Journal of Pathology and Translational Medicine

Original Articles

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study: Seokhyeon Lee, Bohyun Kim, Minsun Jung, Kyung Chul Moon; J Pathol Transl Med. 2023;57(4):232-237. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.17

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Abstract PDF: Background
Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size.
Methods
We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression.
Results
High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC.
Conclusions
Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma: Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon; J Pathol Transl Med. 2017;51(4):359-364. Published online June 13, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.16

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Background
Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.
Methods
We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.
Results
Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.
Conclusions
Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

Citations

Citations to this article as recorded by

The role of histone methylation in renal cell cancer: an update
Yanguang Hou, Yan Yuan, Yanze Li, Lei Wang, Juncheng Hu, Xiuheng Liu
Molecular Biology Reports.2023; 50(3): 2735. CrossRef
Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis
Ying Dong, Hao Hu, Xuan Zhang, Yunkai Zhang, Xin Sun, Hanlin Wang, Weijuan Kan, Min-jia Tan, Hong Shi, Yi Zang, Jia Li
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
Peng Luo, Yan-dong Zhang, Feng He, Chang-jun Tong, Kai Liu, He Liu, Shi-zhuang Zhu, Jian-zhou Luo, Bing Yuan
Scientific Reports.2022;[Epub] CrossRef
Integration of meta-analysis and supervised machine learning for pattern recognition in breast cancer using epigenetic data
Reza Panahi, Esmaeil Ebrahimie, Ali Niazi, Alireza Afsharifar
Informatics in Medicine Unlocked.2021; 24: 100629. CrossRef
PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks
Ignacio Alonso-de Vega, Maria Cristina Paz-Cabrera, Magdalena B Rother, Wouter W Wiegant, Cintia Checa-Rodríguez, Juan Ramón Hernández-Fernaud, Pablo Huertas, Raimundo Freire, Haico van Attikum, Veronique A J Smits
Nucleic Acids Research.2020; 48(9): 4915. CrossRef
Emerging of lysine demethylases (KDMs): From pathophysiological insights to novel therapeutic opportunities
Sarder Arifuzzaman, Mst Reshma Khatun, Rabeya Khatun
Biomedicine & Pharmacotherapy.2020; 129: 110392. CrossRef
Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview
Tyler S. McCann, Lays M. Sobral, Chelsea Self, Joseph Hsieh, Marybeth Sechler, Paul Jedlicka
Expert Opinion on Therapeutic Targets.2019; 23(4): 267. CrossRef
MiR-221 Promotes Hepatocellular Carcinoma Cells Migration via Targeting PHF2
Yi Fu, Mingyan Liu, Fengxia Li, Li Qian, Ping Zhang, Fengwei Lv, Wenting Cheng, Ruixing Hou
BioMed Research International.2019; 2019: 1. CrossRef
PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors
Stella Pappa, Natalia Padilla, Simona Iacobucci, Marta Vicioso, Elena Álvarez de la Campa, Claudia Navarro, Elia Marcos, Xavier de la Cruz, Marian A. Martínez-Balbás
Proceedings of the National Academy of Sciences.2019; 116(39): 19464. CrossRef
Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia
Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
Epigenomics.2018; 10(1): 59. CrossRef

Immunohistochemical Markers for Metastasis in Clear Cell Renal Cell Carcinoma.: Kyungeun Kim, Cheryn Song, Jae Y Ro, Hanjong Ahn, Yong Mee Cho; Korean J Pathol. 2008;42(2):81-86.

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Abstract PDF: BACKGROUND
Renal cell carcinoma (RCC) is notorious for its high metastatic potential, and 30% of RCC patients present with metastatic disease at the initial presentation and 50% of them will develop metastasis or recurrence after radical surgery.
METHODS
In an attempt to identify the best predictive marker(s) for metastasis in patients with clear cell RCCs (CRCCs), we examined the expression patterns of 7 metastasis/prognosis-related markers by constructing a tissue microarray including primary CRCC specimens from 30 metastatic and 60 nonmetastatic CRCCs. The markers we studied were Ki-67, MUC1, CD44s, PTEN, gelsolin, CA9 and p53.
RESULTS
The expressions of Ki-67, PTEN, CD44s, gelsolin and p53 were increased, whereas those of MUC1 and CA9 were decreased in the metastatic CRCCs compared with the non-metastatic CRCCs. The receiver operating characteristic curve-area under the curve (AUC) value of Ki-67 was 0.671, which was the highest among the 7 markers. The optimal cut-off value, sensitivity and specificity of the Ki-67 expression were 1.67%, 86.7% and 41.7%, respectively.
CONCLUSIONS
These results demonstrate that the Ki-67 expression was increased in metastatic CRCCs, and it had the highest predictive value among the 7 markers. This suggests that Ki-67 could be an excellent predictive marker for metastasis in CRCC patients.

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