Journal of Pathology and Translational Medicine

Original Articles

Increased Expression of Thymosin β4 Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer: Seung Yun Lee, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Chang Nam Kim, Joo Heon Kim, Dong Wook Kang; J Pathol Transl Med. 2017;51(1):9-16. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.08.23

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Background
Thymosin β₄ is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β₄ expression in human colorectal cancers (CRCs).
Methods
We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β₄ expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series.
Results
High expression of thymosin β₄ was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β₄ showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β₄ and HIF-1α were overexpressed and that thymosin β₄ expression increased in parallel with HIF-1α expression in CRC.
Conclusions
A high expression level of thymosin β₄ indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β₄ is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.

Citations

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Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis
Joanna I. Lachowicz, Giusi Pichiri, Marco Piludu, Sara Fais, Germano Orrù, Terenzio Congiu, Monica Piras, Gavino Faa, Daniela Fanni, Gabriele Dalla Torre, Xabier Lopez, Kousik Chandra, Kacper Szczepski, Lukasz Jaremko, Mitra Ghosh, Abdul-Hamid Emwas, Mass
International Journal of Molecular Sciences.2022; 23(1): 551. CrossRef
Metal coordination of thymosin β4: Chemistry and possible implications
Joanna Izabela Lachowicz, Mariusz Jaremko, Lukasz Jaremko, Giuseppina Pichiri, Pierpaolo Coni, Marco Piludu
Coordination Chemistry Reviews.2019; 396: 117. CrossRef
Adipose-Derived Mesenchymal Stem Cells Enhance Ovarian Cancer Growth and Metastasis by Increasing Thymosin Beta 4X-Linked Expression
Yijing Chu, Min You, Jingjing Zhang, Guoqiang Gao, Rendong Han, Wenqiang Luo, Tingting Liu, Jianxin Zuo, Fuling Wang
Stem Cells International.2019; 2019: 1. CrossRef
An Investigation on the Therapeutic Effect of Thymosinβ4 and Its Expression Levels in Streptozotocin-Induced Diabetic Mice
Kyung Sook Cho, Dong-Jin Kim, Bomee Shim, Jung Yeon Kim, Jun Mo Kang, Seon Hwa Park, Sang-Ho Lee, Hyung-In Yang, Kyoung Soo Kim
BioMed Research International.2018; 2018: 1. CrossRef
Hypoxia-inducible factor-1α expression in colorectal carcinoma
Ahmed M. Abd ElAziz, Hanan S. Abd ElHamid, Rasha R. Mostafa, Yousra R.A. Shalaby
Egyptian Journal of Pathology.2018; 38(1): 18. CrossRef

The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients.: Tae Hwa Baek, Joo Heon Kim, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Hyun Ki Soon, Chang Nam Kim, Che Myong Ko, Dong Wook Kang; Korean J Pathol. 2011;45(5):445-454.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.445

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Abstract PDF: BACKGROUND
Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs).
METHODS
Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated.
RESULTS
CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis.
CONCLUSIONS
Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.

Case Report

Langerhans Cell Sarcoma Arising in a Lymph Node: A Case Report and Review of the Literature.: Dong Wook Kang, Hyun Jin Son, Tae Hwa Baek, Hye Kyung Lee, Joo Ryung Huh, Joo Heon Kim, Mee Ja Park; Korean J Pathol. 2011;45(1):101-105.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.101

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Abstract PDF: We report a case of Langerhans cell sarcoma presented as a solitary mass in the left supraclavicular area in a 31-year-old woman. Computed tomography revealed a relatively well-defined and lightly enhancing mass in the left supraclavicular area, measuring 5.5x4.5x3.2 cm. Excision was subsequently performed. Microscopically, the specimen consisted of an enlarged and partially effaced lymph node. Nests of different size composed of atypical tumor cells were located in the paracortex and the medulla of the lymph node. The tumor cells exhibited abundant eosinophilic or clear cytoplasm and displayed marked nuclear atypia and increased mitotic figures. Infiltration of many eosinophils was identified in the periphery and between the tumor cells. The tumor cells were reactive for CD1a and S100 protein. Ultrastructually, they were found to have Birbeck granules in the cytoplasm.

Original Articles

Pathologic Characteristics of Ovarian Hemorrhagic Polycyst in Estrogen Receptor-alpha (ERalpha) Knockout Mice and Roles of ERalpha in Hemorrhagic Polycyst.: Hyun Jin Son, Joo Heon Kim, Hye Kyung Lee, Mee Ja Park, Dong Wook Kang, Che Myong Ko; Korean J Pathol. 2010;44(4):376-383.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.376

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Abstract PDF: BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERalphaKO) mice display several pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERalphaKO mice using a CreloxP approach and intra-ovarian ERalpha function as regulating key aspects of PCOS.
METHODS
ERalphaKO mice, which were deficient in exon 3 of the ERalpha gene, were used. Immunohistochemical studies were done on ovaries of control and ERalphaKO mice using antibodies specific to ERalpha, ERbeta, inhibin-alpha, and alpha-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B.
RESULTS
All ovaries of ERalphaKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERalphaKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of alpha-SMA.
CONCLUSIONS
ERalphaKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERalpha is the functional key to the pathogenesis of PCOS.

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 Reports

Primary Synovial Sarcoma of the Kidney: A Case Report and Literature Review.: Mee Ja Park, Tae Hwa Baek, Joo Heon Kim, Dong Wook Kang, Hye Kyung Lee, Hyun Jin Son; Korean J Pathol. 2009;43(3):274-278.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.274

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Abstract PDF

Synovial sarcoma is a rare renal neoplasm that is not easy to diagnose unless SYT-SSX fusion transcripts are identified. We report here on a case of primary renal synovial sarcoma in a 35-year-old woman. A mass was discovered by accident in the lower part of the right kidney when ultrasonography was performed, and it was removed via radical nephrectomy. Grossly, the tumor was a homogeneously tan-brown soft mass that measured 4.5x3.2x3.0 cm, and it was encircled by a well-defined cystic space. The lesion exhibited hypercellularity of the oval or short spindle cells that were arranged in various solid sheets or intersecting fascicles. Immunohistochemically, the tumor showed diffuse positivity for vimentin, bcl-2 and CD99, and it showed focal positivity for epithelial membrane antigen. The SYT-SSX fusion transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR). Synovial sarcoma should be considered in the differential diagnosis when a spindle cell neoplasm is encountered in the kidney.

Citations

Citations to this article as recorded by

Primary Renal Synovial Sarcoma and Clinical and Pathological Findings: a Systematic Review
Leandro Blas, Javier Roberti
Current Urology Reports.2021;[Epub] CrossRef
Primary Renal Synovial Sarcoma - A rare histology
Premkumar Krishnappa, Mohan keshavamurthy, Shakir Tabrez, Sreeharsha Harinatha, Mohan Balaiah Aswathaiya
Urology Case Reports.2020; 33: 101402. CrossRef

Cytologic Features of Ascitic Fluid Complicated by Small Cell Variant T-cell Prolymphocytic Leukemia: A Case Report.: Mee Ja Park, Insun Kim, Seung Yong Paik; Korean J Cytopathol. 2008;19(2):168-172.; DOI: https://doi.org/10.3338/kjc.2008.19.2.168

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Abstract PDF: T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell lymphoproliferative disorder with a post-thymic mature T-cell phenotype. The disease is characterized by rapidly rising lymphocytosis, lymphadenopathy, and splenomegaly. The clinical course is usually aggressive and progresses with frequent skin lesions and serous effusions. In 25% of cases, leukemic cells are small and tumor cells may not have a discrete nucleolus under light microscopy. Although the presence of characteristic cytoplasmic protrusions or blebs in tumor cells is a common morphologic finding in the peripheral blood film irrespective of the nuclear features, small cell variants lacking the typical nuclear features can cause diagnostic problems in clinical cytology. Furthermore, the small leukemic cells can share some cytologic findings with lymphocyte-rich serous effusions caused by non-neoplastic reactive lymphocytosis as well as other small lymphocytic lymphoproliferative disorders. Here, we describe the cytological findings of ascitic fluid complicated by small cell variant T-PLL in a 54-year-old man, the cytology of which was initially interpreted as small lymphocytic malignancy such as small lymphocytic lymphoma/chronic lymphocytic leukemia.

Original Articles

Correlation of the Intestinal Metaplasia Subtypes and Gastric Carcinoma.: Hwa Eun Oh, Mee Ja Park, Jong Sang Choi; Korean J Pathol. 1997;31(12):1272-1281.

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Abstract PDF: Helicobacter pylori, loss of basement membrane, atrophy, type III intestinal metaplasia, adenomatous polyposis coli (APC) gene mutations and altered p53 function were believed as a factor to develop the gastric adenocarcinomas. To investigate the incidence and prevalence of Helicobacter pylori, intestinal metaplasia and atrophy, 120 gastrectomy specimens collected from patients with gastric adenocarcinoma (100 cases) and non-neoplastic conditions (20 cases) were studied. Intestinal metaplasia can be classified as type I (complete), type II (incomplete, sulfomucin-negative) and type III (incomplete, sulfomucin-positive) by Filipe and Jass. The incidence of intestinal metaplasia of gastric adenocarcinoma was 96% compared with the incidence of 75% in non-neoplastic conditions. The type I and type II were more common than type III and were present in both non-neoplastic conditions (75%) and adenocarcinoma (74%). In contrast, type III intestinal metaplasia was seen in only 20% of intestinal metaplasia-positive cases, all of which (22 of 22) were from patients with adenocarcinoma. The high specificity of type III intestinal metaplasia might be acceptable for screening purposes, but its sensitivity of 22% for gastric adenocarcinoma is low. Helicobacter pylori were detected in 96% of adenocarcinoma cases and 100% of non-neoplastic cases. Atrophy was detected in 50% of non-neoplastic cases and in 57% of adenocarcinoma cases. The data thus confirms a significant relation between incomplete sulfomucin-secreting intestinal metaplasia (type III) and gastric carcinoma, especially intestinal type (p<0.01). Thus, the type III intestinal metaplasia should be considered a risk factor and its presence in a biopsy specimen should prompt close surveillance.

Expression Patterns of S100A6 Gene in Human Thyroid Diseases.: Joo Heon Kim, Jae Wha Kim, Seon Young Yoon, Jong Hyuck Joo, In Seong Choi, Mee Ja Park; Korean J Pathol. 2000;34(11):934-940.

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Abstract PDF: S100A6 (calcyclin) is a member of the S100 family and has been originally isolated from the cDNA library of Syrian baby hamster kidney cells. The S100A6 gene expression is reported to remain high throughout the cell cycle following induction by serum or growth factors, suggesting that the gene may be required for cell cycle progression. Nevertheless, the role that S100A6 may play in tumor progression remains unknown. In this study, we have explored the expression patterns of S100A6 gene in human thyroid tissues by northern blot analysis. Using the S100A6 monoclonal antibody, we carried out the immunohistochemical staining to determine the distribution/localization of S100A6 protein within tumor or non-tumorous cells of the thyroid. To modulate the regulation of endogenously expressed S100A6 protein in the intracellular level, overexpressed or anti-sense treated transfectant was constructed by using the eukaryotic expression vector. As a result, immunohistochemistry for S100A6 showed a strong positivity in the malignant tumors of thyroid and a high expression level of S100A6 protein affected cell proliferation in the overexpressed transfectant. These findings suggest that S100A6 may be involved in the tumor pathogenesis and provides another parameter for the differentiation of malignant and benign lesions. A well defined monoclonal antibody against S100A6 protein is now available for the immunohistochemical studies of the various thyroid tissues.

Fine Needle Aspiration Cytology of Mucoepidermoid Carcinoma of the Salivary Gland.: Jeong Seok Moon, Hwa Eun Oh, Joo Han Lee, Aee Ree Kim, Chul Hwan Kim, Han Kyeom Kim, Mee Ja Park, Nam Hee Won; Korean J Cytopathol. 1997;8(2):135-142.

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Abstract PDF: PURPOSE: There is no specific treatment guidelines for Henoch-Schonlein (HS) nephritis. Therefore we performed this study to observe the effect of long term steroid therapy combined with azathioprine METHODS: Treatment protocols; 1) Steroid pulse therapy: methylprednisolon 30 mg/kg/dose, maximum 1 gm, intravenously 6 times for alternate day. 2) Oral steroid was given 2 mg/kg/day for 1 month, 1 mg/kg/day for following I month and alternate day oral steroid combined with azathioprine 2 mg/kg/day for 2 years. RESULTS: Time period from HSP to onset of HS nephritis was between 2 weeks to 5 months with mean 7.4+/-7.4 weeks. Clinical remission were seen in 4 cases out of 5 (80%). Mean time period with disappearance of proteinuria and microscopic hematuria were 5+/-2.4 month and 13.3+/-2.9 month respectively. On pathologic findings by ISKDC, 3 cases were grade IIIb, 2 cases were grade IV in first kidney biopsies and showed pathologic improvement in follow up kidney biopsies after 2 years treatment. CONCLUSION: As there no definitive treatment for HS nephritis so far, our study of long term oral steroid therapy with azathioprine was effective in clinical and histologic aspect. Therefore further study in HS nephritis with in a large group will be needed in the future.

Fine Needle Aspiration Cytology of the Breast Lesions: Application of the Masood's Scoring System.: Ae Lee Kim, Hye Sun Kim, Han Kyeom Kim, Nam Hee Won, Mee Ja Park, Bum Hwan Koo; Korean J Cytopathol. 1998;9(1):45-54.

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Abstract PDF: Fine needle aspiration cytology is considered as a useful diagnostic procedure in management of patients with breast lesions. This study was undertaken to evaluate the scoring system of Masood in the interpretation of breast aspirates, to establish the most useful cytologic criteria for the diagnosis of breast lesions, and to subclassify the benign breast diseases. To assess the feasibility of a cytologic grading system, 57 cases of benign breast disease, 61 cases of malignant breast disease were studied, respectively. The aspirates were evaluated for the cellular arrangement, the degree of cellular pleomorphism and anisonucleosis, and the presence of myoepithelial cells and nuceoli. Values ranging from 1 to 4 were assigned to each criterion and the sum of the individual values was made for each case. The presence of stroma, apocrine metaplasia, foamy histiocytes and inflammatory cells, background of the smear, and cellularity were also evaluated. Cut-off value of the scoring system of Masood between benign and malignant lesion was 15. Among the cytologic criteria, cellular arrangement, presence of myoepithelial cells, nucleoli, and stroma, status of chromatin pattern, and background of smear were useful criteria in the differentiation between benign and malignant lesions. Application of the scoring system of Masood does not always make the accurate diagnosis and the subclassification of benign breast disease.

Polymerase Chain Reaction Detection of Mycobacterium tuberculosis and Fine Needle Aspiration Cytology for the Diagnosis of Tuberculous Lymphadenitis .: Joo Heon Kim, Nam Hoon Kim, Dong Wook Kang, Mee Ja Park, Sang Kyoung Moon, Tae Cho Yu, Eun Ju Jang; Korean J Cytopathol. 2001;12(1):25-30.

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Abstract PDF: Tuberculous lymphadenitis is not uncommon in Korea. Therefore, an inexpensive, safe and rapid method is needed to diagnose the tuberculous lymphadenitis. Fine needle aspiration cytology is a good method for this purpose, but has several limitations in the diagnosis of tuberculous lymphadenitis, especially when the presence of acid-fast bacilli is not proved. To evaluate the usefulness of the polymerase chain reaction with enzyme immunoassay technique in the detection of Mycobacterium tuberculosis (M. tuberculosis) in the cervical lymph node aspirates, the authors performed fine needle aspiration cytology and M. tuberculosis PCR with enzyme immunoassay for mycobacterial DNA sequences from 15 cases of the fine needle aspirates. Cytomorphologically, the cases were categorized into three types: predominantly necrotic materials; typical epithelioid cell granulomas with or without giant cells and caseous necrosis; and non-tuberculous lesions, such as reactive lymphadenitis, abscess, metastatic carcinoma and malignant lymphoma. M. tuberculosis DNA was found in 8 of 15 cases by PCR with enzyme immunoassay. Negative findings on PCR were achieved in 7 cases, which revealed non-tuberculous lymphadenopathy. In conclusion, we suggest that M. tuberculosis PCR with enzyme immunoassay using the fine needle aspirates is a very useful tool for the diagnosis of tuberculous lymphadenitis.

Case Report

Urinary Cytologic Findings of Small Cell Neuroendocrine Carcinoma: A Case Report.: Dong Hoon Kim, Dong Wook Kang, Kyung Hee Kim, Ju Heon Kim, Mee Ja Park; Korean J Cytopathol. 2002;13(2):78-83.

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Abstract PDF: We report the cytologic features of a case of primary small cell carcinoma of the urinary bladder with high grade transitional cell and signet ring cell carcinomatous components. A 64-year-old male presented with gross hematuria for one week. Computed tomography revealed an ill-defined mass in the left lateral wall of the urinary bladder. Urinary cytology showed hypercellularity with predominantly isolated single cells and clustered cells. They have scanty cytoplasm and naked hyperchromatic nuclei with finely granular nuclear chromatin and rare nucleoli. The tumor cells occurred predominantly singe cells, but a few in clusters. Nuclear molding was prominent. No glandular formation or nesting was noted. The second tumor cells had high nuclear/cytoplasmic ratio, irregular nuclear membrane, and coarse granular chromatin. The background was inflamed and necrotic. The histologic findings of transurethral resection were mainly composed of small cell carcinoma, and partly transitional cell and signet ring cell carcinomatous components. Small cell neuroendocrine carcinoma have distinctive cytologic features to make a proper diagnosis.

Original Article

Expression of Cyclin-Dependent Kinase-Associated Protein Phosphatase in Colorectal Carcinomas.: Chang Nam Kim, Soo Young Kim, Jae Wha Kim, Dong Wook Kang, Hyun Jin Son, Hye Kyung Lee, Mee Ja Park, Joo Heon Kim; Korean J Pathol. 2007;41(6):367-372.

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Abstract PDF: BACKGROUND
Cyclin-dependent kinase-associated phosphatase (KAP) is a human dual-specificity protein phosphatase that dephosphorylates Cdk2 on threonine160 in a cyclin-dependent manner and that is known as an up-regulated molecule in some malignant tumors. We investigated the expression and clinicopathologic significance of KAP protein in relation to tumorigenesis of colorectal carcinoma.
METHODS
The expression patterns of KAP protein in tumor tissue were examined by reverse transcription-PCR and immunohistochemical staining.
RESULTS
An enhanced transcriptional level of KAP mRNA was observed in 11 out of 12 colorectal carcinoma specimens. Immunohistochemical examination showed that KAP protein was more highly expressed in the tumors than that in the adjacent non-neoplastic mucosal tissues for 52 of 102 colorectal cancer tissues. The statistical analysis showed that an increased level of KAP protein in the colorectal cancer tissues was inversely correlated with the histologic grade, tumor size and Duke's stage.
CONCLUSION
The present study suggests that alteration of KAP might play a role, at least in part, in the tumorigenicity of colorectal carcinoma through the mechanism of cell cycle regulation.

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.

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