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Letter To The Editor
Response to comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
J Pathol Transl Med. 2024;58(1):43-44.   Published online January 10, 2024
DOI: https://doi.org/10.4132/jptm.2023.12.04
  • 849 View
  • 33 Download
PDF
Review
A stepwise approach to fine needle aspiration cytology of lymph nodes
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
J Pathol Transl Med. 2023;57(4):196-207.   Published online July 11, 2023
DOI: https://doi.org/10.4132/jptm.2023.06.12
  • 7,771 View
  • 657 Download
  • 1 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary Material
The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Citations

Citations to this article as recorded by  
  • Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma
    Joshua J. X. Li, Gary M. Tse
    Cytopathology.2024; 35(2): 218.     CrossRef
  • Response to comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
    Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
    Journal of Pathology and Translational Medicine.2024; 58(1): 43.     CrossRef
  • Comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
    Elisabetta Maffei, Valeria Ciliberti, Pio Zeppa, Alessandro Caputo
    Journal of Pathology and Translational Medicine.2024; 58(1): 40.     CrossRef
Original Article
A machine-learning expert-supporting system for diagnosis prediction of lymphoid neoplasms using a probabilistic decision-tree algorithm and immunohistochemistry profile database
Yosep Chong, Ji Young Lee, Yejin Kim, Jingyun Choi, Hwanjo Yu, Gyeongsin Park, Mee Yon Cho, Nishant Thakur
J Pathol Transl Med. 2020;54(6):462-470.   Published online August 31, 2020
DOI: https://doi.org/10.4132/jptm.2020.07.11
  • 4,060 View
  • 106 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary Material
Background
Immunohistochemistry (IHC) has played an essential role in the diagnosis of hematolymphoid neoplasms. However, IHC interpretations can be challenging in daily practice, and exponentially expanding volumes of IHC data are making the task increasingly difficult. We therefore developed a machine-learning expert-supporting system for diagnosing lymphoid neoplasms.
Methods
A probabilistic decision-tree algorithm based on the Bayesian theorem was used to develop mobile application software for iOS and Android platforms. We tested the software with real data from 602 training and 392 validation cases of lymphoid neoplasms and compared the precision hit rates between the training and validation datasets.
Results
IHC expression data for 150 lymphoid neoplasms and 584 antibodies was gathered. The precision hit rates of 94.7% in the training data and 95.7% in the validation data for lymphomas were not statistically significant. Results in most B-cell lymphomas were excellent, and generally equivalent performance was seen in T-cell lymphomas. The primary reasons for lack of precision were atypical IHC profiles for certain cases (e.g., CD15-negative Hodgkin lymphoma), a lack of disease-specific markers, and overlapping IHC profiles of similar diseases.
Conclusions
Application of the machine-learning algorithm to diagnosis precision produced acceptable hit rates in training and validation datasets. Because of the lack of origin- or disease- specific markers in differential diagnosis, contextual information such as clinical and histological features should be taken into account to make proper use of this system in the pathologic decision-making process.

Citations

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  • Validation of a Machine Learning Expert Supporting System, ImmunoGenius, Using Immunohistochemistry Results of 3000 Patients with Lymphoid Neoplasms
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    Diagnostics.2023; 13(7): 1308.     CrossRef
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    Nishant Thakur, Mohammad Rizwan Alam, Jamshid Abdul-Ghafar, Yosep Chong
    Cancers.2022; 14(14): 3529.     CrossRef
  • Diagnosis prediction of tumours of unknown origin using ImmunoGenius, a machine learning-based expert system for immunohistochemistry profile interpretation
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    Diagnostic Pathology.2021;[Epub]     CrossRef
Review
Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification
Hyun-Jung Kim, Young Hyeh Ko, Ji Eun Kim, Seung-Sook Lee, Hyekyung Lee, Gyeongsin Park, Jin Ho Paik, Hee Jeong Cha, Yoo-Duk Choi, Jae Ho Han, Jooryung Huh
J Pathol Transl Med. 2017;51(4):352-358.   Published online June 5, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.15
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  • 1,036 Download
  • 63 Web of Science
  • 60 Crossref
AbstractAbstract PDF
Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

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Original Articles
Histologic Disorderliness in the Arrangement of Tumor Cells as an Objective Measure of Tumor Differentiation
Sungwook Suh, Gyeongsin Park, Young Sub Lee, Yosep Chong, Youn Soo Lee, Yeong Jin Choi
Korean J Pathol. 2014;48(5):339-345.   Published online October 27, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.339
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AbstractAbstract PDF
Background: Inter-observer and intra-observer variation in histologic tumor grading are well documented. To determine whether histologic disorderliness in the arrangement of tumor cells may serve as an objective criterion for grading, we tested the hypothesis the degree of disorderliness is related to the degree of tumor differentiation on which tumor grading is primarily based. Methods: Borrowing from the statistical thermodynamic definition of entropy, we defined a novel mathematical formula to compute the relative degree of histologic disorderliness of tumor cells. We then analyzed a total of 51 photomicrographs of normal colorectal mucosa and colorectal adenocarcinoma with varying degrees of differentiation using our formula. Results: A one-way analysis of variance followed by post hoc pairwise comparisons using Bonferroni correction indicated that the mean disorderliness score was the lowest for the normal colorectal mucosa and increased with decreasing tumor differentiation. Conclusions: Disorderliness, a pathologic feature of malignant tumors that originate from highly organized structures is useful as an objective tumor grading proxy in the field of digital pathology.
Mesenchymal Stromal Cells Promote Tumor Progression in Fibrosarcoma and Gastric Cancer Cells
Byunghoo Song, Bokyung Kim, Se-Ha Choi, Kyo Young Song, Yang-Guk Chung, Youn-Soo Lee, Gyeongsin Park
Korean J Pathol. 2014;48(3):217-224.   Published online June 26, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.217
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AbstractAbstract PDF
Background

Extensive evidence has accumulated regarding the role of mesenchymal stromal cells (MSCs) in tumor progression, but the exact effects and mechanisms underlying this role remain unclear. We investigated the effects of MSC-associated tumor progression in MSC-sarcoma models and a gastric cancer metastatic model.

Methods

We conducted an in vitro growth kinetics assay and an in vivo tumor progression assay for sarcoma cells and gastric cancer cells in the presence or absence of MSCs.

Results

MSC-cocultured human fibrosarcoma cells (HT1080) showed accelerated growth compared with HT1080 alone (79- vs 37-fold change, p<.050). For HT1080, human MSC-coinjected tumors showed significantly greater and highly infiltrative growth compared to those of HT1080 alone (p=.035). For mouse fibrosarcoma cells (WEHI164), mouse MSC-coinjected tumors had greater volume than those of WEHI164 alone (p=.141). For rat sarcoma cells (RR1022), rat MSC-coinjected tumors exhibited greater volume and infiltrative growth than those of RR1022 alone (p=.050). For human gastric cancer cells (5FU), tumors of 5FU alone were compact, nodular in shape, and expansile with good demarcation and no definite lung metastatic nodules, whereas tumors grown in the presence of human MSCs showed highly desmoplastic and infiltrative growth and multiple lung metastasis.

Conclusions

We observed morphological evidence for MSC-associated tumor progression of fibrosarcomas and gastric cancer cells.

Citations

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    Asulin Masha, Ghedalia-Peled Noa Ben, Erez Ifat Cohen, Ventura Yvonne, Vago Razi
    Open Journal of Orthopedics and Rheumatology.2020; : 037.     CrossRef
  • Mesenchymal stem-cell therapy for perianal fistulas in Crohn’s disease: a systematic review and meta-analysis
    F. Cheng, Z. Huang, Z. Li
    Techniques in Coloproctology.2019; 23(7): 613.     CrossRef
  • Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery
    PAOLA A. FILOMENO, KYUNG-PHIL KIM, NARA YOON, IRAN RASHEDI, VICTOR DAYAN, RITA A. KANDEL, XING-HUA WANG, TANIA C. FELIZARDO, ELLIOT BERINSTEIN, SALOMEH JELVEH, ANDREA FILOMENO, JEFFREY A. MEDIN, PETER C. FERGUSON, ARMAND KEATING
    Cytotherapy.2018; 20(8): 1001.     CrossRef
  • Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases
    C. Grégoire, C. Lechanteur, A. Briquet, É. Baudoux, F. Baron, E. Louis, Y. Beguin
    Alimentary Pharmacology & Therapeutics.2017; 45(2): 205.     CrossRef
  • Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice
    Lin Song, Xin Zhou, Hong-Jun Jia, Mei Du, Jin-Ling Zhang, Liang Li
    Asian Pacific Journal of Tropical Medicine.2016; 9(8): 796.     CrossRef
  • BMP9 inhibits the growth and migration of lung adenocarcinoma A549 cells in a bone marrow stromal cell-derived microenvironment through the MAPK/ERK and NF-κB pathways
    JING WANG, YAGUANG WENG, MINGHAO ZHANG, YA LI, MENGTIAN FAN, YANGLIU GUO, YANTING SUN, WANG LI, QIONG SHI
    Oncology Reports.2016; 36(1): 410.     CrossRef
  • Comparative proteomic analysis of fibrosarcoma and skin fibroblast cell lines
    Ogunc Meral, Hamdi Uysal
    Tumor Biology.2015; 36(2): 561.     CrossRef
  • Involvement of Wnt/β-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma
    Weiwei Wang, Wei Zhong, Jiahui Yuan, Congcong Yan, Shaoping Hu, Yinping Tong, Yubin Mao, Tianhui Hu, Bing Zhang, Gang Song
    Oncotarget.2015; 6(39): 42276.     CrossRef
Detection Limit of Monoclonal B-Cells Using Multiplex PCR and Laser-Induced Fluorescence Capillary Electrophoresis.
Sung Hak Lee, Yeonsook Moon, Byunghoo Song, Hyung Nam Lee, Ahwon Lee, Eun Sun Jung, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang, Gyeongsin Park
Korean J Pathol. 2011;45(6):582-588.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.582
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AbstractAbstract PDF
BACKGROUND
The identification of monoclonality has been widely used for making diagnoses of lymphoproliferative lesions. Awareness of the sensitivity and detection limit of the technique used would be important for the data to be convincing.
METHODS
We investigated the minimum requirement of cells and sensitivity of gel electrophoresis (GE) and laser-induced fluorescence capillary electrophoresis (LFCE) for identifying IgH gene rearrangement using BIOMED-2 protocols. DNA extracted from Raji cells were diluted serially with peripheral blood mononuclear cells (PBMNCs) DNA. DNA from mixtures of diffuse large B-cell lymphoma (DLBCL) and reactive lymph nodes were also serially diluted.
RESULTS
For Raji cells, the detection limit was 62 and 16 cell-equivalents for GE and LFCE, respectively. In the condition with PBMNCs mixture, 2.5% and 1.25% of clonal cells was the minimum requirement for GE and LFCE, respectively. In 23% of DLBCL cells in tissue section, the detection limit was 120 and 12 cell-equivalents for GE and LFCE, respectively. In 3.2% of DLBCL cells, that was 1,200 and 120 cell-equivalents for GE and LFCE, respectively.
CONCLUSIONS
These results show that LFCE method is more sensitive than GE and the sensitivity of clonality detection can be influenced by the amount of admixed normal lymphoid cells.

Citations

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  • Molecular pathology diagnosis of diffuse large B cell lymphoma using BIOMED-2 clonal gene rearrangements
    Saeid Ghorbian
    Annals of Diagnostic Pathology.2017; 29: 28.     CrossRef
The Usefulness of p16INK4a Immunocytochemical Staining in ASC-H Patients.
Kwang Il Yim, Yeo Ju Kang, Tae Eun Kim, Gyeongsin Park, Eun Sun Jung, Yeong Jin Choi, Kyo Young Lee, Chang Seok Kang, Ahwon Lee
Korean J Pathol. 2011;45(3):290-295.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.290
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AbstractAbstract PDF
BACKGROUND
The grey zone of cervical cytology, and in particular atypical squamous cells, cannot exclude HSIL (ASC-H) causes diagnostic difficulties and increases medical expenses. We analyzed p16INK4a expression in ASC-H liquid-based cytology specimens (LBCS) to develop more effective methods for the management of ASC-H patients.
METHODS
We carried out p16INK4a immunostaining with 57 LBCS of ASC-H diagnostic categories, all of which were histologically cofirmed and 43 cases of which were compared with the results of a human papillomavirus (HPV) chip test.
RESULTS
p16INK4a immunostaining with ASC-H LBCS was positive in 20% (3/15) of cervicitis, 25.0% (3/12) of tissue-low-grade squamous intraepithelial lesion, 75.0% (18/24) of tissue-high grade squamous intraepithelial lesion (HSIL), and 100% (6/6) of invasive cancer cases. The positivity of p16INK4a in LBCS was correlated with higher grade of histologic diagnosis (r=0.578, p=0.000). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16INK4a immunostaining for the prediction of tissue-HSIL+ were 80.0%, 77.8%, 80.0%, and 77.8%, respectively. The sensitivity, specificity, PPV, and NPV of p16INK4a immunostaining plus HPV chip test for predicting tissue-HSIL+ were 71.2%, 86.4%, 84.2%, and 79.2%.
CONCLUSIONS
p16INK4a immunostaining as well as HPV chip testing with remaining LBCS with ASC-H are useful objective markers for the prediction of tissue-HSIL+.

Citations

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  • Usefulness of p16INK4a Immunocytochemical staining for the Differentiation between Atrophy and ASCUS in Diagnosis of Uterine Cervical Cancer
    Hye Ryoung Shin, Taekil Eom, Wan-Su Choi
    Biomedical Science Letters.2023; 29(3): 144.     CrossRef
Case Report
Fine Needle Aspiration Cytology of Inflammatory Myofibroblastic Tumor of Lung: A Case Report.
Gyeongsin Park, Kyungji Lee, Sun Mi Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang, Youn Soo Lee
Korean J Cytopathol. 2006;17(1):63-68.
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AbstractAbstract PDF
Inflammatory myofibroblastic tumor (IMT), normally referred to as inflammatory pseudotumor, is a fairly rare condition. Fine needle aspiration cytology (FNAC) of IMT has only rarely been reported. Here, we describe one such case of pulmonary inflammatory myofibroblastic tumor. A 30-year-old man presented with a 2.8cm-sized mass in his lung. Chest CT revealed a well defined, poorly enhancing mass. FNAC showed some fascicular or swirled clusters of spindle cells, admixed with occasional inflammatory cells and foamy histiocytes. The majority of the tumor cells evidenced bland, elongated nuclei, but infrequent pleomorphic nuclei. Some of the tumor cells evidenced nuclear grooves and intranuclear inclusions. Although the cytological differentiation of IMT from malignant lesions is not immensely problematic, due to the general paucity of cytological and nuclear atypia, a definite cytological diagnosis of IMT cannot be rendered simply by FNAC. Therefore, a diagnosis of IMT may be suggested via exclusive diagnosis.
Original Article
Evaluation for Cytopreservability of Manual Liquid-Based Cytology Liqui-PREP(TM) and its Application to Cerebrospinal Fluid Cytology: Comparative Study with Cytospin.
Gyeongsin Park, Kyungji Lee, Chan Kwon Jung, Dae Hyoung Lee, Bin Cho, Youn Soo Lee, Sang In Shim, Kyo Young Lee, Chang Suk Kang
Korean J Cytopathol. 2007;18(1):46-54.
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AbstractAbstract PDF
Cerebrospinal fluid (CSF) cytology is an effective tool for evaluating diseases involving the central nervous system, but his technique is usually limited by its low cellularity and poor cellular preservation. Here we compared the manual liquid-base Liqui-PREPTM (LP) to the cytospin (CS) with using a mononuclear cell suspension and we applied both methods to the CSFs of pediatric leukemia patients. The cytopresevability, in terms of cell yield and cell size, and the clinical efficacy were evaluated. When 2000 and 4000 mononuclear cells were applied, LP was superior to CS for the cell yield, 16.8% vs 1.7% (P=0.001) and 26.2% vs 3.5% (P=0.002), respectively. The mean size of the smeared cells was 10.60 micrometer in the CS, 5.01 micrometer in the LP and 6.50 micrometer in the direct smear (DS), and the size ratio was 1.7 (CS to DS), 0.8(LP to DS) and 2.1 (CS to LP), respectively. As compared to the cells in the DS, the cells in the CS were significantly enlarged, but those in the LP were slightly shrunken. Upon application to 109 CSF samples, 4 were diagnosed as positive for leukemia (positive), 4 had atypical cells and 101 were negative by CS; 6 were positive, one had atypical cells and 102 were negative by LP. For six cases, in which 4 were positive for leukemia and 2 of 4 had atypical cells by CS, they were positive by LP and they were also confirmed as positive according to the follow-up study. Three cases diagnosed as atypical cells (two by CS and one by LP), were confirmed as negative. In conclusion, these results suggest that LP is superior to CS for the cytopresevability and for rendering a definite diagnosis of cerebrospinal fluid.
Case Report
An Unusual Stroma-Rich Variant of Castleman's Disease of the Hyaline-Vascular Type: A Case Report.
Ji Han Jung, Gyeongsin Park, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2007;41(4):266-270.
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AbstractAbstract PDF
The stroma-rich variant of Castleman's disease of the hyaline-vascular type (CDHV) is a rare entity that shows overgrowth of a variety of stromal cells in the widened interfollicular (IF) area. We report here on a case of a stroma-rich variant of CDHV in an 18-year-old man who presented with an asymptomatic solitary neck mass he'd had for 1 year. Histologically, an enlarged lymph node fulfilled the criteria of CDHV, along with vague nodularity of a widened IF area. The nodular lesion consisted of numerous vessels and a proliferation of spindle cells. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin, they were negative for desmin, CD21, CD34, CD68, ALK-1, and S-100 protein. This stromal lesion is typically hyperplastic and clinically benign, and it must be distinguished from neoplastic stromal proliferation associated with Castleman's disease because of its potential for recurrence and metastasis.
Original Articles
Mucin Phenotype and CDX2 Expression as Prognostic Factors in Gastric Carcinomas.
Chan Kwon Jung, Kyo Young Song, Gyeongsin Park, Cho Hyun Park, Myeong Gyu Choi, Young Seon Hong, Kyo Young Lee
Korean J Pathol. 2007;41(3):139-148.
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AbstractAbstract PDF
Background
: Mucin phenotypic markers and CDX2 are widely expressed in gastric carcinomas, however, recent studies have produced conflicting results regarding whether the expression patterns of these markers have clinicopathologic significance.
Methods
: We examined samples from 217 gastric carcinoma patients immunohistochemically to determine if the expression of mucin phenotypic markers and CDX2 was correlated with postoperative survival and other clinicopathologic factors.
Results
: All tumors were phenotypically classified as gastric (type G, 81 cases), gastric and intestinal mixed (type GI, 55 cases), intestinal (type I, 43 cases), or unclassified (type U, 38 cases). The occurrence of type G and GI tumors was positively correlated with tumor progression whereas that of type U tumors was negatively correlated with tumor progression. CDX2 expression was correlated with type I tumors. Tumors that expressed MUC5AC or MUC6 had a better prognosis than those that did not. When the relationship between phenotype and prognosis was considered, type GI had the best prognosis, followed by type G, then type U.
Conclusions
: The mucin phenotypic markers may be useful for predicting tumor progression and survival in patients with gastric carcinomas. Additionally, CDX2 may play an important role in gastric carcinogenesis of type I tumors.
Expression of p73 in Non-small Cell Lung Carcinomas.
Ji Han Jung, Gyeongsin Park, Chan Kwon Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2007;41(2):109-115.
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AbstractAbstract PDF
BACKGROUND
The p73 is a recently identified homologue of the tumor suppressor gene, p53, and it has been found to induce apoptosis and inhibit cell proliferation. However, its role in the development of tumors is unclear. This study examined the expression of p73 in patients with non-small cell lung carcinomas (NSCLCs) to determine its clinical significance and association with the expressions of p53, pRb, and mdm2.
METHODS
A total of 183 NSCLCs were analyzed immunohistochemically using a tissue microarray.
RESULTS
The p73 protein was expressed in the cell nuclei in 156 (85.2%) out of the 183 cases. There was no correlation between the p73 expression and the clinicopathological variables. However, there was a correlation between the p73 expression and the mdm2 and pRb expressions. Multivariate Cox survival analysis identified tumor size and lymph node metastasis to be independent prognostic factors, but the p73 expression was not found to be associated with the patients' survival.
CONCLUSIONS
p73 is commonly expressed in NSCLC and it might, in conjunction with pRb and mdm2, be involved in the development of these tumors.
The Expression of Telomerase Reverse Transcriptase Protein is an Independent Prognostic Marker in Early Stage Non-Small Cell Lung Carcinomas.
Ji Han Jung, Chan Kwon Jung, Ahwon Lee, Gyeongsin Park, Jinyoung Yoo, Kyo Young Lee
Korean J Pathol. 2007;41(2):95-102.
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AbstractAbstract PDF
BACKGROUND
The catalytic subunit of telomerase, hTERT (telomerase reverse transcriptase), is one of the most important components of telomerase, and performs a pivotal role in the mechanism underlying the regulation of telomerase activity in cellular immortalization and carcinogenesis. The principal objective of this study was to investigate hTERT expression in patients with non-small cell lung carcinomas (NSCLCs), and to evaluate its clinical significance and association with the expression of p16 and p53.
METHODS
Using tissue microarray, the protein expression profiles of hTERT, p16 and p53 were investigated via immunohistochemistry in 167 samples of NSCLCs.
RESULTS
Expression was observed in 54.5% (91/167) of the tumors, which were predominantly squamous cell carcinomas. Patients evidencing hTERT expression in their tumors exhibited significantly poorer survival rates than did patients without hTERT expression in early-stage NSCLCs (p=0.0125). According to the results of our Cox regression analysis, hTERT expression proved to be an independent prognostic factor (p=0.006), particularly for squamous cell carcinomas (p=0.019). hTERT expression was not correlated with p16 expression, but was rather associated with the expression of p53 (p=0.002).
CONCLUSIONS
Our results show that hTERT may perform a function in the progression of NSCLC, and that its detection may be useful in predicting the prognosis of NSCLC patients in the early stages of the disease, as well as in the development of a targeted therapy in these tumors.
Expressions of Cyclin E-pathway Proteins (cyclinE, cdk2, p21, p27, p57) and Their Prognostic Significance in Non-small Cell Lung Carcinomas.
Ji Han Jung, Gyeongsin Park, Myung Ah Lee, Jae Ho Byun, Chan Kwon Jung, Heejeong Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang
Korean J Pathol. 2006;40(1):24-31.
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AbstractAbstract PDF
BACKGROUND
The aberrant expression of cyclins, cdk and cdk inhibitor has been shown to be involved in oncogenic transformation. The aim of this study was to investigate the expression of the cyclin E-pathway proteins (cyclin E, cdk2, p21, p27, p57) in human non-small cell lung carcinomas (NSCLC) and also to evaluate the clinical significance of these expressions.
METHODS
A total of 203 consecutive patients with completely resected pathological stage I-III NSCLC were retrospectively reviewed. The expressions of cyclin E, cdk2, p21, p27 and, p57 was examined by performing immunohistochemistry with using the tissue microarray method.
RESULTS
In the total cases, the expression levels of cyclin E, cdk2, p21, p27 and p57 were 39.9% (81/203), 48.3% (98/203), 68.0% (138/203), 32.5% (66/203) and 2.7% (5/203), respectively. The overexpression of cyclin E and cdk2 was significantly and inversely correlated with the histologic differentiation in the adenocarcinoma (p<0.05), but not in the squamous cell carcinoma. Among the clinicopathologic factors, the stage and lymph node metastasis were associated with overall survival (p<0.05). Among these proteins, the negative expression of p21 was significantly correlated with a shortened survival rate (p<0.05).
CONCLUSIONS
These data suggest that the overexpression of cyclin E and cdk2 and the loss of p21 and p27 are associated with tumor progression in NSCLC. The aberrant expression of p21 is correlated with a poor prognosis. Therefore the immunohistochemical analysis of this protein as well as the clinical stage and, lymph node metastasis may be useful tools for evaluating the prognosis of NSCLC patients.

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