Journal of Pathology and Translational Medicine

Original Article

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.

Case Study

Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient: Bohyun Kim, Han-Kwang Yang, Woo Ho Kim; J Pathol Transl Med. 2018;52(2):126-129. Published online December 21, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.16

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A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.

Citations

Citations to this article as recorded by

A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid
Suk Ki Park, Moon Won Lee, In Sub Han, Young Joo Park, Sung Yong Han, Joon Woo Park, Bong Eun Lee, Gwang Ha Kim, Sang Soo Kim
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2019; 19(1): 65. CrossRef

Original Articles

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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Abstract PDF

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

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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
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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

Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma: Gilhyang Kim, Yul Ri Chung, Bohyun Kim, Boram Song, Kyung Chul Moon; J Pathol Transl Med. 2016;50(6):436-441. Published online October 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.12

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Abstract PDF

Background
Human epidermal growth factor receptor 2 (HER2) is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC) has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA) criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and compare their prognostic significance in UUTUC.
Methods
HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC) using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+) and high (2+, 3+) groups.
Results
Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001). The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004), but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161) in cancer-specific survival.
Conclusions
HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

Citations

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A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients
Jianjun Ye, Xinyang Liao, Yu Qiu, Qiang Wei, Yige Bao
Tumori Journal.2024; 110(1): 25. CrossRef
ERBB2 Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma
Annette Zimpfer, Said Kdimati, Melanie Mosig, Henrik Rudolf, Heike Zettl, Andreas Erbersdobler, Oliver W. Hakenberg, Matthias Maruschke, Björn Schneider
Cancers.2023; 15(9): 2414. CrossRef
Near-Infrared Photoimmunotherapy (NIR-PIT) in Urologic Cancers
Hiroshi Fukushima, Baris Turkbey, Peter A. Pinto, Aki Furusawa, Peter L. Choyke, Hisataka Kobayashi
Cancers.2022; 14(12): 2996. CrossRef
Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication
Manuela Costantini, Carla Azzurra Amoreo, Liborio Torregrossa, Greta Alì, Enrico Munari, Carmen Jeronimo, Rui Henrique, Sara Petronilho, Umberto Capitanio, Roberta Lucianò, Nazareno Suardi, Maria Teresa Landi, Umberto Anceschi, Aldo Brassetti, Vito Michel
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