Journal of Pathology and Translational Medicine

Original Articles

Evaluation of Protein Expression in Housekeeping Genes across Multiple Tissues in Rats: Hye Jeong Kim, Jong In Na, Byung Woo Min, Joo Young Na, Kyung Hwa Lee, Jae Hyuk Lee, Young Jik Lee, Hyung Seok Kim, Jong Tae Park; Korean J Pathol. 2014;48(3):193-200. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.193

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Background

Housekeeping genes, which show constant protein expression patterns between different tissue types, are very important in molecular biological studies as an internal control for protein research.

Methods

The protein expression profiles of seven housekeeping genes (HPRT1, PPIA, GYS1, TBP, YWHAZ, GAPDH and ACTB) in various rat tissues (cerebrum, cerebellum, cardiac ventricle and atrium, psoas muscle, femoral muscle, liver, spleen, kidney, and aorta) were analyzed by Western blot and compared by coefficient of variation (CV).

Results

HPRT1 was stably expressed (CV≤10%) in six tissues (cerebrum, cerebellum, ventricle, femoral muscle, spleen, and kidney), PPIA was stably expressed in five tissues (cerebrum, cerebellum, ventricle, spleen and kidney), YWHAZ was stably expressed in three tissues (cerebrum, cerebellum, and kidney), and GAPDH was stably expressed in four tissues (cerebrum, ventricle, psoas muscle, and kidney). In comparison, GYS1, TBP, and ACTB were found to have CV values over 10% in all tissues. Of the seven genes examined, four (HPRT1, PPIA, YWHAZ, and GAPDH) were found to be stably expressed across multiple organs, with low CV values (≤10%).

Conclusions

These results will provide fundamental information regarding internal controls for protein expression studies and can be used for analysis of postmortem protein degradation patterns in forensic medicine.

Citations

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Stefan Pittner, Valentina Bugelli, M. Eric Benbow, Bianca Ehrenfellner, Angela Zissler, Carlo P. Campobasso, Roelof-Jan Oostra, Maurice C. G. Aalders, Richard Zehner, Lena Lutz, Fabio C. Monticelli, Christian Staufer, Katharina Helm, Vilma Pinchi, Joseph
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Gabriel E. Vázquez-Vélez, Kristyn A. Gonzales, Jean-Pierre Revelli, Carolyn J. Adamski, Fatemeh Alavi Naini, Aleksandar Bajić, Evelyn Craigen, Ronald Richman, Sabrina M. Heman-Ackah, Matthew J.A. Wood, Maxime W.C. Rousseaux, Huda Y. Zoghbi
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Combined proteomic and miRNome analyses of mouse testis exposed to an endocrine disruptors chemicals mixture reveals altered toxicological pathways involved in male infertility
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Postmortem proteomics to discover biomarkers for forensic PMI estimation
Kyoung-Min Choi, Angela Zissler, Eunjung Kim, Bianca Ehrenfellner, Eunji Cho, Se-in Lee, Peter Steinbacher, Ki Na Yun, Jong Hwan Shin, Jin Young Kim, Walter Stoiber, Heesun Chung, Fabio Carlo Monticelli, Jae-Young Kim, Stefan Pittner
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Aging‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle
Dominika Drulis‐Fajdasz, Agnieszka Gizak, Tomasz Wójtowicz, Jacek R. Wiśniewski, Dariusz Rakus
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New insights into the distribution, protein abundance and subcellular localisation of the endogenous peroxisomal biogenesis proteins PEX3 and PEX19 in different organs and cell types of the adult mouse
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Identification of valid endogenous control genes for determining gene expression in C6 glioma cell line treated with conditioned medium from adipose-derived stem cell
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Sclerosing Mucoepidermoid Carcinoma in the Parotid Gland: Literature Review
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Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma.: Kyung Hwa Lee, Soong Lee, Hyeon Min Lee, Seung Chul Back, Sung Bum Cho, Jae Hyuk Lee; Korean J Pathol. 2011;45(4):397-405.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.397

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Abstract PDF

BACKGROUND
The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance.
METHODS
Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method.
RESULTS
Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041).
CONCLUSIONS
Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

Citations

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A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer
Pierina Cetraro, Julio Plaza-Diaz, Alex MacKenzie, Francisco Abadía-Molina
Cancers.2022; 14(7): 1671. CrossRef

Differences in Expression of VEGF-A, VEGFR-1, VEGFR-2 and Microvessel Density in Colorectal Cancer with Liver Metastasis.: Eun Hui Jeong, Young Kim, Byeong Woo Min, Kyung Hwa Lee, Hyun Soo Kim, Jae Hyuk Lee; Korean J Pathol. 2010;44(6):571-580.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.571

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Abstract PDF: BACKGROUND
Colorectal cancer (CRC) is one of the most common malignant neoplasms and is a leading cause of mortality worldwide. Metastasis to the liver is a frequent event in patients with CRC. An essential step in the metastatic cascade is angiogenesis.
METHODS
This study included 45 patients who underwent a partial colectomy with hepatic resection for CRC with hepatic metastases. Immunohistochemistry was performed using vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1, VEGFR-2, and CD34 antibodies to examine the relationship between CRC with liver metastases and angiogenesis.
RESULTS
CRC showed significantly stronger expression of VEGF-A, VEGFR-1, and VEGFR-2 than liver metastases (p < 0.05). Microvessel density was also higher in CRC than in liver metastases (p < 0.05).
CONCLUSIONS
Compared with previous studies, we found a higher expression of VEGF-A, VEGFR-1, VEGFR-2, and microvessel density in CRC than in liver metastases, which could be ascribed to a difference in vessel distribution and blood supply in each organ. Given its profuse blood supply and distinct cell populations, the liver might provide a rich milieu for tumor cell growth with less expression of angiogenesis-inducing agents.

Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.: Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee; Korean J Pathol. 2010;44(3):252-258.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252

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Abstract PDF

BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.

Citations

Citations to this article as recorded by

Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef
The Relationship Between Estrogen/Progesterone Receptor and Expression of mTOR/pAkt Proteins and the Analysis of Prognosis in Breast Cancer
Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
Journal of Breast Disease.2013; 1(1): 8. CrossRef
Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef

Aberrant Promoter Methylation of the Vimentin Gene in Colorectal Cancer Associated with the Adenoma-Carcinoma Sequence.: Mi Hee Cho, Yu Mi Lee, Jin Sook Kim, Hyun Soo Kim, Kyung Hwa Lee, Sang Woo Juhng, Jae Hyuk Lee; Korean J Pathol. 2010;44(2):179-186.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.179

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Abstract PDF

BACKGROUND
DNA hypermethylation is a common epigenetic finding in human cancers and is closely associated with transcriptional silencing. In the present study, we investigated the proportion of colorectal neoplasms that showed the adenoma-carcinoma progression and vimentin gene methylation.
METHODS
Methylation status of the vimentin gene was examined in nontumoral mucosa, adenomas, and adenocarcinomas from 45 colorectal cancer patients who had adenoma and adenocarcinoma together. Methylation status was determined by bisulfite modification and the methylation-specific polymerase chain reaction. The expression of the vimentin gene product was also examined by immunohistochemistry.
RESULTS
Promoter methylation of vimentin was detected in 80% (36 out of 45 cases) of adenocarcinomas, 82.2% (37 of 45) of adenomas, and 28.9% (13 of 45) of normal epithelia, and the difference between neoplastic and normal specimens was statistically significant (p < 0.001). However, no significant correlations were observed between methylation frequency and clinicopathologic variables. Immunohistochemically, vimentin expression was not observed in either normal epithelial cells or tumor cells. Protein expression and vimentin promoter methylation were not associated.
CONCLUSIONS
The frequency of aberrant methylation of the vimentin gene was high in colonic adenomas and adenocarcinomas. This result suggests that the methylation status of vimentin may be clinically beneficial in screening for colorectal cancer patients and may be helpful in clarifying colorectal cancer biology.

Citations

Citations to this article as recorded by

Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum
Margaret Thomas, Paola Marcato
Cancers.2018; 10(4): 101. CrossRef
Aberrant promoter methylation of beta‐1,4 galactosyltransferase 1 as potential cancer‐specific biomarker of colorectal tumors
Maria Luana Poeta, Emanuela Massi, Paola Parrella, Pasquale Pellegrini, Mariangela De Robertis, Massimiliano Copetti, Carla Rabitti, Giuseppe Perrone, Andrea Onetti Muda, Francesca Molinari, Elena Zanellato, Stefano Crippa, Damiano Caputo, Marco Caricato,
Genes, Chromosomes and Cancer.2012; 51(12): 1133. CrossRef

Case Report

Fine Needle Aspiration Cytology of Primay Malignant Lymphoma of the Breast: A Case Report.: Hyun Joong Kim, Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Ji Shin Lee, Chan Choi; Korean J Cytopathol. 2004;15(2):112-115.

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Abstract PDF: Lymphoproliferative disorders, manifesting either as a primary lesion or as part of a generalized process, rarely involve the breast. The primary malignant lymphoma of the breast is rare. The cytologic features of this neoplasm have not been reported in Korea thus far. We described a case of primary malignant lymphoma of the breast, as diagnosed by fine needle aspiration cytology (FNAC) in an 84-year-old female. FNAC smears showed high cellularity. The main cytologic feature observed was a carpeting of monotonous, atypical, enlarged lymphoid cells. These lymphocytes showed relatively round elliptical nuclei with some indentation. One or more prominent nucleoli were seen. Biopy from the breast mass revealed diagnostic features of non-Hodgkin's lymphoma, diffuse large B-cell type.

Original Article

Expression of VEGF, MMP-9 and Neovascularization in Relationship to the Clinical Behavior of Giant Cell Tumors of Bone.: Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Chang Woo Han, Sung Sun Kim, Sang Woo Juhng, Sung Taek Jung, Jae Hyuk Lee; Korean J Pathol. 2006;40(6):420-426.

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Abstract PDF: BACKGROUND
Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior.
METHODS
We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9.
RESULTS
The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022).
CONCLUSIONS
These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.

Case Reports

Thyroid Papillary Carcinoma with Exuberant Nodular Fasciitis-like Stroma: A Case Report.: Kyung Hwa Lee, Jae Hun Chung, Jung Han Yoon, Kyung Whan Min, Chan Choi, Ji Shin Lee; Korean J Pathol. 2006;40(1):76-79.

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Abstract PDF: Thyroid papillary carcinoma (TPC) with exuberant nodular fasciitis-like stroma is one of the rare variants of TPC. To date, only 19 cases have been reported in the English medical literature. We report here on the the first Korean case of TPC that contained a prominent nodular fasciitis-like stroma. A 40-year-old female presented with a hard painless right neck mass that had been present for two months. Total thyroidectomy disclosed a solitary nodule in the mid portion of the right lobe that measured 25 x 20 mm. The tumor was well delineated, but it was not encapsulated. Microscopically, the tumor was a typical papillary carcinoma except that large areas of the tumor were occupied by a stroma composed of irregular fascicular spindle cells. The stromal component accounted for 60% of the tumor mass. The spindle cells exhibited neither atypism nor mitosis, and the tumor's extensive stromal cell proliferation resembled the appearance of nodular fasciitis of the soft tissues. Immunohistochemically, the spindle cells were positive for vimentin and alpha-smooth muscle actin, but they were negative for thyroglobulin, thyroid transcription factor-1, S-100 protein, CD34 and desmin, and this represents myofibroblastic features.

Fibromatosis of the Breast: A Case Report.: Hyun Joong Kim, Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Ji Shin Lee, Chan Choi; Korean J Pathol. 2005;39(2):137-139.

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Abstract PDF: Fibromatosis of the breast is a rare tumor. We describe here a case of mammary fibromatosis in a 37-year-old woman. The mass from the right breast was 3 cm at the greatest dimension. The lesion was poorly circumscribed, firm and white-gray on the cut surface. Histologically, the lesion infiltrated into the lobules of the breast, and the tumor was composed of relatively uniform fibroblasts and collagen. Neither mitotic activity nor cellular atypia was seen. On the immunohistochemistry, the cells were positive for vimentin and they were focally positive for smooth muscle actin. Staining results for estrogen receptor and progesterone receptor were negative.

Original Articles

Clonal Analysis of Neurofibroma by PCR Amplification of HUMARA Gene.: Jae Hyuk Lee, Seung Sang Han, Hyun Sik Oh, Yoo Duk Choi, Hyun Joong Kim, Kyung Hwa Lee, Jong Hee Nam, Chan Choi, Sang Woo Juhng; Korean J Pathol. 2003;37(6):421-428.

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Abstract PDF: BACKGROUND
While neurofibromas have generally been regarded as polyclonal hyperplastic lesions, it remains unclear whether the tumor is a true neoplasm or a hyperplastic lesion.
METHODS
Determination of clonality by X chromosome inactivation pattern was investigated in twenty-one cases of neurofibroma employing enzyme digestion and PCR of the HUMARA gene. The histological, immunohistochemical, and ultrastructural characteristics of the tumors were also examined.
RESULTS
Immunohistochemically, most of the tumor cells showed vimentin and S-100 protein positivity. Axons were demonstrated by neurofilament protein positivity and were seen mainly at the periphery and rarely in the central portion of the tumor. Ultrastructurally, the tumors were composed of a variety of cell types: perineurial cells, Schwann cells, fibroblasts, and axons. X chromosome inactivation analysis was completed on thirteen out of fifteen cases in which DNA was successfully extracted. Of thirteen neurofibromas that were heterozygous at the HUMARA loci, eleven showed a polyclonal pattern. The remaining two cases were considered as indeterminate for clonality because of unequal band intensity and failure to obtain the normal control DNA.
CONCLUSION
The results from this study suggest that neurofibromas are polyclonal in origin and might be a neoplastic lesion comprising non-neoplastic cells among constituent components.

Neurofilament Protein Subtype Expression in Neuronal Migration Disorders.: Hyun Sik Oh, Yoo Duk Choi, Hyun Joong Kim, Kyung Hwa Lee, Myoung Kyu Kim, Young Jong Woo, Jae Hyu Kim, Min Cheol Lee; Korean J Pathol. 2003;37(6):413-420.

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Abstract PDF: BACKGROUND
Neuronal migration disorder (NMD) is one of the causes of medically intractable epilepsy. As neurosurgical treatments for medically intractable epilepsy have expanded recently, precise histopathologic diagnosis is required. Histopathologic grading of NMD is important due to its association with neocortical development and expectation of prognosis. Many studies revealed abnormalities of neuronal cytoskeletal protein in abnormal neuronal cells of NMD.
METHODS
We performed immunohistochemical staining for neurofilament protein (NF) subtypes, one of the neuronal cytoskeletal proteins, and investigated the staining pattern of specific cells in each grade of NMD.
RESULTS
NF-L was more intensely labeled in perikarya, dendrites, and axons of normal or small sized dysplastic neurons, cytomegalic neurons, and balloon cells than of normal-looking neurons. Furthermore, positive reaction was more intense in high-grade lesion. NF-H and NF-M were mainly positive in the axons of gray and white matter and weakly positive in a few cytomegalic neurons and some balloon cells.
CONCLUSION
NF-L is a better marker than NF-H and NF-M for the detection of normal or small sized dysplastic neurons, cytomegalic neurons, and balloon cells and for grading of NMD.

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