Journal of Pathology and Translational Medicine

Original Articles

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma: Sun Ah Shin, Hee Young Na, Ji Young Choe, Doohyun Chung, Mira Park, Sohee Oh, Ji Eun Kim; J Pathol Transl Med. 2018;52(6):357-362. Published online October 4, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.13

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Background
The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.
Methods
Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.
Results
A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.
Conclusions
Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

Citations

Citations to this article as recorded by

Prognostic implications of the immunohistochemical expression of perilipin 1 and adipophilin in high-grade liposarcoma
Kengo Kawaguchi, Kenichi Kohashi, Taro Mori, Hidetaka Yamamoto, Takeshi Iwasaki, Izumi Kinoshita, Yosuke Susuki, Hiroshi Furukawa, Makoto Endo, Yoshihiro Matsumoto, Yasuharu Nakashima, Yoshinao Oda
Journal of Clinical Pathology.2024; 77(10): 676. CrossRef
Prognostic and clinicopathologic significance of PLIN2 in cancers: A systematic review with meta-analysis
Ming-Lin Li, Han-Yong Luo, Zi-Wei Quan, Le-Tian Huang, Jia-He Wang
The International Journal of Biological Markers.2023; 38(1): 3. CrossRef
Novel prognostication biomarker adipophilin reveals a metabolic shift in uveal melanoma and new therapeutic opportunities
Maisoon Matareed, Eleftheria Maranou, Saara A Koskela, Arfa Mehmood, Helen Kalirai, Sarah E Coupland, Carlos R Figueiredo
The Journal of Pathology.2023; 260(2): 203. CrossRef
Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis
Masakazu Fujimoto, Ibu Matsuzaki, Kazuchika Nishitsuji, Yuki Yamamoto, Daisuke Murakami, Takanori Yoshikawa, Ayaka Fukui, Yuuki Mori, Masaru Nishino, Yuichi Takahashi, Yoshifumi Iwahashi, Kenji Warigaya, Fumiyoshi Kojima, Masatoshi Jinnin, Shin-ichi Murat
Laboratory Investigation.2020; 100(5): 727. CrossRef
The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma
Hideaki Hirai, Yuichiro Tada, Masato Nakaguro, Daisuke Kawakita, Yukiko Sato, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Soichiro Takase, Takuro Okada, Hiro
Virchows Archiv.2020; 477(2): 291. CrossRef

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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Abstract PDF

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 Expression of Hypoxia Inducible Factor-1alpha and Its Correlation with the Expressions of Cyclin A1 and Cyclin B1 and the Clinicopathologic Factors of Uterine Cervical Carcinoma.: Ju Yeon Pyo, Jae Ho Cho, Hyunki Kim, Jong Pil Park, Young Tae Kim, Nam Hoon Cho; Korean J Pathol. 2009;43(1):13-19.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.13

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Abstract PDF: BACKGROUND
Hypoxia inducible factor-1alpha(HIF-1alpha) is a transcription factor for various target genes that are involved in adapting cells to hypoxia. It promotes cell proliferation and survival via modulation of such cell cycle regulators such as cyclin A1 and cyclin B1 in response to hypoxia. This is associated with local failure of radiotherapy, which renders a poor prognosis for cervical carcinoma.
METHODS
Using the tissue histologic sections and a tissue microarray of the archived biopsy and surgical specimens of uterine cervical carcinoma from 57 patients who were treated with radiation therapy alone, we performed immunohistochemical staining for HIF-1alpha and cyclin A1 and B1 to evaluate the correlations between the expressions of these proteins in tumors and the clinicopathologic parameters associated with the prognosis.
RESULTS
The large tumor cell nests and invasive front margins of the tumors showed comparatively intense immunoreactivity of HIF-1alpha. There was no significant correlation between the HIF-1alpha, cyclin A1 and cyclin B1 expressions and the clinicopathologic factors.
CONCLUSIONS
The HIF-1alpha expression showed marked intra-tumoral heterogeneity. The HIF-1alpha expression is neither a powerful predictor of resistance to radiotherapy nor is it a poor prognostic marker in cervical carcinoma patients who are treated with radiotherapy. The expressions of cyclin A1 and cyclin B1 are neither independently associated with the response of radiation therapy nor are they associated with the prognostic parameters of uterine cervical carcinoma.

Osteopontin Expression and Its Prognostic Significances in Human Renal Cell Carcinoma.: Hee Yeon Hong, Hyang Lan Lee, Tae Sook Kim, Ghil Suk Yoon; Korean J Pathol. 2006;40(3):225-230.

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Abstract PDF: BACKGROUND
Osteopontin (OPN) is a glycoprotein and it participates in cell-cell and cell-matrix interactions. In vitro studies suggest that the OPN expression is associated with tumor metastasis, and especially with the metastasis of osteotropic tumors originating in breast, prostate and lungs. Since no human tissue study has suggested the means by which OPN participates in the tumorigenesis, angiogenesis, progression and metastasis of renal cell carcinoma (RCC), we evaluated the expression and prognostic significance of OPN in RCC.
METHODS
Immunohistochemistry was performed with using the primary antibody for OPN on the archival paraffin-embedded tissue microarray specimens from 51 RCC patients who underwent radical or simple nephrectomy.
RESULTS
In the normal kidney specimens, OPN was expressed in a few compressed distal tubules adjacent to the RCCs. In RCCs, the OPN expression was elevated in larger tumors (p<0.05) and in the tumor with low microvessel density (p<0.01). In the present study, univariate analysis indicated that stage, tumor size, lymph node and distant organ metastasis are significant prognostic factors for disease free survival (DFS) in RCC patients (p<0.01), but OPN is not (p=0.0661). Multivariate analysis indicated lymph node metastasis is the independent prognostic indicator of DFS (p<0.05).
CONCLUSION
Though this study has statistical limitations, these results suggest OPN plays a role in tumor progression and metastasis and it may act as a potential prognostic indicator to predict the prognosis of RCC patients.

Expression of Hypoxia Inducible Factor-1alpha in Invasive Squamous Cell Carcinoma of Uterine Cervix Treated by Radiotherapy.: Kyung Ja Lee, Min Sun Cho, Seung Cheol Kim, Hae Sung Moon, Hyesook Park, Shi Nae Lee, Sun Hee Sung, Ki Nam Shim, Kyung Eun Lee, Sung Ae Jung, Kwon Yoo, Hae Young Park, Soo Yeun Park, Eun Sun Yoo, Hyun Suk Suh; Korean J Pathol. 2005;39(5):307-312.

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Abstract PDF: BACKGROUND
Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia, and this is associated with reduced radiosensitivity. Furthermore, HIF-1alpha can increase a tumor's aggressiveness by promoting neoangiogenesis, cell proliferation and survival, and invasion.
METHODS
The expression of HIF-1alpha was was investigated by performing immunohistochemistry on the cervical tissue specimens obtained from 57 patients who had received radiotherapy combined with or without chemotherapy for stages I-III cervical squamous cell carcinoma. The staining results were compared with anemia, the stage, the radiotherapy response and patient survival by univariate and multivariate analysis.
RESULTS
In 57 patients, the expression of HIF-1alpha was seen in the tissue specimens of 46 patients (81.7%). Among them, 25 (54.3%), 14 (30.4%), and 7 (15.2%) of the patients' tissue specimens showed weak, moderate and strong expressions, respectively. Six patients had a partial response after radiotherapy. Twelve patients (21.1%) died of cervical cancer. The increased expression of HIF-1alpha was significantly associated (p<0.05) with the disease stage and anemia. There were significant positive correlations between the increased expression of HIF-1alpha and the poor response after radiotherapy and the patients' survival.
CONCLUSIONS
The present result suggests that the overexpression of HIF-1alpha in the uterine cervix could be used as a prognostic indicator for the patients treated with radiotherapy.

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