1.Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers.
Jung Ho KIM ; Jeong Mo BAE ; Hyeon Jeong OH ; Hye Seung LEE ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2015;49(2):118-128
BACKGROUND: Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. METHODS: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). RESULTS: Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin-based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin-based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. CONCLUSIONS: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC.
Cellular Structures
;
Chemotherapy, Adjuvant*
;
Colorectal Neoplasms*
;
Disease-Free Survival
;
Humans
;
Microsatellite Instability
;
Microsatellite Repeats
;
Multivariate Analysis
;
Pathology
;
Prognosis*
2.Unexpected Antibody Positivity with the Use of the LISS/Coombs Gel Test.
Tong Kil JUNG ; Nan Young LEE ; Hye Gyeong BAE ; Eun Hee KWON ; Sung Hwa PARK ; Jang Soo SUH
Korean Journal of Clinical Pathology 2001;21(5):422-425
BACKGROUND: There is a recent trend of increased use of the gel test for the detection of unexpected antibodies (Abs) because of its simplicity and ease with which definitive interpretation can be made. However, because of the low insurance payments in Korea, only the LISS/Coombs card is used and thus the detection rate of the cold Abs has decreased. We have studied the detection rates of the Abs in patients by using the LISS/Coombs gel test and thus evaluated the clinical usefulness of the LISS/Coombs gel test. METHODS: Abs screening tests have been carried out using the DiaMed(TM) LISS/Coombs gel card test (Murten, Switzerland) on 14,942 patients for whom blood transfusions were ordered between July 1, 1997 and March 31, 2001. When the test for Abs was positive, Ab identification tests were further carried out with the DiaMed(TM) LISS/Coombs gel card and the ID-DiaPanel 1-11. RESULTS: Eighty-one out of 14,942 patients (0.54%) revealed positive results. Of these, 15 showed anti-E, 5 showed anti-E+c, 4 showed anti-C, 3 showed anti-D, 2 showed anti-Jk(a), 1 each showed anti-c, anti-M, anti-Lu(a), and anti-K Abs. CONCLUSIONS: Although the detection rate for the cold Abs of the LISS/Coombs gel test was low, it is considered to be highly useful because of the high detection rate for the clinically important warm Abs, the simplicity in carrying out the test, and the easy readability of test results.
Antibodies
;
Blood Transfusion
;
Comprehension
;
Humans
;
Insurance
;
Korea
;
Mass Screening
3.Prognostic Significance of EPHB2 Expression in Colorectal Cancer Progression
Bo Gun JANG ; Hye Sung KIM ; Weon Young CHANG ; Jeong Mo BAE ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2018;52(5):298-306
BACKGROUND: A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC. METHODS: To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression. RESULTS: The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692). CONCLUSIONS: Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.
Adenoma
;
Colorectal Neoplasms
;
Humans
;
Immunohistochemistry
;
Ligands
;
Microsatellite Instability
;
Multivariate Analysis
;
Prognosis
;
Protein-Tyrosine Kinases
;
Real-Time Polymerase Chain Reaction
;
Receptor, EphB2
;
RNA, Messenger
4.Diagnostic predictability of self-reported questionnaire for periodontitis.
Hye Jung JIN ; Beak Il KIM ; Deok Young PARK ; Seong Hwa JEONG ; Kwang Hak BAE ; Jin Bom KIM ; Seung Hwa JEONG ; Hye Rin LEE ; Gyeong Ji WOO ; Youn Hee CHOI
Journal of Korean Academy of Oral Health 2015;39(1):63-68
OBJECTIVES: The present study aimed to evaluate the validity of a set of self-reported questionnaires for periodontitis for estimating the prevalence of chronic adult periodontitis in the Korean population. METHODS: The questionnaire is comprised of a total of 14 questions with four summarized concepts including self-diagnosis of oral status, subjective signs related to oral health, smoking and drinking status, and use of auxiliary oral hygiene devices including scaling. The predictiveness of the measures from these self-reported questions was assessed by logistic regression modeling using receiver operating characteristic (ROC) statistics, sensitivity, and specificity. RESULTS: The sensitivity, specificity, and AUC including all questions were 0.571, 0.768, and 0.781, respectively; the sum of sensitivity and specificity was 1.34. To gain robustness, a simplified predictive model was built with six questions. Its results were 0.536, 0.817, and 0.762 for sensitivity, specificity, and AUC, respectively. The sum of sensitivity and specificity was found to be 1.35. CONCLUSIONS: The self-reported questionnaire for periodontitis showed considerable validity, but further study is required to provide optimal validity and predictability.
Area Under Curve
;
Chronic Periodontitis
;
Drinking
;
Logistic Models
;
Oral Health
;
Oral Hygiene
;
Periodontal Diseases
;
Periodontitis*
;
Prevalence
;
Surveys and Questionnaires*
;
ROC Curve
;
Sensitivity and Specificity
;
Smoke
;
Smoking
5.Effects of Different Types of Ramen Sauce on Bovine Tooth Discoloration
Ha-Eun KIM ; Hee-Jung LIM ; Hyeon-Gyeong NOH ; Hye-Min BAE ; Hye-Young LEE ; Do-Seon LIM
Journal of Dental Hygiene Science 2023;23(1):20-28
Background:
This study aimed to determine the effect of ramen sauce on tooth tone changes over time, after selecting three different ramen colors from the ramens sold in the market, and applying the sauce to bovine teeth.
Methods:
Healthy bovine teeth were selected, and cutting discs were used to produce 60 specimens (5×5×3 mm), with 15 specimens distributed per county. Three types of ramen (buldak, chacharoni black bean sauce, and ottogi curry noodle) were used as the experimental group, and water was used as the negative control group. Tooth tone measurement was performed using a spectrophotometer (CM-700d) to measure the color before and after 1 (3 h 44 min), 2 (7 h 28 min), 3 (11 h 12 min), and 4 weeks (14 h 56 min). Analysis of the color tone change was performed using Statistical Package for the Social Sciences version 28.
Results:
In the experimental group, there was a significant color tone change before and after immersion. L* indicated the largest change in black bean sauce ramen, a* indicated buldak ramen, and b* indicated the largest change in curry ramen. The amount of color change (ΔE*) was the largest in curry ramen, followed by buldak and black bean sauce ramens. The results of the post-hoc analysis showed significant differences between all groups except buldak and black bean sauce ramens.
Conclusion
All three types of ramen revealed significant color change before and after immersion, and curry ramen showed the largest amount of color change among them.
6.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
Background:
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods:
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results:
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
7.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
Background:
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods:
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results:
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
8.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
Background:
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods:
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results:
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
9.Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status.
Jung Ho KIM ; Jeong Mo BAE ; Kyung Ju KIM ; Ye Young RHEE ; Younghoon KIM ; Nam Yun CHO ; Hye Seung LEE ; Mee Soo CHANG ; Gyeong Hoon KANG
Korean Journal of Pathology 2014;48(4):276-282
BACKGROUND: Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. METHODS: Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). RESULTS: Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). CONCLUSIONS: Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.
Cellular Structures
;
Colorectal Neoplasms*
;
DNA
;
DNA Mismatch Repair
;
Immunohistochemistry
;
Methylation
;
Microsatellite Instability
;
Microsatellite Repeats
;
Neoplasm Metastasis
;
Real-Time Polymerase Chain Reaction
10.Impact of amalgam removal on urinary mercury concentration in children: a pilot study.
Hye Jung JIN ; Eun Kyong KIM ; Gyeong Ji WOO ; Sang Uk IM ; Keun Bae SONG ; Youn Hee CHOI
Journal of Korean Academy of Oral Health 2013;37(4):194-199
OBJECTIVES: This pilot study aimed to evaluate the effect of dental amalgam, a restorative material, on children by measuring the mercury concentration in the urine as well as the number of teeth filled with dental amalgam. METHODS: Twenty children enrolled in grades 1-4 of two elementary schools in Daegu participated in this study. One trained dentist performed oral examinations and removed amalgam restorations from the teeth with a high and low speed handpiece. In order to measure the urinary mercury concentrations, urine samples were collected from all participants at baseline and immediately and 24 hours after removal of the dental amalgam restorations. RESULTS: The mean number of teeth from which the amalgam restorations was removed was 9.8 while the mean urinary mercury concentrations at baseline, immediately, and 24 hours after removal of dental amalgam restorations were 2.66, 2.76, and 2.76 microg/g creatinine, respectively. The mean urinary mercury concentration increased consistently after amalgam restoration removal. For those participants whose removed amalgamated surfaces were more than 11, the mean urinary mercury concentration immediately after amalgam restoration removal and 24 hours after removal increased consistently but showed no significant difference. CONCLUSIONS: This study demonstrated that dental amalgam restoration was related to urinary mercury concentration, and these findings present a possibility of mercury accumulation in the body. Therefore, we suggest future longitudinal studies to ensure the safety of children exposed to mercury by establishing criteria for amalgam removal.
Child*
;
Creatinine
;
Daegu
;
Dental Amalgam
;
Dentists
;
Diagnosis, Oral
;
Humans
;
Longitudinal Studies
;
Pilot Projects*
;
Tooth