Journal of Pathology and Translational Medicine

Original Articles

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors: Eun-Mi Son, Joo Young Kim, Soyeon An, Ki-Byung Song, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2015;49(1):30-36. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.23

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Background
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. Methods: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. Results: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. Conclusions: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

Citations

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Combined Infiltrative Macroscopic Growth Pattern and Infiltrative Microscopic Tumor Border Status Is a Novel Surrogate Marker of Poor Prognosis in Patients With Pancreatic Neuroendocrine Tumor
Bokyung Ahn, Joo Young Kim, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2023; 147(1): 100. CrossRef
Tumor-associated nonmyelinating Schwann cell–expressed PVT1 promotes pancreatic cancer kynurenine pathway and tumor immune exclusion
Chengcao Sun, Youqiong Ye, Zhi Tan, Yuan Liu, Yajuan Li, Wei Hu, Ke Liang, Sergey D. Egranov, Lisa Angela Huang, Zhao Zhang, Yaohua Zhang, Jun Yao, Tina K. Nguyen, Zilong Zhao, Andrew Wu, Jeffrey R. Marks, Abigail S. Caudle, Aysegul A. Sahin, Jianjun Gao,
Science Advances.2023;[Epub] CrossRef
Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors
Anne Menz, Rifka Bauer, Martina Kluth, Clara Marie von Bargen, Natalia Gorbokon, Florian Viehweger, Maximilian Lennartz, Cosima Völkl, Christoph Fraune, Ria Uhlig, Claudia Hube-Magg, Noémi De Wispelaere, Sarah Minner, Guido Sauter, Simon Kind, Ronald Simo
Human Pathology.2021; 115: 19. CrossRef
The molecular biology of pancreatic neuroendocrine neoplasms: Challenges and translational opportunities
Kate Young, Naureen Starling, Anguraj Sadanandam
Seminars in Cancer Biology.2020; 61: 132. CrossRef
Pancreatic acinar cell carcinomas and mixed acinar-neuroendocrine carcinomas are more clinically aggressive than grade 1 pancreatic neuroendocrine tumours
Joo Young Kim, Jacqueline A. Brosnan-Cashman, Jiyoon Kim, Soyeon An, Kyoung-Bun Lee, Haeryoung Kim, Do Youn Park, Kee-Taek Jang, Young-Ha Oh, Ralph H. Hruban, Christopher M. Heaphy, Seung-Mo Hong
Pathology.2020; 52(3): 336. CrossRef
Morphologic Variants of Pancreatic Neuroendocrine Tumors: Clinicopathologic Analysis and Prognostic Stratification
Yue Xue, Michelle D. Reid, Burcin Pehlivanoglu, Rebecca C. Obeng, Hongmei Jiang, Bahar Memis, Shu K. Lui, Juan Sarmiento, David Kooby, Shishir K. Maithel, Bassel El-Rayes, Olca Basturk, Volkan Adsay
Endocrine Pathology.2020; 31(3): 239. CrossRef
Histological grades and prognostic markers of well-differentiated pancreatic neuroendocrine tumor (WDPNET)
Yongchao Li, Daniel Rowan, Claire P. Williamson, Meiyun Fan, Ali G. Saad, Lizhi Zhang
Journal of Pancreatology.2020; 3(4): 188. CrossRef
Clinical and histopathologic prognostic implications of the expression of cytokeratins 8, 10, 13, 14, 16, 18 and 19 in oral and oropharyngeal squamous cell carcinoma
Rima A. Safadi, Niveen I. Abdullah, Rolla F. Alaaraj, Dima H. Bader, Darshan D. Divakar, Abed A. Hamasha, Maher A. Sughayer
Archives of Oral Biology.2019; 99: 1. CrossRef
Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies
Lingaku Lee, Tetsuhide Ito, Robert T Jensen
Expert Review of Anticancer Therapy.2019; 19(12): 1029. CrossRef
Carbonic anhydrase 9 expression in well-differentiated pancreatic neuroendocrine neoplasms might be associated with aggressive behavior and poor survival
Joo Young Kim, Sang Hwa Lee, Soyeon An, Sung Joo Kim, You-Na Sung, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Seung-Mo Hong
Virchows Archiv.2018; 472(5): 739. CrossRef
CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a potential predictor of progressive clinical courses
Yasuhiro Sakai, Seung-Mo Hong, Soyeon An, Joo Young Kim, Denis Corbeil, Jana Karbanová, Kyoko Otani, Kohei Fujikura, Ki-Byung Song, Song Cheol Kim, Masayuki Akita, Yoshihide Nanno, Hirochika Toyama, Takumi Fukumoto, Yonson Ku, Takanori Hirose, Tomoo Itoh,
Human Pathology.2017; 61: 148. CrossRef
Prognostic and predictive biomarkers in neuroendocrine tumours
David L. Chan, Stephen J. Clarke, Connie I. Diakos, Paul J. Roach, Dale L. Bailey, Simron Singh, Nick Pavlakis
Critical Reviews in Oncology/Hematology.2017; 113: 268. CrossRef
Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients
Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong
Journal of Pathology and Translational Medicine.2017; 51(4): 388. CrossRef
Prognostic significance of cytokeratin 19 expression in pancreatic neuroendocrine tumor: A meta-analysis
Dong Cen, Jiang Chen, Zheyong Li, Jie Zhao, Xiujun Cai, Aamir Ahmad
PLOS ONE.2017; 12(11): e0187588. CrossRef
A retrospective cohort study of pancreatic neuroendocrine tumors at single institution over 15 years: New proposal for low- and high-grade groups, validation of a nomogram for prognosis, and novel follow-up strategy for liver metastases
Liangtao Ye, Huilin Ye, Quanbo Zhou, Zhihua Li, Qing Lin, Langping Tan, Wenchao Gao, Zhiqiang Fu, Shangyou Zheng, Rufu Chen
International Journal of Surgery.2016; 29: 108. CrossRef
Correlating and Combining Genomic and Proteomic Assessment withIn VivoMolecular Functional Imaging: Will This Be the Future Roadmap for Personalized Cancer Management?
Bhakti Basu, Sandip Basu
Cancer Biotherapy and Radiopharmaceuticals.2016; 31(3): 75. CrossRef
Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts
Joo Young Kim, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2016; 140(5): 437. CrossRef

Oncocytoma and Oncocytic Carcinoma of the Salivary Glands, Single Institute Experience.: Jeong Hyeon Jo, Seung Ho Choi, Jong Lyel Roh, Soon Yuhl Nam, Sang Yoon Kim, Kyung Ja Cho; Korean J Pathol. 2010;44(4):370-375.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.370

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Abstract PDF

BACKGROUND
Oncocytic neoplasms of the salivary glands are rare and the differential diagnosis between oncocytic carcinomas (OCs) and oncocytomas is difficult. We present 5 cases of oncocytoma and 3 cases of OC of the salivary glands with clinicopathological and immunohistochemical comparisons.
METHODS
Eight cases of oncocytic neoplasms diagnosed at Asan Medical Center between 1998 and 2009 were reviewed for clinical data and histological features. Immunohistochemical staining for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her-2), c-kit, p53, and Ki-67 was done.
RESULTS
Cytological differences between oncocytomas and OCs were not obvious, but unequivocal infiltrative growths were identified in 3 cases, rendering the diagnosis of oncocytic carcinoma. When the remaining cases were classified as oncocytomas, there was no difference in age, size, and clinical symptoms between oncocytomas and OCs. Two of 3 OCs showed strong membranous expression of c-kit, but all oncocytomas were negative. The proportion of p53-positive cells was larger in OCs than oncocytomas. Her-2 or EGFR expression was absent, and Ki-67 labeling indices were less than 1% in all cases.
CONCLUSIONS
An infiltrative growth pattern, strong membranous expression of c-kit, and an increased proportion of p53-positive cells are features that can differentiate OCs from oncocytomas of the salivary glands.

Citations

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Primary oncocytic carcinoma of ectopic salivary gland: a unique case
E. Touli, A. Manganaris, C. Nikolaidou, I. Karasmanis
International Journal of Oral and Maxillofacial Surgery.2022; 51(4): 463. CrossRef

An Approach to Diagnosing Gastrointestinal Stromal Tumors Using Immunohistochemistry of c-kit and PDGFRA with Molecular Analysis.: Jeong Shik Kim, Jae Hoon Kim, Hyun Jin Oh, In Soo Suh, Jong Gwang Kim, Byung Wook Kang, Wan Sik Yu, Ho Young Chung, Han Ik Bae; Korean J Pathol. 2010;44(2):173-178.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.173

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Abstract PDF: BACKGROUND
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis.
METHODS
We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues.
RESULTS
Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11.
CONCLUSIONS
Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.

KIT/PDGFRA Expression and Mutation in Testicular Seminoma and Ovarian Dysgerminoma.: Song Yi Choi, Kwang Sun Suh, Yong Beom Kim, Hyun Jeong Lee, Eun Sun Kim, Mee Ja Park; Korean J Pathol. 2009;43(6):528-534.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.528

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Abstract PDF

BACKGROUND
KIT and PDGFRA are tyrosine kinase receptors. Stem cell factor/KIT-mediated signaling plays a role in normal spermatogenesis, and the alteration of KIT is important in the pathogenesis of seminomas/dysgerminomas (SD). METHODS: To determine the role of expression and mutation of the KIT and PDGFRA genes, we analyzed 16 seminoma cases, 4 spermatocytic seminoma (SS) cases and 8 dysgerminoma cases for KIT and PDGFRA expression and mutation of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR-SSCP methods. RESULTS: KIT was immunohistochemically positive in all 24 SD cases, and one of four (25%) SS cases. PDGFRA was immunohistochemically evident in 16 of the 24 (66.6%) SD cases, and two of the four (50%) SS cases. KIT expression was significantly reduced in SS compared with seminoma (p=0.0035). Four cases (14.3%) displayed mutation in KIT exon 17 or PDGFRA exon 12. Distant metastasis was present in three cases (10.7%), one of which had a nonsense mutation in KIT. CONCLUSIONS: These results indicate that KIT is expressed in the majority of SD cases, but not in most SS cases. However, there was no significant correlation between the clinicopathologic features and mutation or expression of KIT and PDGFRA.

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Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors
Sung Hee Jung, Kwang Sun Suh, Dae Young Kang, Dong Wook Kang, Young-Beum Kim, Eun-Sun Kim
Gut and Liver.2011; 5(2): 171. CrossRef

Case Report

Gastrointestinal Stromal Tumor of the Colon Mimicking Inflammatory Fibroid Polyp with a Novel 63 bp c-kit Deletion Mutation: A Case Report.: In Gu Do, Cheol Keun Park, Sung Hyun Yoon, John Goldblum, Kyoung Mee Kim; Korean J Pathol. 2009;43(4):374-377.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.374

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Abstract PDF: Colonic gastrointestinal stromal tumors (GISTs) are rare and behave aggressively compared to GISTs in other parts of the gastrointestinal tract. Therefore, accurate diagnosis of GISTs and their distinction from other mesenchymal tumors is important for proper patient management and follow-up. Herein, we present an unusual case of a colonic GIST mimicking an inflammatory fibroid polyp with a novel 63 bp deletion mutation in exon 11 of the c-kit gene, which has not previously been reported. The tumor consisted of loosely arranged spindle cells and many inflammatory cells scattered throughout the tumor. Immunohistochemically, the tumor cells were focally and weakly positive for c-kit and diffusely positive for CD34, but were negative for PKC-theta, SMA, S-100 protein, ALK-1, and desmin. Our case re-emphasizes the broad morphologic spectrum of GISTs.

Original Article

Immunohistochemical Study of IL-4, IL-6, and TNF Expression in Cardiac Myxoma: Emphasis on Constitutional Symptoms of the Myxoma Patients.: Min Sun Cho, Soo Yeon Cho, Mi Jung Kim, Sung Sook Kim, Jeong Wook Seo, Woon Sup Han; Korean J Pathol. 1995;29(5):563-571.

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Abstract: It is well documented that cardiac myxomas are associated with immunologic features that can simulate systemic autoimmune diseases. Recently, it was reported that cardiac myxomas produce IL-6 constitutively, which could partly explain the immunologic features observed in these patients. However, only a few investigators have studied cytokines in regards to symptoms they may cause in patients with cardiac myxoma. Also there is very little information in the literature on the immunohistochmical localization of IL-6. We performed immunobistochemical stains for IL-4, TNF, and IL-6 on paraffm embbeded tissue of cardiac myxoma tissue. A bioassay of IL-6 activity in patient's serum and in cultured cells from fresh myxoma tissue was performed to ascertain the role of these cytokines in myxomas. In this study, we demonstrated inununohistochemically that there was a local overproduction of IL-4, TNF, and IL-6 in cytoplasm of the tumor cells in about half cases. Bioassays of the serum and cultured tumor cells revealed elevated IL-6 activities. Also these findings correlate to production of patient's constitutional symptoms with statistical significance (P<0.05). In conclusion, these results are of considerable importance in understanding the role of IL-4, TNF, and IL-6 in cardiac myxoma patient with constitutional symptoms, and have an impact on strategies for diagnosis and therapy of cardiac myxoma.

Case Report

Malignant Gastrointestinal Stromal Tumor of the Esophagus: A Case Report.: Hae Joung Sul, Kyeong Hee Kim, Dae Young Kang; Korean J Pathol. 2001;35(3):252-255.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) predominate in the stomach and small intestine but have rarely been documented in the esophagus. We report a rare case of GIST of the esophagus in a 47-year-old woman. Histologically, the tumors showed a combination of solid, myxoid, and perivascular collar-like patterns, with spindle and epithelioid cells. The tumor cells were positive for CD117, CD34, and S-100 protein and negative for desmin and -smooth muscle actin.

Original Articles

Primary Extragastrointestinal Stromal Tumor (EGIST) of the Greater Omentum.: Kyung Un Choi, Jee Yeun Kim, Do Youn Park, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Jun Woo Lee; Korean J Pathol. 2001;35(4):347-350.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g. The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields. Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.

Immunohistochemical Expression of CD117, CD34, Vimentin and alpha-Smooth Muscle Actin in Gastrointestinal Stromal Tumors.: Jong Kuk Kim, O Jun Kwon, Byung Heon Kim; Korean J Pathol. 2001;35(6):506-512.

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Abstract: BACKGROUND
The interstitial cell of Cajal (ICC), the cell of origin for gastrointestinal stromal tumor (GIST), expresses CD117 (c-kit) which is a receptor for KIT ligand in cell membranes. It is immunohistochemically positive for CD117, CD34 and vimentin, but not for alpha-smooth muscle actin (SMA).
METHODS
We performed the immunohistochmical study with anti-CD117, anti-CD34, anti-VMT and anti-alpha-SMA in paraffin-embedded tissue of 28 GISTs and 19 smooth muscle tumors arising in the gastrointestinal tract, mesentery, omentum and retroperitoneum (GISMT) to determine the precise nature of GIST cells.
RESULTS
The positive rates of CD117, CD34 and vimentin in extraGISTs were significantly higher than in GISMTs. The positive rate of alpha-SMA in GIST was not significantly different than in GISMTs.
CONCLUSIONS
A subset of GISTs may express alpha-SMA as well as CD117 and the cell of their origin may be a ICC precursor cell which is capable of differentiating bidirectionally into ICC and smooth muscle cell. This explains why GISTs may arise out of gut where ICC is not present and that they may represent the tumors arising from ICC precursor cell present around the gastrointestinal tract.

Application of Epstein-Barr Virus Cell Lines (CCL85 EB-3) in Performing the EBER mRNA In Situ Hybridization as a Positive Control.: Sung Sook Kim, Woon Sup Han, Joo Young Suh, Joo Ryung Huh; Korean J Cytopathol. 1996;7(1):38-43.

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Abstract PDF: Epstein-Barr virus(EBV) is associated with a wide spectrum of benign and malignant disorders including leukoplakia, Hodgkin's lymphoma, central nervous system lymphoma, peripheral T cell lymphoma and nasopharyngeal undifferentiated carcinoma. There are several distinctive aspects of biology of the virus that are important in investigation of virus in clinical specimens. The abundant expression of the EBER mRNA transcripts makes possible the sensitive detection of latent expression in EBV-associated tumors. Although there has been a dramatic increased interest in the direct characterization of EBV in clinical specimens, there have been few studies about the effective and reliable positive controls in performing in situ hybridization technique for EBV, especially on paraffin-embedded tissue. We applied Burkitts lymphoma cell line as positive control in EBV in hydridization using Oncor Kit. The cell block of Burkitt lymphoma cell line(CCL85 EB-3) showed strong and specific positivity for EBER in situ in nuclei of EBV infected cells.

Case Report

Fine Needle Aspiration Cytological Findings of Burkitt lymphoma: A Brief Case Report.: Hyang Jeong Jo, Jung Taek Oh, Gang Deuk Kim, Hun Soo Kim; Korean J Cytopathol. 2007;18(2):175-177.

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Abstract PDF: A case of Burkitt lymphoma diagnosed through fine needle aspiration cytology is described. A 66-year-old man presented with lymphadenopathy on the right cervical neck and axillary area. An ultrasonogram and CT scan for the cervical neck showed a multiple variable sized lymphadenopathy with pericapsular invasion and necrotic foci. Fine needle aspiration cytology (FNAC) of the cervical lymph nodes revealed very cellular and necrotic smears consisting of diffusely scattered intermediate monotonous round cells, tingible body macrophages and many mitotic figures. Histological features of the excised lymph nodes showed the classic morphological features of Burkitt lymphoma. Recognition of the characteristic cytological features can suggest the possibility of Burkitt lymphoma.

Original Articles

Significance of c-kit and COX-2 Expression in Breast Tissue.: Eun Kyung Kim, Won Mi Lee, Jong Eun Joo, Sook Kyung Ko; Korean J Pathol. 2008;42(3):157-161.

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Abstract PDF: BACKGROUND
The proto-oncogene c-kit encodes a transmembrane tyrosine kinase growth factor receptor. Studies have shown that c-kit is highly expressed in normal breast epithelium, but expression is decreased in primary breast cancer. Cyclooxygenase-2 (COX-2) is an inducible enzyme that converts arachidonic acid to prostaglandins. Expression of COX-2 has been reported in malignant tumors including breast cancer. We evaluated the expression of c-kit and COX-2 in benign and malignant lesions of the breast to assess the roles of these proteins in cancer initiation and progression.
METHODS
We characterized 20 benign lesions, 20 intraductal carcinomas and 70 invasive breast carcinomas. Immunohistochemical staining for c-kit and COX-2 was performed.
RESULTS
Expression of c-kit was detected in 75% of the benign breast lesions, 40% of the intraductal carcinomas and 10% of the invasive carcinomas. COX-2 expression was observed in 80% of the benign lesions, 70% of the intraductal carcinomas and 52% of the invasive carcinomas. Expression of c-kit was significantly correlated with tumor size (p=0.02). COX-2 expression was significantly correlated with negative expression of estrogen receptor and progesterone receptor (p=0.02, p=0.04), Her-2/neu expression (p=0.008) and the high proliferation index (p=0.0002).
CONCLUSIONS
Our results suggest that c-kit and COX-2 might be involved in malignant transformation of the mammary epithelium and tumor progression. It is suggested that c-kit and COX-2 can be used as predictive markers and therapeutic targets.

Expression of c-kit and Cell Cycle Regulators in Non-small Cell Lung Carcinoma.: Sun Hee Chang, Mee Joo, Hanseong Kim; Korean J Pathol. 2006;40(6):427-431.

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Abstract PDF: BACKGROUND
The abnormal expression of c-kit is implicated in the pathogenesis of a variety of solid tumors. The Rb pathway and p53 act as cell cycle regulators. The purpose of this study was to assess the expression of c-kit, Rb, p53, p16 and cyclin D1 and their relationship to clinical and pathological parameters in patients with non-small cell lung carcinomas (NSCLC(s)).
METHODS
Tissue microarrays consisting of 2 mm cores from the corresponding blocks were constructed from 54 NSCLC(s). Immunohistochemical staining for c-kit, Rb, p53, p16 and cyclin D1 was performed. C-kit immunostaining was considered positive if > or =10% of tumor cells were immunoreactive along the membrane and/or in cytoplasm. For Rb, p53, p16 and cyclin D1, tumor cells showing a nuclear staining pattern were interpreted as positive.
RESULTS
We found that c-kit was expressed in 13 (24%) cases, Rb was lost in 39 (72%) cases, p53 was expressed in 28 (52%) cases, p16 was lost in 42 (78%) cases and cyclin D1 was expressed in 33 (61%) cases. The c-kit expression was significantly higher in adenocarcinoma (39%) than in squamous cell carcinoma (8%). We did not find any correlation between c-kit, Rb, p53, p16 and cyclin D1 expression and clinicopathological parameters such as: age, tumor size, lymph node involvement, disease stage and distant metastasis. There was a direct correlation between p53 expression and Rb loss.
CONCLUSIONS
These results suggest that c-kit may be a useful therapeutic target for patients with c-kit positive tumors, and that the disruption of Rb and p53 pathways may play an important role in the development and progression of NSCLC(s).

Case Report

Gastrointestinal Stromal Tumors associated with Neurofibromatosis Type I: A Report of Two Cases.: Joo Heon Kim, Ock Seong In, Seong Kyu Lee, Haing Woon Baik, Seong Ho Kim, Dong Wook Kang, Kyung Hee Kim, Mee Ja Park, Yong Il Kim; Korean J Pathol. 2006;40(2):137-141.

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Abstract PDF: Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract, but this tumor is rarely seen in association with type 1 neurofibromatosis (NF-1). We report here on two cases of multiple GISTs of the small intestine that occurred in NF-1 patients. We also analyzed the mutations of c-kit exons 9, 11, 13 and 17 and the plateletderived growth factor receptor-alpha (PDGFRA) exons 12 and 18 in two GIST patients. Histologically, the NF-1-associated GISTs were similar to those of non-the NF-1 GISTs, but they characteristically revealed hyperplastic interstitial cells of Cajal around the GISTs. Immunohistochemically, these tumors showed strong co-expressions of CD117 and CD34. The molecular genetic analysis of the GISTs showed that all of the c-kit and PDGFRA exons that were analyzed in the GISTs of the two patients were the wild-type, suggesting a limited role for the c-kit and PDGFRA mutations in the tumorigenesis of NF-1-associated GISTs.

Original Article

Tissue Microarray Analysis of the Expression of p53, c-kit and CD34 in Sarcomas.: Jinyoung Yoo, Kyung Shin Park, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2004;38(4):221-227.

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Abstract PDF: BACKGROUND
Our objectives in this study were to (1) evaluate the possible role of p53, c-kit and CD34 proteins in sarcomas and to determine their potential relationship; (2) use a tissue microarray to compare the immunohistochemical staining results on both the tissue microarrays and the corresponding whole tissue sections.
METHODS
Whole sections from 85 sarcomas were studied for the immunohistochemical expression of p53, c-kit and CD34. Tissue microarrays consisting of triplicate 2 mm cores from the corresponding blocks were constructed and stained according to the same protocols as those used for the whole sections.
RESULTS
On whole section analysis, p53 protein was expressed in 25 cases (29.4%). Expression of c-kit was observed in 31 specimens (36.5%), whereas CD34 expression was noted in 11 tumors (12.9%). The overall concordance between triplicates was 96% (217/226). The consensus score from the combined triplicates agreed with the results on the whole sections at 91.4% (233/255). The correlations between p53 and CD34, and between c-kit and CD34, were statistically significant (p=.028 and p=.010 respectively).
CONCLUSIONS
p53 and c-kit express relatively frequently in sarcomas. Tissue microarrays are an effective alternative to whole sections; however, the presence of triplicate punches seems to improve the yield but not the concordance of data.

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