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

Citations to this article as recorded by

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

Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma: Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim; J Pathol Transl Med. 2016;50(5):355-360. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.05.19

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Abstract PDF: Background
There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings.
Methods
We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma.
Results
From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings.
Conclusions
Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.

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 Article

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.

Case Report

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

Original Article

Expression of p53 and Rb Proteins in Invasive Ductal Carcinoma of the Breast.: Hyun Jin Son, Han Sang Yoon, Myoung Jae Kang; Korean J Pathol. 1999;33(6):443-449.

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Abstract PDF: Inactivation of tumor suppressor genes may play an important role in many human cancers including breast. This study was done to determine the relationship between the expression of p53 and Rb protein and prognostic factors such as histopathologic differentiation, tumor size, and lymph node metastasis. In 57 cases of breast invasive ductal carcinomas, the immunohistochemical staining with p53 and Rb protein gave the following results: p53 protein was detected in 45.6% (26/57) of cases. Tumors with large size, poor differentiation or lymph node metastases tended to show increased expression of p53 protein. However, p53 protein expression did not show any significant correlation with prognostic factors such as tumor size (p value 0.25), histologic grade (p value 0.75), and positive lymph node status (p value 0.26). Rb protein was detected in 57.9% (33/57) of cases. Rb protein also did not show any significant correlation with prognostic factors such as tumor size (p value 0.56), histologic grade (p value 0.71), and positive lymph node status (p value 0.98). There was no significant correlation between p53 expression and Rb protein expression (p value 0.80).

Case Reports

Acinic Cell Carcinoma in the Nasal Cavity: A case report.: Hyun Jin Son, Myoung Ja Chung, Myoung Jae Kang; Korean J Pathol. 2000;34(1):88-92.

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Abstract PDF: The acinic cell carcinoma (ACC) is very rare in the nasal cavity. A 57-year-old woman suffered from nasal obstruction, postnasal dripping, and hyposmia for 2 months. Rhinoscopic examination revealed a huge polypoid mass in the right inferior and anterior nasal fossa of the nasal cavity and the mass was resected. The tumor showed the classic acinar and trabecular features of ACC on light microscopic examination. The finely granular cytoplasmic granules stained with periodic acid-schiff (PAS) and diastase digested-PAS, but not with alcian blue at pH 2.5 and mucicarmine. On ultrastructural examination, tumor cells contained numerous secretory granules diagnostic of ACC.

Heterotopic Prostatic Tissue with Cystic Change in Retrovesical Space: A case report.: Hyun Jin Son, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 2000;34(1):93-95.

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Abstract PDF: Heterotopic prostatic tissue has been reported in a variety of sites within and outside the urinary tract. Extra-urethral ectopic prostatic tissue is a distinct entity and may be more common than previously thought. We report a case of heterotopic prostatic tissue in 71-year-old man. Pelvic CT scan showed a well circumscribed cystic mass in the retrovesical space. Grossly, the tumor was 7.5 7.0 2.8 cm and revealed an ovoid unilocular cyst containing grayish amorphous granular materials. The prostatic origin of the tissue was confirmed by immunohistochemical staining for prostate specific antigen.

Multicystic Renal Dysplasia with Ipsilateral Ectopic Ureteral Orifice and Seminal Vesicle Cyst: A case report.: Hyun Jin Son, Joo Heon Kim, Myoung Jae Kang; Korean J Pathol. 2000;34(4):310-313.

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Abstract PDF: Renal dysplasia results from aberrant metanephric histogenesis caused fundamentally by a defect in inducer tissue or responding tissue. Dysplastic kidneys vary tremendously in gross and microscopic appearance but are characterized by abnormal organization and a mixed population of primitive structures, such as fetal or immature cartilage, dysplastic ducts, immature tubules, and undifferentiated mesenchyme. We report a case of unilateral multicystic renal dysplasia associated with an ipsilateral ectopic ureteral orifice entering a seminal vesicle cyst in a 33-year-old man. He was admitted due to primary infertility which had developed three years ago. The his semen analysis revealed oligospermia. No evidence of a family history of renal dysplasia was reported. Microscopic examination showed that the entire kidney was composed of cysts lined by flattened cells, dysplastic ducts and immature tubules surrounded by collars of spindle cells, primitive mesenchyme, and a few aberrantly formed glomeruli.

Inflammatory Myofibroblastic Tumor of the Maxillary Sinus: A case report.: Hyun Jin Son, Seung O Ko, Myoung Ja Chung, Ho Yeul Choi; Korean J Pathol. 2000;34(8):601-604.

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Abstract PDF: Inflammatory myofibroblastic tumor (IMT) is a space occupying lesion which is composed of myofibroblasts, plasma cells, and lymphocytes. IMT of the maxillary sinus is rare and its etiology is unknown. We present a case of inflammatory myofibroblastic tumor occurring in the right maxillary sinus of a 57-year-old woman. Radiologically, this tumor was interpreted as malignant neoplasm. On histologic examination, bundles of spindle cells were admixed with inflammatory cells including mature plasma cells and lymphocytes. On the basis of the immunohistochemical findings and ultrastructural features, we recognized that the intervening spindle cells were myofibroblasts. We discussed etiology and prognostic factors of this tumor.

Original Articles

Fine Needle Aspiration Cytology of Inflammatory Myofibroblastic Tumor in Mesentery: A Case Report.: Hyun Jin Son, Joo Heon Kim, Woo Sung Moon, Myoung Jae Kang, Ho Yeul Choi; Korean J Cytopathol. 2000;11(1):35-40.

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Abstract PDF: Since inflammatory myofibroblastic tumor was initially recognized in the lung, this tumor has been described in other extrapulmonary sites. In spite of relatively uniform histologic findings in various organs, a rarity in extrapulmonary sites and highly vascular characteristics frequently lead to a misdiagnosis in preoperative radiology and fine needle aspiration cytology. We present a case of inflammatory myofibro blastic tumor occurring in the mesentery of a 4-month-old girl. Fine needle aspira tion cytology smear disclosed characteristic spindle cells intermixed with prominent mature plasma cells and lymphocytes. According to the immunohistochemical staining, we recognized that the intervening spindle cells are myofibroblasts which have reactivity for the both actin and vimentin.

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

Benign Histiocytoma of the Lung: A Case Report.: Myoung Ja Chung, Min Ho Kim, Hyun Jin Son; Korean J Pathol. 2005;39(5):351-355.

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Abstract PDF: Histiocytomas have rarely been reported in the lungs. We report an unusual benign pulmonary histiocytoma in a 45-year-old man and discuss the differential diagnosis. Chest CT showed a well-defined solitary pulmonary nodule of approximately 3 cm in size in the posterobasal segment of the right lower lobe. Posterolateral thoracotomy and wedge resection was performed. Gross examination revealed a mass, measuring 2.2 x 2.1 cm that had a circumscribed margin within the lung parenchyma. Microscopically, the tumor was entirely composed of large polygonal to round cells with a few chronic inflammatory cells. These tumor cells contained abundant cytoplasm which was either granular, eosinophilic or foamy. Immunohistochemically, these cells were diffusely positive for CD68 and focally positive for 1-antitrypsin, but negative for cytokeratin, vimentin, and smooth muscle actin.

Original Article

Thrombospondin-1 and -2 Expressions in Hepatocellular Carcinomas: an Association with Tumor Angiogenesis and p53 Overexpression.: Jae Sin Chung, Ho Sung Park, Hyun Jin Son, Myoung Jae Kang, Woo Sung Moon; Korean J Pathol. 2005;39(4):215-221.

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Abstract PDF: Background
: It has been suggested that thrombospondin (TSP) is a p53-dependent negative regulator of tumor angiogenesis. TSP expression and localization in hepatocellular carcinomas (HCCs) and its association with overexpression of p53 protein were investigated. Methods : TSP-1 and -2 expressions were examined in 40 HCC specimens by immunohistochemical staining and in 4 HCC cell lines by Western blotting. In addition, p53 protein expression and microvessel density (MVD) were correlated with the TSP expression. Results : Strong immu- nopositivity for TSP-1 was observed in fibroblasts, vascular endothelial cells, and some vas- cular smooth muscle cells of the stroma in 18 cases (45%), and in tumor cells in 3 cases (7.5%) of 40 cases of HCC. Immunoreactivity for TSP-2 was observed in only the sinusoidal lining cells of the tumor in 15 cases (46%), and in tumor cells in 2 cases (6%) of 32 cases of HCC. TSP-1 expression was inversely correlated with MVD (p=0.028), but TSP-2 expression did not show any correlation with MVD. Although p53 was overexpressed in 17 cases, there was no significant correlation between TSP and p53 expressions. None of the HCC cell lines expressed TSP-1 or -2. Conclusions : These findings indicate that TSP-1 is mainly derived from nonparenchymal cells, and may decrease tumor angiogenesis in HCC.

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