meier, Log Rank, p < 0.05). Conclusion : The median survival was longer in the patients with a negative, compared to positive, COX-2 expression was longer than those with positive COX-2, having undergone complete resection due to primary non-small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4421-4427
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• 2015

Objectives: To investigate the prognosis significance of preoperative serum alpha-fetoprotein (AFP) and the correlation with clinicopathological factors of hepatocellular carcinoma (HCC) patients who underwent hepatectomy. Materials and Methods: Clinicopathological data of retrospective analysis were collected for 251 HCC patients undergoing hepatectomy in this study. According to preoperative AFP level, patients were categorized into AFP-negative (0-20ng/mL) and AFP-positive (>20 ng/mL) groups for Kaplan-Meier analysis and Cox proportional hazard regression modeling. Results: The results demonstrated that increased AFP was associated with longer prothrombin time (PTs), liver capsule invasion, low grade differentiation, and late Barcelona Clinic Liver Center (BCLC) stage. Moreover, the female patients had a greater prevalence of increased preoperative AFP than male patients [284.8 (3.975-3167.5) vs (3.653-140.65); Z-2.895, p=0.004]. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 78.1, 57.5, and 40.6 % in the AFP-negative group and 61.8, 37.7, and 31.4 %, respectively, in the AFP-positive group (log-rank test 8.312, p=0.004). The 1-, 3-, and 5-year overall survival (OS) rates were 94.4, 83.8, and 62.3% in the AFP-negative group and 87.2, 60.0, and 36.7%, respectively, in the AFP-positive group. The difference was statistically significant (log-rank test, 16.884, p=0.000). Cox proportional-hazards model identified preoperative AFP to be an independent prognostic predictor of overall survival. Conclusions: Preoperative serum AFP is an independent predictor of prognosis among HCC patients following surgical resection. Female patients have a higher preoperative AFP than their male counterparts.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.164-167
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• 2011

Objective: There are limited data regarding the significance of elevated serum CA-125 level during IUI cycles, even though it is used widely during the initial evaluation of infertile patients. The aim of this study was to investigate the prognostic value of serum CA-125 levels during IUI cycles. Methods: Among the patients with controlled ovarian stimulation and IUI cycles at Seoul National University Hospital from Jan 2005 through Dec 2009, 92 cases with no identified endometriotic lesion, ovarian tumor, salpingeal lesion, or uterine myoma were selected. To compare the clinical characteristics between the pregnancy group and the non-pregnancy group, the Mann-Whitney U test and Fisher's exact test were used. Results: The overall pregnancy rate was 18.5% (17/92). The pregnancy group showed a higher number of follicles 16 mm in diameter ($p$=0.036), endometrial thickness ($p$ <0.001), ampules of gonadotropin ($p$=0.009), and higher body mass index ($p$=0.022) than the non-pregnancy group. No significant difference was observed in the serum CA-125 level or the proportion of patients with CA-125 exceeding 17 IU/mL between the two groups. Conclusion: The prognostic value of serum CA-125 level among infertile patients with IUI cycles is considered limited.