Journal of Pathology and Translational Medicine

Original Articles

Post-mortem assessment of vimentin expression as a biomarker for renal tubular regeneration following acute kidney injury: Juan Carlos Alvarez Moreno, Hisham F. Bahmad, Christopher A. Febres-Aldana, Andrés Pirela, Andres Azuero, Ali Salami, Robert Poppiti; J Pathol Transl Med. 2021;55(6):369-379. Published online October 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.03

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Background
Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E.
Methods
We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression.
Results
Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression.
Conclusions
In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.

Citations

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Characterization of macrophages in ischemia–reperfusion injury-induced acute kidney injury based on single-cell RNA-Seq and bulk RNA-Seq analysis
Qin Wang, Yuxing Liu, Yan Zhang, Siyuan Zhang, Meifang Zhao, Zhangzhe Peng, Hui Xu, Hao Huang
International Immunopharmacology.2024; 130: 111754. CrossRef
Renal tubular necrosis associated with anagrelide administration: a case report
Atsushi Sawase, Mineaki Kitamura, Misato Morimoto, Haruka Fukuda, Tadashi Uramatsu, Eisuke Katafuchi, Hiroshi Yamashita, Toshiyuki Nakayama, Hiroshi Mukae, Tomoya Nishino
CEN Case Reports.2024;[Epub] CrossRef
Morin attenuates sepsis-induced acute kidney injury by regulating inflammatory responses, oxidative stress and tubular regeneration (morin and sepsis-induced acute kidney injury)
Aya M. Shehata, Nagui H. Fares, Basma H. Amin, Asmaa A. Mahmoud, Yomna I. Mahmoud
Environmental Toxicology and Pharmacology.2024; 111: 104543. CrossRef

The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma: Kyu Ho Kim, Lucia Kim, Suk Jin Choi, Jee Young Han, Joon Mee Kim, Young Chae Chu, Young-Mo Kim, In Suh Park, Joo Han Lim; Korean J Pathol. 2014;48(4):263-269. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.263

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Abstract PDF

Background

Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis.

Results

The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival.

Conclusions

These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

Citations

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Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma
Yuxi Cheng, Zhengzheng Song, Xiaodan Fang, Zhangui Tang
Clinical Epigenetics.2024;[Epub] CrossRef
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Samar M. Abdel Raouf, Taiseer R. Ibrahim, Lobna A. Abdelaziz, Mohamed I. Farid, Salem Y Mohamed
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HOXB5 acts as an oncogenic driver in head and neck squamous cell carcinoma via EGFR/Akt/Wnt/β-catenin signaling axis
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Si-Hyong Jang, Jong Eun Lee, Mee-Hye Oh, Ji-Hye Lee, Hyun Deuk Cho, Kyung-Ju Kim, Sung Yong Kim, Sun Wook Han, Han Jo Kim, Sang Byung Bae, Hyun Ju Lee
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Loss of E-cadherin and Acquisition of Vimentin in Epithelial-Mesenchymal Transition are Noble Indicators of Uterine Cervix Cancer Progression: Na-Hye Myong; Korean J Pathol. 2012;46(4):341-348. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.341

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) has been known to play a key role in the stromal invasion of carcinoma in situ (CIS) lesion. Loss of E-cadherin and acquisition of vimentin are two critical steps in EMT, that are induced by Snail-1 upregulation associated with overexpression of epidermal growth factor receptor (EGFR). However, roles of EMT-related proteins in human cervical tissues have not been fully elucidated. In this study, we investigated the immunoexpressions of EMT-related proteins in CIS, microinvasive squamous cell carcinoma (SCC), and invasive SCC to demonstrate their key roles in tumor progression.

Methods

Eighty one CIS, 17 microinvasive, and 21 invasive SCC cases were immunostained with primary antibodies for Snail-1, EGFR, E-cadherin, and vimentin on paraffin-embedded tissue microarray blocks.

Results

EGFR and Snail-1 proteins were highly expressed but the levels were not significantly different between the three groups. However, loss of E-cadherin and acquisition of vimentin were proven to occur significantly higher in microinvasive and invasive SCC cases than in CIS.

Conclusions

E-cadherin and vimentin were found to be two useful indicators of EMT in evaluating stromal invasion of CIS. However, it was not demonstrated for Snail-1 and EGFR proteins to play any key role in the progression of cervix cancer.

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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.

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Abstract PDF: We performed a histopathologic and immunohistochemical study of 23 cases of surgically resected large cell undifferentiated carcinoma(LCUC) of the lung. The relative incidence of LCUC was 7.6% among the total resected cases of primary lung cancer over 7 years(1987-1993). The mean age of the patients was 56 years and 21 cases were male. The mean size of the mass was 5 cm and 11 cases were located peripherally. According to the histologic features, LCUC could be divided into three groups: squamous cell carcinoma-like(6 cases), adenocarcinoma-like(13 cases), and small cell carcinoma-like(4 cases) groups. The histologic differences were related to the variations of the immunohistochemical properties, but there were no differences in prognosis among these groups. Immunoreactivity to cytokeratin(CAM 5.2) was demonstrated in 22/23(96%). Carcinoembryonic antigen was positive in 13/23(57%). Neuron specific enolase and chromogranin were positive in 11/23(48%) and 5/23(22%), respectively. Vimentin was seen in 11/23(48%). From these observations, we could subclassify them by their immunologic phenotypes; exocrine features in 6/23(26%), neuroendocrine(NE) features in 4/23(17%), both exocrine and NE phenotypes in 7/23(30%), and 6 cases(26%) showed neither phenotype. The group with NE features showed a worse prognosis(P<0.05) and immunoreactivity for vimentin was also related to a worse prognosis(P<0.05). These findings imply that the immunohistochemical properties of LCUC are closely related to the histopathologic features. The groups, subdivided by histology and immunoreactivity, showed no prognostic difference except for the NE differentiation and reaction for vimentin.

Relationship between Vimentin Expression and Progression of Uterine Cervix Epithelial Neoplasms.: Sung Chul Lim, Keun Hong Kee, Hyun Jong Park; Korean J Pathol. 1998;32(9):663-669.

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Abstract: Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but the evidence of the aberrant expression of vimentin in epithelial cancer cells suggests that the vimentin expression might be related to local invasiveness and metastatic potential. There have been a few previous studies on the vimentin expression in human cervical carcinogenesis using in vivo and in vitro models. We examined the immunohistochemical vimentin expression in various squamous epithelial neoplasms of the uterine cervix, including the cervical intraepithelial neoplasia group (n=25), the microinvasive squamous cell carcinoma group (n=15), the invasive squamous cell carcinoma group (n=15) and the metastatic squamous cell carcinoma group (n=8). Vimentin positivity was significantly higher in the invasive than in the intraepithelial group, and in the cases with lymph node metastasis than in those without metastasis, suggesting a relationship between the vimentin expression and progression of the uterine cervical epithelial tumors.

Case Report

Primary Malignant Fibrous Histiocytoma of the Liver: A case report.: Bum Kyeong Kim, Kyeong Hee Kim, Hye Jeong Sul, Dae Young Kang; Korean J Pathol. 1999;33(1):48-51.

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Abstract PDF: Malignant fibrous histiocytoma (MFH) of the liver is uncommon, representing less than 1% of the primary malignant lesions of the liver. We report primary MFH of the liver in a 59-year-old woman. The tumor, measuring 9.0 9.0 6.0 cm, was located in the left lobe of the liver. It showed multiple areas of hemorrhage and necrosis. Microscopically, the tumor consisted of plump spindle cells haphazardly arranged in short fascicle and focal storiform pattern. Multiple bizarre giant cells were also noted. Immunohistochemically, many of the tumor cells were positive for vimentin and alpha1-antitrypsin but negative for epithelial markers. Ultrastructurally, the tumor cells showed fibroblastic and histiocytic features.

Original Articles

Expression of Glomerular-Smooth Muscle Actin and Vimentin in Idiopathic Membranous Nephropathy as Prognostic Indicators.: Min Jin Lee, Ok Kyung Kim; Korean J Pathol. 2001;35(1):26-34.

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Abstract PDF: BACKGROUND
The natural history of idiopathic membranous nephropathy (IMN) is heterogeneous with some patients showing spontaneous remission while others show a progressive course leading to end-stage renal failure. We tried to assess quantitatively alpha-smooth muscle actin (alpha-SMA) and vimentin expression as markers to predict the outcome of membranous nephropathy.
METHODS
This study included 24 patients with biopsy proven IMN. We measured the volume of the positive area for alpha-SMA and vimentin within the glomeruli and compared the results with 5 patients in the normal control group. We evaluated glomerular alpha-SMA and vimentin expression in correlation with BUN and serum creatinine level at the time of diagnosis and after treatment.
RESULTS
Glomerular alpha-SMA and vimentin in IMN were higher than in the control group. Glomerular alpha-SMA was significantly higher in progressive IMN than in non-progressive IMN. The glomerular alpha-SMA was sifnificantly correlated with BUN and serum creatinine at last follow-up (p<0.05), but there was no statistically significant correlation at diagnosis. The glomerular vimentin was not different between progressive and non-progressive groups.
CONCLUSION
These data suggest that the expression of glomerular alpha-SMA may be a useful prognostic indicator and may be able to differentiate between patients with membranous nephropathy who respond well to treatment and those who continue to progress.

Vimentin and Survivin Expression Rates as Prognostic Factors in Medulloblastoma.: Jae Yeon Seok, Se Hoon Kim, Yoon Hee Lee, Jieun Kwon, Tai Seung Kim; Korean J Pathol. 2007;41(2):87-94.

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Abstract PDF: BACKGROUND
A medulloblastoma is a primitive neuroepithelial tumor of the cerebellum that occurs in children and metastasizes through the cerebrospinal fluid. It is highly malignant and invasive, and the 5-year survival rate is only 60%. Surgical resection techniques, radiation, and chemotherapy have improved the overall survival but the patients suffer life-long cognitive dysfunctions or endocrine abnormalities as the side effects of treatment. Therefore it is essential to identify prognostic markers to determine the appropriate treatment strategy in order to minimize the side effects.
METHODS
This study evaluated the immunohistochemical differentiation and survival rate with synaptophysin, glial fibrillary acidic protein, epithelial membrane antigen, vimentin and primitive neuroepithelial marker nestin of 55 paraffin-embedded medulloblastomas, using a tissue microarray. The expression of survivin, the apoptotic inhibitor, and the survival rate with regard to the proliferation index of Ki-67 were also investigated.
RESULTS
The group testing positive to vimentin, a mesenchymal differentiation marker, had a worse prognosis and there was a strong correlation between vimentin expression and nestin expression. Patients with a survivin expression rate >35% had a significantly poorer clinical course and there was a correlation between the survivin expression rate and Ki-67 expression rate.
CONCLUSION
In conclusion, vimentin and survivin are negative prognostic markers in medulloblastomas.

Immunohistochemical Staining of Ovarian Tumors.: Young Seak Kim, Yang Seok Chae, In Sun Kim, Seung Yong Paik; Korean J Pathol. 1991;25(1):11-20.

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Abstract PDF: Forty-four ovairan tumors were immunohistochemically studied for the presence of broad-spectrum keratin, vimentin, desin, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and alpha 1-antitrypsin (AAT) in formalin-fixed, paraffin-embedded tissues. 1) Among the common epithelial tumors, all the serous carcinomas (4) expressed keratin and AAT, and one additionally CEA. Six mucinous carcinomas exhibited keratin-positivity in two. One endometrioid carcinoma coexpressed keratin and vimentin as well as AAT, but one clear cell carcinoma expressed only keratin. Keratin-and CEA-positivity in epithelial cell nests and vimentin-positivity in stromal cells were observed in two Brenner tumors. Two undifferentiated carcinomas showed keratin-positivity in one and focal CEA positivity in the other. 2) In sex cord-stromal tumors, four out of six granulsa cell tumors, all four thecomas and three fibromas expressed vimentin, and two granulosa cell tumors and two thecomas showed AAT-positivity. The others were negative. 3) Among germ cell tumors, four dysgerminomas showed focal vimentin-positive cells in two and diffuse staining for AAT. Seven endodermal sinus tumors expressed AAT in all. Additionally, AFP were positive in two and CEA in three out of them. One embryonal carcinoma expressed CEA, AAT and AFP. 4) In four metastatic carcinomas, three exhibited keratin-and CEA-positivity, whereas one exhibited keartin-and vimentin-positivity. All showed AAT-positivity. 5) There was no positive case for desmin among ovarian tumors.

Hemangiopercytoma of the Meninges: The immunohistochemical study for the relationship between hemangiopericytic meningioma and peripheral hemangiopericytoma.: Sun Hee Yoon, Weon Yeong Choi, Sook Nyo Lee, In Sook Lim, Sook Hee Hong; Korean J Pathol. 1990;24(4):502-508.

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Abstract PDF: Hemangiopericycic maningioma is clinically and pathologically similar to peripheral Hemangiopericytoma and now tends to be terned as hemangiopericytoma of central nervous system. The authors studied 3 cases of hemangiopericytic meningioma obtained from 3 patients, 1 case of meningotheliomatous meningioma, angioblastic meningioma and transitional meningioma, and 2 cases of peripheral hemangiopericytoma, which had operated from November 1988 to May 1989 at the department of neurosurgery, Pusan Inje University Hospital. The authors analysed and compared the immunohistochemical finding and light microscopic apearance. The results obtained were summarized as follows; 1) Classic maningioma (meningotheliomatous meningioma, transitional meningioma and angioblastic meningioma) shows reactivity to both EMA and vimentin. 2) Hemangiopercicytic meningioma and peripheral hemangiopericytoma are reactive only to vimentin, so the two tumors are suggested as same type of tumor. 3) One of 3 cases of hemangiopericytic meningioma shows whorling and interlacing bundles of spindle cells, the peculiar light microscopic features of transitional meningioma, suggesting transitional or mixed form of hemangiopericytic meningioma and transitional meningioma.

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