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Genitourinary cancer
Clear Cell Adenocarcinoma of Urethra: Clinical and Pathologic Implications and Characterization of Molecular Aberrations
Boram Song, Seok Hyun Lee, Jeong Hwan Park, Kyung Chul Moon
Cancer Res Treat. 2024;56(1):280-293.   Published online September 11, 2023
DOI: https://doi.org/10.4143/crt.2023.577
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods
We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results
All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion
Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.

Citations

Citations to this article as recorded by  
  • Urethral clear cell adenocarcinoma in an adult female: A rare case report
    Yacob Sheiferawe Seman, Michael Teklehaimanot Abera, Fadil Nuredin Abrar, Tesfaye Kebede Legesse, Mesfin Asefa Tola, Tsiyon Nigusie Alemu
    Urology Case Reports.2025; 58: 102882.     CrossRef
  • Association between CACNA1D polymorphisms and hypospadias in a southern Chinese population
    Ye He, Binyao Li, Xinying Zhao, Lingling Pan, Yanqing Liu, Chaoting Lan, Fuming Deng, Wen Fu, Yan Zhang, Xiaoyu Zuo
    Journal of Pediatric Urology.2024; 20(3): 438.e1.     CrossRef
  • The L‐type calcium channel CaV1.3: A potential target for cancer therapy
    Xuerun Liu, Boqiang Shen, Jingyi Zhou, Juan Hao, Jianliu Wang
    Journal of Cellular and Molecular Medicine.2024;[Epub]     CrossRef
  • 3,845 View
  • 194 Download
  • 4 Web of Science
  • 3 Crossref
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Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea
Hee Yeon Lee, Ji Hyung Hong, Jae Ho Byun, Hee-Jun Kim, Sun Kyung Baek, Jin Young Kim, Ki Hyang Kim, Jina Yun, Jung A Kim, Kwonoh Park, Hyo Jin Lee, Jung Lim Lee, Young-Woong Won, Il Hwan Kim, Woo Kyun Bae, Kyong Hwa Park, Der-Sheng Sun, Suee Lee, Min-Young Lee, Guk Jin Lee, Sook Hee Hong, Yun Hwa Jung, Ho Jung An
Cancer Res Treat. 2020;52(1):277-283.   Published online July 12, 2019
DOI: https://doi.org/10.4143/crt.2019.292
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage.
Materials and Methods
Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected.
Results
Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence.
Conclusion
Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

Citations

Citations to this article as recorded by  
  • Ovarian clear cell carcinoma: open questions on the management and treatment algorithm
    Roberta Rosso, Margherita Turinetto, Fulvio Borella, Nicolas Chopin, Pierre Meeus, Alexandra Lainè, Isabelle Ray-Coquard, Olivia Le Saux, Domenico Ferraioli
    The Oncologist.2025;[Epub]     CrossRef
  • From clinical management to personalized medicine: novel therapeutic approaches for ovarian clear cell cancer
    Zesi Liu, Chunli Jing, Fandou Kong
    Journal of Ovarian Research.2024;[Epub]     CrossRef
  • SOX17 expression in ovarian clear cell carcinoma
    Daichi Kodama, Motoki Takenaka, Chiemi Saigo, Masako Azuma, Yuki Hanamatsu, Masanori Isobe, Tamotsu Takeuchi
    Journal of Ovarian Research.2024;[Epub]     CrossRef
  • Construction of a Prediction Model of Cancer-Specific Survival after Ovarian Clear Cell Carcinoma Surgery
    Mengqi Huang, Li Ling, Yanbo Liu, Yujuan Li
    Clinical and Experimental Obstetrics & Gynecology.2024;[Epub]     CrossRef
  • Patients with stage IA ovarian clear cell carcinoma do not require chemotherapy following surgery
    Li Shuqing, Zhu Zhiling
    Cancer Medicine.2023; 12(6): 6668.     CrossRef
  • Clear cell carcinoma of the ovary and venous thromboembolism: a systematic review and meta-analysis
    Hamidreza Didar, Farah Farzaneh, Hanieh Najafiarab, Kosar Namakin, Kimiya Gohari, Ali Sheidaei, Sepehr Ramezani
    Current Medical Research and Opinion.2023; 39(6): 901.     CrossRef
  • The Significance of Radiotherapy in Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis
    Yuan Zhuang, Hua Yang
    Cancer Control.2023;[Epub]     CrossRef
  • Clinical perspectives of rare ovarian tumors: clear cell ovarian cancer
    Satoe Fujiwara
    Japanese Journal of Clinical Oncology.2023; 53(8): 664.     CrossRef
  • Application of precision medicine based on next-generation sequencing and immunohistochemistry in ovarian cancer: a real-world experience
    Yoo-Na Kim, Yun Soo Chung, Ji Hyun Lee, Eunhyang Park, Seung-Tae Lee, Sunghoon Kim, Jung-Yun Lee
    Journal of Gynecologic Oncology.2023;[Epub]     CrossRef
  • Characteristics and Prognosis of Ovarian Pure Clear Cell Carcinoma: A Retrospective Experience of 136 Patients
    Yang Gao, Wei Ding, Pengpeng Qu
    Clinical and Experimental Obstetrics & Gynecology.2023;[Epub]     CrossRef
  • A clearer view on ovarian clear cell carcinoma
    Aglaja De Pauw, Eline Naert, Koen Van de Vijver, Tummers Philippe, Katrien Vandecasteele, Hannelore Denys
    Acta Clinica Belgica.2022; 77(4): 792.     CrossRef
  • Friend or foe? The prognostic role of endometriosis in women with clear cell ovarian carcinoma. A UK population-based cohort study
    Anastasios Tranoulis, Felicia Helena Buruiana, Bindiya Gupta, Audrey Kwong, Aarti Lakhiani, Jason Yap, Janos Balega, Kavita Singh
    Archives of Gynecology and Obstetrics.2022; 305(5): 1279.     CrossRef
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    Peng Chen, Chi-Yuan Zhang
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Clinical analysis and literature review of a case of ovarian clear cell carcinoma with PIK3CA gene mutation: A case report
    Abdulkarim Mohamed Farah, Shiyu Gu, Yan Jia
    Medicine.2022; 101(37): e30666.     CrossRef
  • Clear cell carcinoma of the ovary: a clinical and molecular perspective
    Yasushi Iida, Aikou Okamoto, Robert L Hollis, Charlie Gourley, C Simon Herrington
    International Journal of Gynecological Cancer.2021; 31(4): 605.     CrossRef
  • Clinical characteristics and prognosis of ovarian clear cell carcinoma: a 10-year retrospective study
    Chenchen Zhu, Jing Zhu, Lili Qian, Hanyuan Liu, Zhen Shen, Dabao Wu, Weidong Zhao, Weihua Xiao, Ying Zhou
    BMC Cancer.2021;[Epub]     CrossRef
  • The oncological outcome of the patients with ovarian clear cell cancer: Platinum-based adjuvant chemotherapy is not suitable
    Caner ÇAKIR, Fatih KILIÇ, Çiğdem KILIÇ, Dilek YÜKSEL, Vakkas KORKMAZ, Günsu KİMYON CÖMERT, Osman TÜRKMEN, Taner TURAN
    Journal of Surgery and Medicine.2021; 5(8): 1.     CrossRef
  • Development and validation of Nomograms for predicting overall survival and Cancer-specific survival in patients with ovarian clear cell carcinoma
    Qian Chen, Shu Wang, Jing-He Lang
    Journal of Ovarian Research.2020;[Epub]     CrossRef
  • 9,008 View
  • 421 Download
  • 22 Web of Science
  • 18 Crossref
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Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study
Hee Seung Kim, Hwa-Young Choi, Maria Lee, Dong Hoon Suh, Kidong Kim, Jae Hong No, Hyun Hoon Chung, Yong Beom Kim, Yong Sang Song
Cancer Res Treat. 2016;48(1):250-258.   Published online March 6, 2015
DOI: https://doi.org/10.4143/crt.2014.324
AbstractAbstract PDFPubReaderePub
Purpose
We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC).
Materials and Methods
The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes.
Results
Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted noncomplete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers.
Conclusion
CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

Citations

Citations to this article as recorded by  
  • Ovarian clear cell carcinoma: open questions on the management and treatment algorithm
    Roberta Rosso, Margherita Turinetto, Fulvio Borella, Nicolas Chopin, Pierre Meeus, Alexandra Lainè, Isabelle Ray-Coquard, Olivia Le Saux, Domenico Ferraioli
    The Oncologist.2025;[Epub]     CrossRef
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    Justina Omoikhefe Alegbeleye, Celestine Osita John
    Indian Journal of Obstetrics and Gynecology Research.2024; 11(1): 17.     CrossRef
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    Bing-Qian Tian, Shu-Wen Wang, Jing-Ying Xu, San-Gang Wu, Juan Zhou
    Frontiers in Oncology.2024;[Epub]     CrossRef
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    Jaime Espinós, José Manuel Aramendía, Antonio González-Martín, Marta Santisteban, Luisa Sánchez, Ángel Vizcay, José Ángel Mínguez, Juan Luis Alcázar
    Clinical and Translational Oncology.2024; 26(12): 3211.     CrossRef
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    Journal of Ovarian Research.2023;[Epub]     CrossRef
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    Journal of Ovarian Research.2023;[Epub]     CrossRef
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    Cancers.2023; 15(14): 3607.     CrossRef
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    洁 严
    Advances in Clinical Medicine.2023; 13(11): 17362.     CrossRef
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    Fatemeh Tabatabaei, Hossein Tahernia, Arshin Ghaedi, Aida Bazrgar, Shokoufeh Khanzadeh
    BMC Women's Health.2023;[Epub]     CrossRef
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    Majalah Obstetri & Ginekologi.2023; 31(3): 117.     CrossRef
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    Huimin Bai, Guisha Sha, Meizhu Xiao, Huiqiao Gao, Dongyan Cao, Jiaxin Yang, Jie Chen, Yue Wang, Zhenyu Zhang, Keng Shen
    Oncotarget.2016; 7(13): 15566.     CrossRef
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    Ghazala Khan, Suzanne E. Brooks, Ken I. Mills, Barbara-Ann Guinn
    Biomarkers in Cancer.2015; 7: BIC.S28378.     CrossRef
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  • 46 Crossref
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