1.Prognostic Role and Clinical Association of Tumor-Infiltrating Lymphocyte, Programmed Death Ligand-1 Expression with Neutrophil-Lymphocyte Ratio in Locally Advanced Triple-Negative Breast Cancer
Jieun LEE ; Dong Min KIM ; Ahwon LEE
Cancer Research and Treatment 2019;51(2):649-663
PURPOSE: Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. RESULTS: Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post-NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). CONCLUSION: In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.
Breast Neoplasms
;
Diagnosis
;
Disease-Free Survival
;
Drug Therapy
;
Humans
;
Lymphocytes, Tumor-Infiltrating
;
Prognosis
;
Triple Negative Breast Neoplasms
2.Difference of Genome-Wide Copy Number Alterations between High-Grade Squamous Intraepithelial Lesions and Squamous Cell Carcinomas of the Uterine Cervix.
Bum Hee LEE ; Sangyoung ROH ; Yu Im KIM ; Ahwon LEE ; Su Young KIM
Korean Journal of Pathology 2012;46(2):123-130
BACKGROUND: About 10% of high-grade squamous intraepithelial lesions (HSILs) progress to invasive carcinomas within 2-10 years. By delineating the events that occur in the early stage of the invasion, the pathogenesis of cervical cancer could be better understood. This will also propose the possible methods for inhibiting the tumor invasion and improving the survival of patients. METHODS: We compared the genomic profiles between the HSIL and the invasive squamous cell carcinoma (SCC) using an array comparative genomic hybridization. Using recurrently altered genes, we performed a principal component analysis to see variation of samples in both groups. To find possibly affected pathways by altered genes, we analyzed genomic profiles with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and GOEAST software. RESULTS: We found 11q12.3 and 2p24.1 regions have recurrent copy number gains in both groups. 16p12-13 and 20q11-13 regions showed an increased copy number only in cases of HSIL. 1q25.3 and 3q23-29 regions showed copy number gains only in cases of SCC. Altered genes in the SCC group were related to the mitogen-activated protein kinase signaling pathway and the RNA transport. Altered genes in the HSIL group were related to the ubiquitin mediated proteolysis and cell adhesion molecules. CONCLUSIONS: Our results showed not only that gains in 11q12.3 and 2p24.1 were early events occurring in the premalignant lesions and then maintained in cases of SCC but also that gains in 1q25.3 and 3q23-29 were late events occurring after invasion in those of SCC.
Carcinoma, Squamous Cell
;
Cell Adhesion
;
Cervical Intraepithelial Neoplasia
;
Cervix Uteri
;
Coat Protein Complex I
;
Comparative Genomic Hybridization
;
DNA Copy Number Variations
;
Female
;
Gene Dosage
;
Genome
;
Principal Component Analysis
;
Protein Kinases
;
Proteolysis
;
RNA Transport
;
Ubiquitin
;
Uterine Cervical Neoplasms
3.Prognostic significance of syndecan-1 expression in cervical cancers.
Yu Im KIM ; Ahwon LEE ; Bum Hee LEE ; Su Young KIM
Journal of Gynecologic Oncology 2011;22(3):161-167
OBJECTIVE: Syndecans are reported to have variable expression in several solid tumors and blood cancers. The cause provoking altered expression of syndecans is not known to date. We studied copy number status of syndecan-1 (SDC1) and significance of SDC1 gene product (syndecan-1, SDC1) expression in cervical cancers. METHODS: Using 121 cases of cervical cancer tissues, we screened SDC1 expression pattern using immunohistochemistry. We analyzed the relationship between SDC1 expression and clinicopathological parameters. To find possible causes of the expression change, we exploited interphase fluorescent in situ hybridization to screen copy number alteration of SDC1. RESULTS: Among 121 cases, 101 (83.5%) were positive and 20 (16.4%) were negative for SDC1. Among the parameters, age, histological type, and grade were significantly associated with SDC1 expression (p<0.05). Strong SDC1 expression in the cytoplasm showed better patient survival (p=0.02). In multivariate regression model, grade and SDC1 expression were independent prognostic factors (p<0.05). SDC1 in cervical cancers did not show copy number alteration. CONCLUSION: Strong SDC1 expression in the cytoplasm of tumor cells predicts better patient survival. The change of SDC1 expression in cervical cancers is not caused by copy number alteration of the gene.
Coat Protein Complex I
;
Cytoplasm
;
DNA Copy Number Variations
;
Gene Expression
;
Humans
;
Immunohistochemistry
;
In Situ Hybridization, Fluorescence
;
Interphase
;
Syndecan-1
;
Syndecans
;
Uterine Cervical Neoplasms
4.Early Prediction of Response to Neoadjuvant Chemotherapy Using Dynamic Contrast-Enhanced MRI and Ultrasound in Breast Cancer.
Yunju KIM ; Sung Hun KIM ; Byung Joo SONG ; Bong Joo KANG ; Kwang il YIM ; Ahwon LEE ; Yoonho NAM
Korean Journal of Radiology 2018;19(4):682-691
OBJECTIVE: To determine the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and DCE ultrasound (DCE-US) for predicting response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: This Institutional Review Board-approved prospective study was performed between 2014 and 2016. Thirty-nine women with breast cancer underwent DCE-US and DCE-MRI before the NAC, follow-up DCE-US after the first cycle of NAC, and follow-up DCE-MRI after the second cycle of NAC. DCE-MRI parameters (transfer constant [Ktrans], reverse constant [kep], and leakage space [Ve]) were assessed with histograms. From DCE-US, peak-enhancement, the area under the curve, wash-in rate, wash-out rate, time to peak, and rise time (RT) were obtained. After surgery, all the imaging parameters and their changes were compared with histopathologic response using the Miller-Payne Grading (MPG) system. Data from minor and good responders were compared using Wilcoxon rank sum test, chi-square test, or Fisher's exact test. Receiver operating characteristic curve analysis was used for assessing diagnostic performance to predict good response. RESULTS: Twelve patients (30.8%) showed a good response (MPG 4 or 5) and 27 (69.2%) showed a minor response (MPG 1–3). The mean, 25th, 50th, and 75th percentiles of Ktrans and Kep of post-NAC DCE-MRI differed between the two groups. These parameters showed fair to good diagnostic performance for the prediction of response to NAC (AUC 0.76–0.81, p ≤ 0.007). Among DCE-US parameters, the percentage change in RT showed fair prediction (AUC 0.71, p = 0.023). CONCLUSION: Quantitative analysis of DCE-MRI and DCE-US was helpful for early prediction of response to NAC.
Breast Neoplasms*
;
Breast*
;
Drug Therapy*
;
Female
;
Follow-Up Studies
;
Humans
;
Magnetic Resonance Imaging*
;
Prospective Studies
;
ROC Curve
;
Ultrasonography*
5.Metastasis of Rhabdomyosarcoma to the Male Breast: a Case Report with Magnetic Resonance Imaging Findings
Myeongjong KIM ; Bong Joo KANG ; Ga Eun PARK ; Sung Hun KIM ; Jeongmin LEE ; Ahwon LEE
Investigative Magnetic Resonance Imaging 2019;23(1):75-80
Metastasis of rhabdomysarcoma to the breast is a very rare manifestation in adult males. Herein, we report a case of metastasis from embryonal rhabdomyosarcoma in the left hypothenar muscle that presented as a breast mass in a 38-year-old man, who four months later expired because of multiple bone metastases related to pancytopenia. We describe the various imaging findings, including mammograms, ultrasonography, computerized tomography (CT), positron emission tomography-computed tomography (PET-CT), and magnetic resonance imaging (MRI) of this rare disease. The various imaging findings of this lesion could be helpful for future diagnosis of male breast lesions.
Adult
;
Breast
;
Diagnosis
;
Electrons
;
Humans
;
Magnetic Resonance Imaging
;
Male
;
Neoplasm Metastasis
;
Pancytopenia
;
Rare Diseases
;
Rhabdomyosarcoma
;
Rhabdomyosarcoma, Embryonal
;
Ultrasonography
6.Primary Diffuse Large B-cell Lymphoma of the Prostate: A Case Report.
Dong chul KIM ; Gyeongsin PARK ; Ahwon LEE ; Kyungja HAN ; Chang Suk KANG
Korean Journal of Pathology 2003;37(6):432-434
Primary lymphomas of the prostate are extremely rare and can mimic other more common prostatic lesions clinically. We report a case of primary diffuse large B-cell lymphoma of the prostate in an 81-year-old man. The patient presented with voiding difficulty as an initial symptom and enlargement of the prostate on rectal digital examination. Transurethral prostatic resection was performed. On microscopic examination, atypical lymphoid cells infiltrated and replaced the prostatic parenchyma. The tumor cells had large nuclei with irregular nuclear membrane and vesicular clumped chromatin. Nucleoli were not distinct and the cells had scanty cytoplasm. Immunohistochemically, the tumor cells were immunoreactive for CD20 and CD79a but not reactive for CD5, BCL-2 and BCL-6. Histopathological diagnosis was diffuse large B-cell lymphoma of the prostate. The patient received 5 cycles of chemotherapy after histologic diagnosis but died from pulmonary and scrotal metastases 6 months later.
Aged, 80 and over
;
B-Lymphocytes*
;
Chromatin
;
Cytoplasm
;
Diagnosis
;
Drug Therapy
;
Humans
;
Lymphocytes
;
Lymphoma
;
Lymphoma, B-Cell*
;
Neoplasm Metastasis
;
Nuclear Envelope
;
Prostate*
7.Prognostic Significance of P53, BCL-2 and PCNA in Diffuse Large B-Cell Lymphoma: Correlation with International Prognostic Index.
Dong chul KIM ; Gyeongsin PARK ; Ahwon LEE ; Kyo Young LEE ; Sang In SHIM ; Chang Suk KANG
Korean Journal of Pathology 2003;37(6):407-412
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents a diverse spectrum of clinical presentation, morphology, and genetic and molecular alterations, and shows variable prognoses and responses to therapy. The International Prognosis Index (IPI) is widely used to predict prognosis but is not precise. METHODS: Thirty-nine cases of DLBCL were classified into low- and high-risk groups according to IPI and were analyzed for their p53, BCL-2, BCL-6 and PCNA expression profile by immunohistochemical staining and overall survival rate. RESULTS: The mean age of the 39 patients, 23 males and 16 females, was 52.6 years. There were 23 cases (59.0%) in the low-risk group and 16 (41.0%) in the high-risk group. p53, BCL-2, BCL-6 and PCNA expression was higher in the high-risk group than in the low-risk group, but only the differences in p53 and BCL-2 expression were statistically significant (p < 0.05). CONCLUSION: The p53 and BCL-2 protein expression in DLBCL may supplement IPI in predicting the prognosis of DLBCL patients.
B-Lymphocytes*
;
Female
;
Humans
;
Lymphoma, B-Cell*
;
Lymphoma, Large B-Cell, Diffuse
;
Male
;
Prognosis
;
Proliferating Cell Nuclear Antigen*
;
Survival Rate
8.Invasive Ductal Carcinoma Arising in a Recurrent Malignant Phyllodes Tumor: A Case Report.
Ahwon LEE ; Gyeongsin PARK ; Kyo Young LEE ; Chang Suk KANG ; Byung Kee KIM ; Sang In SHIM
Korean Journal of Pathology 2005;39(2):134-136
We report here on a case of invasive ductal carcinoma arising in a recurrent malignant phyllodes tumor. The patient was a 33-year-old woman who presented with a left breast mass, and an excision was then performed. The mass, measuring 7.0 x 4.0 cm in size, was relatively well demarcated with a nodular contour and showed pale gray and solid cut surface with clefts on it. Histologically, the mass mainly consisted of stromal components that were characterized by high cellularity, marked nuclear atypism and brisk mitosis. The sparse glandular components were leaf-like in shape and lined by bland ductal epithelium without any nuclear atypism. Sixteen months later, the patient revisited our hospital with a recurrent mass, and underwent total mastectomy. The recurrent mass contained foci of definite invasive ductal carcinoma in the background of malignant phyllodes tumor, which was identical to the primary mass. This case demonstrates that it is possible that an invasive ductal carcinoma might arise within, at least with, a recurrent malignant phyllodes tumor.
Adult
;
Breast
;
Carcinoma, Ductal*
;
Epithelium
;
Female
;
Humans
;
Mastectomy, Simple
;
Mitosis
;
Phyllodes Tumor*
9.Imaging Findings of Metastatic Breast Malignant Fibrous Histiocytoma: A Case Report.
Hyun Sil LEE ; Bong Joo KANG ; Sung Hun KIM ; Ahwon LEE
Journal of the Korean Society of Magnetic Resonance in Medicine 2013;17(4):316-320
Malignant fibrous histiocytoma (MFH) of the breast is extremely rare and most of the previous reports were focused on the clinicopathological features of breast MFH, so analysis of its imaging findings have been limited. We report a case of MFH involving left breast and left axilla, metastasized from known MFH of left forearm, with focusing on imaging findings based on radiologic evaluation of the breast including mammography, ultrasound and breast MRI.
Axilla
;
Breast*
;
Forearm
;
Histiocytoma, Malignant Fibrous*
;
Magnetic Resonance Imaging
;
Ultrasonography, Mammary
10.Immune-Checkpoint-Inhibitor-Induced Severe Autoimmune Encephalitis Treated by Steroid and Intravenous Immunoglobulin
Ahwon KIM ; Bhumsuk KEAM ; Hyeon CHEUN ; Soon Tae LEE ; Hyung Seok GOOK ; Moon Ku HAN
Journal of Clinical Neurology 2019;15(2):259-261
No abstract available.
Encephalitis
;
Immunoglobulins