Journal of Pathology and Translational Medicine

Review

Exploring histological predictive biomarkers for immune checkpoint inhibitor therapy response in non–small cell lung cancer: Uiju Cho, Soyoung Im, Hyung Soon Park; J Pathol Transl Med. 2024;58(2):49-58. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.31

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Abstract PDF: Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

Original Articles

Microtubule-Associated Protein Tau, α-Tubulin and βIII-Tubulin Expression in Breast Cancer: Soyoung Im, Changyoung Yoo, Ji-Han Jung, Ye-Won Jeon, Young Jin Suh, Youn Soo Lee, Hyun Joo Choi; Korean J Pathol. 2013;47(6):534-540. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.534

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Abstract PDF

Background

The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment.

Methods

Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival.

Results

Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049).

Conclusions

Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

Citations

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Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival: Soyoung Im, Hyun Joo Choi, Changyoung Yoo, Ji-Han Jung, Ye-Won Jeon, Young Jin Suh, Chang Suk Kang; Korean J Pathol. 2013;47(2):116-123. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.116

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Abstract PDF

Background

The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established.

Methods

Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically.

Results

The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012).

Conclusions

Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

Citations

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Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy: Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh; Korean J Pathol. 2013;47(1):61-66. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.61

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Abstract PDF

Background

This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC.

Methods

Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case.

Results

Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimoto's thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%.

Conclusions

This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

Citations

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Prevalence and Predictors of Malignancy in Contralateral Thyroid Lobe in Patients Undergoing Completion Thyroidectomy
Pradipta Kumar Parida, Siddhartha Pradhan, Chapity Preetam, Pradeep Pradhan, Dillip Kumar Samal, Saurav Sarkar
Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S2): 2053. CrossRef
Ultrasonographic and cytologic assessments of follicular neoplasms of the thyroid: Predictive features differentiating follicular carcinoma from follicular adenoma
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2019 Practice guidelines for thyroid core needle biopsy: a report of the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association
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Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses
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Core needle biopsy of thyroid nodules: outcomes and safety from a large single-center single-operator study
Jooae Choe, Jung Hwan Baek, Hye Sun Park, Young Jun Choi, Jeong Hyun Lee
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Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions
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Galina Chernaya, Nina Mikhno, Tatiana Khabalova, Svetlana Svyatchenko, Lyudmila Mostovich, Sergey Shevchenko, Lyudmila Gulyaeva
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The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
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Core Needle Biopsy of the Thyroid: 2016 Consensus Statement and Recommendations from Korean Society of Thyroid Radiology
Dong Gyu Na, Jung Hwan Baek, So Lyung Jung, Ji-hoon Kim, Jin Yong Sung, Kyu Sun Kim, Jeong Hyun Lee, Jung Hee Shin, Yoon Jung Choi, Eun Ju Ha, Hyun Kyung Lim, Soo Jin Kim, Soo Yeon Hahn, Kwang Hwi Lee, Young Jun Choi, Inyoung Youn, Young Joong Kim, Hye Sh
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Case Reports

A Cutaneous Myoepithelial Carcinoma Arising in a Papillary Eccrine Adenoma.: Ji Han Jung, Soyoung Im, Seok Jin Kang, Gyong Moon Kim, Ki Taik Han, Jin Young Yoo, Chang Suk Kang; Korean J Pathol. 2011;45(6):644-649.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.644

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Abstract PDF

Cutaneous myoepithelial neoplasms and papillary eccrine adenomas (PEA) are rare conditions. Malignant tumors within a PEA are even rarer, with only one case reported to date. Herein, we present an extremely rare case of a cutaneous myoepithelial carcinoma arising in a PEA in a 70-year-old man presenting a solid mass in the left buttock. Histopathologically, most of the resected tumor revealed features consistent with the diagnosis of PEA. Some small nests and nodules were intermixed with the PEA and were present adjacent to the PEA. The tumor cells of nests and nodules showed ovoid to spindle shaped nuclei and slightly eosinophilic cytoplasm. Immunohistochemically, they were positive for both epithelial and myogenic markers, consistent with myoepithelioma. An inguinal lymph node with a metastatic lesion showed the same findings of myoepithelioma despite inconspicuous atypia. Our case showed malignant transformation of the myoepithelial cells at the outermost layers of the PEA.

Citations

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Papillary eccrine adenoma associated with syringocystadenoma papilliferum
Neha Meena, PrafullaKumar Sharma, Sawan Kumar, Minakshi Bhardwaj
Indian Journal of Dermatology, Venereology and Leprology.2018; 84(3): 322. CrossRef
Pleural fluid metastases of myoepithelial carcinoma: A case report and review of the literature
Alicia Calderon Bhambra, Yanhong Zhang, Eric C. Huang, John Bishop, Mahan Matin, Alaa Afify
CytoJournal.2016; 13: 13. CrossRef

Malignant Fibrous Histiocytoma Arising in a Mature Cystic Teratoma of the Ovary: A Case Report.: Soyoung Im, Sun Mi Lee, Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2010;44(3):322-325.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.322

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Abstract PDF: A 50-year-old female patient presented with anorexia and weight loss. Pelvic computed tomography revealed a 12.5 x 7.3 cm heterogeneous mass in the left ovary. About 30% of the tumor was occupied by a mature cystic teratoma. The remaining solid portion was composed of fibrous and histiocytic elements, arranged in storiform patterns admixed with bizarre giant cells. The mitotic index was 8 per 10 high power fields, including atypical mitoses. The only immunopositivity was for vimentin. The tumor was diagnosed as a malignant fibrous histiocytoma arising in a mature cystic teratoma. To the best of our knowledge, this is only the third such case in the English language literature.

Original Article

Comparison of Various Detection Methods of Mycobacterium Species in Formalin-Fixed Paraffin-Embedded Tissue with Chronic Granulomatous Inflammation.: Hyun Seung Lee, Hyoungnam Lee, Soyoung Im, Yun Su Lee, Kyo Young Lee, Yeong Jin Choi; Korean J Pathol. 2010;44(3):259-266.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.259

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Abstract PDF

BACKGROUND
To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR).
METHODS
We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases.
RESULTS
Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%).
CONCLUSIONS
RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.

Citations

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Clinical Usefulness of PCR for Differential Diagnosis of Tuberculosis and Nontuberculous Mycobacterial Infection in Paraffin-Embedded Lung Tissues
Yo Na Kim, Kyoung Min Kim, Ha Na Choi, Ju Hyung Lee, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung
The Journal of Molecular Diagnostics.2015; 17(5): 597. CrossRef
Usefulness of PCR to Mycobacterium Tuberculous and Nontuberculous Mycobacteria from Paraffin-embedded Tissues
Yeon-Il Choi, Hye-Young Kim
Korean Journal of Clinical Laboratory Science.2014; 46(2): 47. CrossRef

Case Report

Complex Bronchopulmonary Foregut Malformation: Extralobar Pulmonary Sequestration Communicating with an Esophageal Duplication Cyst: A Case Report.: Soyoung Im, Sun Mi Lee, Ji Han Jung, Jinyoung Yoo, Kyu Do Cho, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2010;44(2):207-210.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.207

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Abstract PDF

We report here on a case of a rare, complex bronchopulmonary foregut malformation (BPFM) that was composed of an extralobar pulmonary sequestration communicating with an esophageal duplication cyst. A 33-year-old female presented with an incidentally detected chest mass. The computed tomography revealed a 7.5 x 4.0 cm sized heterogeneous, solid and cystic lesion in the right superior mediastinum. Surgical resection demonstrated the solid portion to be isolated lung tissue invested in its own pleura. A unilocular cyst was communicating with the bronchus of the sequestrated lung, and microscopically the cyst was lined by squamous epithelium overlying the thick layers of smooth muscle. This case is important for understanding the spectrum of BPFMs and for differentiating a mediastinal mass, especially one at the unusual location.

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Original Article

Alteration of G1/S Cell Cycle Regulatory Proteins in Carcinogenesis of Cutaneous Squamous Cell Carcinomas.: Soyoung Im, Changyoung Yoo, Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2009;43(6):542-549.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.542

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Abstract PDF

BACKGROUND
Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. METHODS: We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen's disease (BD; n=37), keratoacanthoma (KA; n=23), and squamous cell carcinoma (SCC; n=22). RESULTS: The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. CONCLUSIONS: The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.

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Expression of pRb, p53, p16 and Cyclin D1 and Their Clinical Implications in Urothelial Carcinoma
Kyungji Lee, Eun Sun Jung, Young-Jin Choi, Kyo Young Lee, Ahwon Lee
Journal of Korean Medical Science.2010; 25(10): 1449. CrossRef

Case Report

The Cytologic Features of Chronic Myelogenous Leukemia and Its Lymphoid Blast Phase in Body Fluid: A Case Report.: Soyoung Im, Changyoung Yoo, Youn Soo Lee, Chang Suk Kang, Sang In Sim, Kyo Young Lee; Korean J Pathol. 2009;43(2):189-194.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.189

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Abstract PDF: Although chronic myelogenous leukemia (CML) may be involved in any part of the body, infiltration of the body fluid has rarely reported in the literature. Here we report on a 35 year-old male patient who was diagnosed chronic myelogenous leukemia ten years previously and he received allogenic hematopoietic stem cell transplantation. He then presented with left knee pain eight years after the initial diagnosis. MRI revealed a soft tissue mass at the distal femur. Cytology of the joint fluid revealed myeloblasts, promyelocytes, eosinophilic myelocytes, band neutrophils, megakaryocytes and orthochromatic erythroblasts, which was all consistent with leukemic infiltration of the knee joint fluid. The immunohistochemistry was positive for CD34, CD117 and myeloperoxidase (MPO). Despite that the patient underwent radiation therapy, MRI revealed growth of the mass, and ten months later, the lymphoid blast phase of CML was confirmed after biopsy. The patient received an above knee amputation. Five months later, multiple masses were revealed on PET-CT at the left iliopsoas muscle, abdominal wall and bones. Bilateral pleural effusion occurred shortly after this. Cytologic evaluation of the pleural fluid also revealed blast-like cells, and histologic evaluation of the abdominal mass confirmed the lymphoid blast phase of CML with positivity for CD3, UCHL-1, CD34 and CD117, but negativity for MPO.

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