Journal of Pathology and Translational Medicine

Original Article

Fatty acid synthetase expression in triple-negative breast cancer: Jin Hee Park, Hye Seung Han, So Dug Lim, Wook Youn Kim, Kyoung Sik Park, Young Bum Yoo, Seung Eun Lee, Wan-Seop Kim; J Pathol Transl Med. 2022;56(2):73-80. Published online January 21, 2022; DOI: https://doi.org/10.4132/jptm.2021.10.27

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Background
Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.
Methods
Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN.
Results
FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.
Conclusions
We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

Citations

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NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism
Nobuhiro Okada, Chihiro Ueki, Masahiro Shimazaki, Goki Tsujimoto, Susumu Kohno, Hayato Muranaka, Kiyotsugu Yoshikawa, Chiaki Takahashi
Communications Biology.2023;[Epub] CrossRef
Role of EGFR and FASN in breast cancer progression
Suchi Chaturvedi, Mainak Biswas, Sushabhan Sadhukhan, Avinash Sonawane
Journal of Cell Communication and Signaling.2023; 17(4): 1249. CrossRef
Bioinformatics Method Was Used to Analyze the Highly Expressed Gene FAM83A of Breast Cancer in Young Women
Yongzhe Tang, Hao Wang, Qi He, Yuanyuan Chen, Jie Wang, Fahd Abd Algalil
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NCAPH promotes proliferation as well as motility of breast cancer cells by activating the PI3K/AKT pathway
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Correspondence

Erratum: Correction of Acknowledgments. ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion: Sehun Kim, Hyung Kyu Park, Ho Young Jung, So-Young Lee, Kyueng-Whan Min, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Tae Sook Hwang, So Dug Lim; Korean J Pathol. 2013;47(5):503-503. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.503

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Brief Case Report

Neuroendocrine Dysplasia Combined in a Tubular Adenoma of Rectum: A Case Report: So-Young Lee, Dae-Yong Hwang, Tae Sook Hwang, Wan-Seop Kim, So Dug Lim, Wook Youn Kim, Se-Hun Kim, Hye Seung Han; Korean J Pathol. 2013;47(5):495-498. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.495

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Neuroendocrine cell micronests of the colon
Richard R. Pacheco, Maria Faraz, Hwajeong Lee
Human Pathology Reports.2022; 28: 300644. CrossRef
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Parag D Dabir, Rachel S van der Post, Iris D Nagtegaal
Histopathology.2021; 78(3): 348. CrossRef
Large cell neuroendocrine tumor of the gastrointestinal tract with concurrent tubular adenomas
Inayat GILL, Christienne SHAMS, Elisa QUIROZ, Subhashree M. KRISHNAN, Susanna GAIKAZIAN
Gazzetta Medica Italiana Archivio per le Scienze Mediche.2021;[Epub] CrossRef
Neuroendocrine tumor mixed with adenoma in rectum: a case report and literature review
Jiancong Hu, Xiaochuan Chen, Dezheng Lin, Zhaoliang Yu, Juan Li, Xuefeng Guo
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Case Study

Rhabdoid Colorectal Carcinomas: Reports of Two Cases: Sang Hwa Lee, Hyesil Seol, Wook Youn Kim, So Dug Lim, Wan Seop Kim, Tae Sook Hwang, Hye Seung Han; Korean J Pathol. 2013;47(4):372-377. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.372

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Abstract PDF

Rhabdoid colorectal carcinomas are very rare and only 10 cases have been previously reported. We report two cases of rhabdoid colorectal carcinoma, one arising in the sigmoid colon of a 62-year-old man and another in the rectum of an 83-year-old woman. In both cases, the patients had advanced tumors with lymph node metastases. The tumors mostly showed a diffuse arrangement with rhabdoid features and small glandular regions were combined. Transitional areas from the adenocarcinomas to the rhabdoid tumors were also noted. Adenocarcinoma cells were positive for mixed cytokeratin (CK), CK20 and epithelial membranous antigen (EMA), but focal positive for vimentin. The rhabdoid tumor cells were positive for mixed CK, but focal positive or negative for CK20 and EMA. In addition, they were diffusely positive for vimentin, but negative for desmin. The histological and immunohistologial findings of these two cases suggest that the rhabodid tumor cells originated from dedifferentiated adenocarcinomas.

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Poorly differentiated cecal adenocarcinoma showing prominent rhabdoid feature combined with appendiceal mucinous cystadenoma: A case report and review of the literature
IN-JU CHO, SUNG-SOO KIM, YOUNG-DON MIN, MUN-WHAN NOH, RAN HONG
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A Rare Case of Undifferentiated Carcinoma of the Colon with Rhabdoid Features: A Case Report and Review of the Literature
E. Moussaly, J. P. Atallah
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Case Report of Rhabdoid Colon Cancer and Review of Literature
Aparna Kalyan, Gurleen Pasricha, Dulabh Monga, Aatur Singhi, Nathan Bahary
Clinical Colorectal Cancer.2015; 14(1): e5. CrossRef
Malignant Rhabdoid Tumor of the Colon: A Case Report
Elena Romera Barba, Ainhoa Sánchez Pérez, Carlos Duque Pérez, José Antonio García Marcilla, José Luis Vázquez Rojas
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Original Article

ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion: Sehun Kim, Hyung Kyu Park, Ho Young Jung, So-Young Lee, Kyueng-Whan Min, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Tae Sook Hwang, So Dug Lim; Korean J Pathol. 2013;47(4):355-364. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.355

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Abstract PDF

Background

ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis.

Methods

Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics.

Results

The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%).

Conclusions

The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.

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Case Study

A Case of Multifocal Papillary Thyroid Carcinoma Consisting of One Encapsulated Follicular Variant with BRAF K601E Mutation and Three Conventional Types with BRAF V600E Mutation: Wook Youn Kim, Young Sin Ko, Tae Sook Hwang, Hye Seung Han, So Dug Lim, Wan Seop Kim, Seo Young Oh; Korean J Pathol. 2013;47(3):293-298. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.293

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Abstract PDF

Multifocal papillary thyroid carcinoma (mPTC) comprises about 20-30% of PTC. In mPTC, individual tumor foci can be identical or frequently composed of different histological types including follicular, solid, tall-cell or conventional patterns. We report a case of mPTC consisting of one encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) and three conventional PTCs in a 44-year-old woman. This case genetically demonstrates unique features including the simultaneous presence of the BRAF V600E (T1799A) mutation and the BRAF K601E (A1801G) mutation in conventional PTC and FVPTC, respectively.

Citations

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Original Articles

CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas.: Kyueng Whan Min, Young Ha Oh, Chan Kum Park, So Dug Lim, Wan Seop Kim; Korean J Pathol. 2011;45(6):589-595.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.589

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Abstract PDF: BACKGROUND
CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms.
METHODS
Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated.
RESULTS
A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041).
CONCLUSIONS
High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.

Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.: Young Sin Ko, Young Ha Oh, Chan Kum Park, Wook Youn Kim, Hye Seung Han, So Dug Lim, Tae Sook Hwang, Wan Seop Kim; Korean J Pathol. 2011;45(6):573-581.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.573

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Abstract PDF

BACKGROUND
Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity.
METHODS
We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x).
RESULTS
Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score.
CONCLUSIONS
The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.

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Clinical Usefulness of SurePath(TM) Liquid-based Cytology in Thyroid Fine Needle Aspiration: Comparison with the Conventional Smear in Diagnostic Efficacy and Applicability of BRAF Mutation Test.: Wook Youn Kim, Sang Hwa Lee, Young Sin Ko, So Dug Lim, Wan Seop Kim, Hye Seung Han, Hye Sil Seol, Seo Young Oh, Won Jin Moon, Tae Sook Hwang; Korean J Pathol. 2011;45(2):188-195.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.188

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Abstract PDF

BACKGROUND
Recently, liquid-based cytology (LBC) has been introduced as an alternative to the conventional smear (CS) technique in thyroid fine needle aspiration, due to its diagnostic convenience.
METHODS
We assessed 77 cases of thyroid fine needle aspiration using the SurePath(TM) method (SP) as LBC and CS via split-sample techniques. BRAF mutation tests were carried out via polymerase chain reaction and pyrosequencing immediately after diagnosis or a delay of more than one year.
RESULTS
In a comparison between SP and CS, the rate of concordance between SP and CS was as high as 84.4% (kappa value, 0.754). In comparison with histologic diagnosis, the overall sensitivity was 100% for both. The specificity was 62.5% for SP and 56.3% for CS. Relative to CS, papillary carcinomas on SP slides revealed more accentuated nuclear irregularities, nucleoli, and reduced nuclear size. In contrast to CS, the delayed BRAFV600E mutation test using SP slides after 1-2 years failed. The use of new primers amplifying shorter product size could help the delayed test achieve success.
CONCLUSIONS
Differences in the diagnostic efficacy of SP and CS were negligible. The failure of the delayed BRAF mutation test on the SP slides might be associated with DNA degradation.

Citations

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A Consideration of MGMT Gene Promotor Methylation Analysis for Glioblastoma Using Methylation-Specific Polymerase Chain Reaction and Pyrosequencing.: Sang Hwa Lee, Tae Sook Hwang, Young Cho Koh, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Young Sin Ko, So Dug Lim; Korean J Pathol. 2011;45(1):21-29.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.21

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Abstract PDF

BACKGROUND
O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is currently the most promising predictive marker for the outcome and benefit from temozolomide treatment in patients with glioblastoma, but there is no consensus on the analysis method for assessing the methylation status in the molecular diagnostic field. The objective of this study was to evaluate methylation-specific polymerase chain reaction (MSP) and pyrosequencing methods for assessing MGMT gene promotor methylation of glioblastoma as well as assessing the MGMT protein expression by immunohistochemistry.
METHODS
Twenty-seven cases of glioblastoma from the archives at the Department of Pathology Konkuk University Hospital were selected. MGMT promoter methylation was evaluated by MSP and the pyrosequencing methods. The MGMT expression was also measured at the protein level by immunohistochemistry.
RESULTS
Overall, MGMT hypermethylation was observed in 44.4% (12/27 cases) of the case of glioblastoma using either MSP or pyrosequencing. The concordant rate was 70.3% (19/27 cases) between MSP and pyrosequencing for MGMT methylation. There was no correlation between MGMT methylation and the protein expression. No significant differences in progression free survival and overall survival were seen between the methylated group and the unmethylated group by using either MSP or pyrosequencing. The status of the MGMT protein expression was correlated with progression free survival (p=0.026).
CONCLUSIONS
In this study the concordance rate between MSP and the pyrosequencing methods for assessing MGMT gene promotor methylation was relatively low for the cases of glioblastoma. This suggests that more reliable techniques for routine MGMT methylation study of glioblastoma remain to be developed because of quality control and assurance issues.

Citations

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Prognostic Role of Methylation Status of theMGMTPromoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients
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Journal of Korean Neurosurgical Society.2016; 59(1): 26. CrossRef
Distinct genetic alterations in pediatric glioblastomas
Sun-ju Byeon, Jae Kyung Myung, Se Hoon Kim, Seung-Ki Kim, Ji Hoon Phi, Sung-Hye Park
Child's Nervous System.2012; 28(7): 1025. CrossRef
MGMTGene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour
Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim
The Korean Journal of Pathology.2011; 45(5): 455. CrossRef

Case Report

Desmoplastic Small Round Cell Tumor with Ovarian Involvement: A Case Report.: Sang Hwa Lee, Wan Seop Kim, Ji Hoon Kim, Hye Seung Han, So Dug Lim, Sang Yoon Kim, Tae Sook Hwang; Korean J Pathol. 2009;43(2):185-188.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.185

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Abstract PDF: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm that preferentially involves the abdominal and pelvic cavities in relatively young males. We present a rare case of DSRCT arising in the ovary of a 16-year-old girl. During surgery, a 15 cm-sized huge mass was noted in the right ovary and wide spreading of the tumor was identified in the left ovary, uterine wall, and omentum and bowel wall. Histological investigation showed nests of small round cells with round nuclei and scanty eosinophilic cytoplasm accompanied with dense desmoplastic stroma. The immunohistochemistry showed that the tumor coexpressed epithelial, mesenchymal, and neuronal markers. The tumor cells ultrastructurally showed poorly developed cell junctions and occasionally showed intracytoplasmic aggregates of intermediate filaments. Molecular analysis of the tumor revealed chromosomal translocation t(11:22)(p13;q12) associated with the EWS-WT1 fusion protein. DSRCT should be included in the differential diagnosis of ovarian neoplasms in young patients.

Original Article

Glomerular Hypertrophy in Focal Segmental Glomerulosclerosis.: So Dug Lim, Tae Sook Kim, Hyun Soon Lee; Korean J Pathol. 1995;29(4):423-430.

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Abstract PDF: It is not clear whether glomerular hypertrophy is related to the pathogenesis of focal segmental glomerulosclerosis (FSGS). We analyzed renal biopsies from 20 adults with FSGS by morphometry, and the data were compared with those from age- and sex-matched patients with minimal lesion. Mean glomerular volume in the FSGS group was significantly larger than that in the minimal lesion group[(3.4 + 1.1 vs 2.5 0.5)x10(6) micrometer3, P<0.01]. The percentage of glomeruli with global and segmental sclerosis in FSGS group was significantly correlated with the mean glomerular volume (r=+0.66, P<0.001). Relative interstitial volume of renal cortex in the FSGS group was correlated with the serum creatinine concentration(r=+0.5, P<0.05). These results suggest that glomerular hypertrophy observed in our patients with FSGS was related to nephron loss caused by glomerulosclerosis. The interstitial fibrosis may lead to obliteration of postglomerular interstitial capillary network with secondary elevation of glomerular capillary pressure resulting in progressive loss of renal function.

Case Report

Chromomycosis of the Nasolacrimal Duct: Report of a case.: So Dug Lim, Ji Eun Kim, Kyu Rae Kim; Korean J Pathol. 1996;30(4):358-360.

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Abstract PDF: Chromomycosis is a chronic cutaneous fungal infection characterized by the presence of dark brown parasitic forms of fungi in biopsied tissues. It is usually resulted from the entry of the causative organism through a minor trauma, and therefore, most lesions are found on the exposed part of the body, such as limbs or face, and occurrence on the nasolacrimal duct is extremely rare. We report a case of chromomycosis of the right nasolacrimal duct, which was presented with clinical symptoms of nasolacrimal duct obstruction. The patient was a 40 year-old male who had had minor injuries on his left eye twice by paper and branches of the tree two months prior to epiphora in right eye. On dacryocystorhinostomy, right nasolacrimal duct was obstructed by pinkish brown mucoid ball. Microscopically, the mucoid ball revealed eosinophilic, amorphous, necrotic materials admixed with brown pigmented fungi. The organism showed characteristic dark brown, round, thick-walled, often septated, sclerotic bodies and brown pigmented long bead-like hyphae. The adjacent mucosa shows marked chronic nonspecific inflammation with fibrosis.

Original Articles

Application of the Revised Case Matrix Format to Tutorial in Pathology Teaching: An Interim Approach toward Problem-Based Learning under Traditional Curricular Structure.: Yong Il Kim, Chong Jai Kim, Gee Young Kim, Chul Woo Kim, Woo Ho Kim, Ja June Jang, Je Geun Chi, Gyeong Hoon Kang, Myeong Cherl Kook, Jung Sun Kim, Tae Sook Kim, Gee Young Kwon, So Dug Lim; Korean J Pathol. 1996;30(8):570-661.

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Abstract: This paper describes a student-centered case study program concerning the tumor pathology course for first year students in medical school under the traditional curricular structure. A traditional, discipline-oriented, lecture-laboratory approach was partly modified by introducing a tutuorial session using a modified case matrix format during the laboratory hours without altering the general scheme of the existing system. Small group tutorial sessions were set with the development of learning objectives emphasizing clinicopathologic reasoning and early exposure to future practical presentation which was followed by the large class session; each tutorial was supplied with a short clinical history, gross kodachrome slides, and microslides. The session for problem identification was replaced by proving a series of instructor-designed questions for both pathology and interdisciplinary correlation during which pedagogical implication was stressed the most. Student's active participation, development of self learning skill and vigorous teaching-learning process among students, and motivation/relevance for forthcoming pathology study were among the benefits conferred by this modification. We conclude that this approach is an interim step to meet the advantages of problem-based learning even in a traditional curricular structure.

Clinicopathologic Comparison between Autoimmune Cholangitis and Primary Biliary Cirrhosis.: Gyeong Hoon Kang, So Dug Lim, Eun Sil Yu, On Ja Kim, Geun Chan Lee, Neung Hwa Park, Dong Jin Suh; Korean J Pathol. 1998;32(2):115-124.

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Abstract PDF: Primary biliary cirrhosis (PBC) is characterized by histological findings of an immunoinflammatory destruction of small- and medium-sized bile ducts with progressive portal fibrosis, and the presence of anti-mitochondrial antibody (AMA) with a laboratory evidence of chronic cholestasis. The term "autoimmune cholangitis" (AIC) is used for a disease with the clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative AMA and positive anti-nuclear antibody (ANA) tests. Eight cases of AIC and ten cases of PBC were reviewed in order to determine whether there was any difference between two diseases in clinico-pathologic aspects. All of the patients were female and the mean ages of AIC and PBC patients were 48 and 47 years, respectively. ANA test was positive in six of ten PBC paients and their mean titer was lower than that of AIC patients. IgM level was significantly higher in PBC group than in AIC group. No significant difference was found between two groups with respect to biochemical and histopathological features. Since the only consistently distinguishing features between these two conditions are the autoantibody profile (AMA vs ANA) and immunoglobulin level (IgM), these two conditions might be part of a spectrum. PBC can be considered to be the same as AMA-positive AIC or alternatively AIC to be the same as AMA-negative PBC.

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