A Nomogram Based on TFE3 IHC Results and Clinical Factors As a Preliminary Screening Scheme for TFE3-rearranged Renal Cell Carcinoma

Overview

Journal Cancer Med

Specialty Oncology

Date 2024 Mar 13

PMID 38477529

Authors

Pengju Li

Quanhui Xu

Minyu Chen

Jiangquan Zhu

Yinghan Wang

Mukhtar A Mumin

Kangbo Huang

Zeying Jiang

Hui Liang

Qiong Deng

Zhu Wang

Bing Liao

Wenfang Chen

Yun Cao

Jiazheng Cao

Junhang Luo

Affiliations

Soon will be listed here.

Abstract

Background: TFE3 immunohistochemistry (TFE3-IHC) is controversial in the diagnosis of TFE3-rearranged renal cell carcinoma (TFE3-rearranged RCC). This study is to investigate the accuracy and sensitivity of IHC and establish a predictive model to diagnose TFE3-rearranged RCC.

Methods: Retrospective analysis was performed by collecting IHC and fluorescence in situ hybridization (FISH) results from 228 patients. IHC results were evaluated using three scoring systems. Scoring system 1 is graded based on nuclear staining intensity, scoring system 2 is graded based on the percentage of stained tumor cell nuclei, and scoring system 3 is graded based on both the nuclear staining intensity and the percentage. We collected patients' IHC results and clinical information. Important variables were screened based on univariate logistic regression analysis. Then, independent risk factors were established through multivariate logistic regression, and a nomogram model was constructed. The model was validated in internal test set and external validation set. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) were generated to assess discriminative ability of the model.

Results: The accuracy of IHC based on three scoring systems were 0.829, 0.772, and 0.807, respectively. The model included four factors including age, gender, lymph node metastasis and IHC results. Area under the curve (AUC) values were 0.935 for the training set, 0.934 for the internal test set, 0.933 for all 228 patients, and 0.916 for the external validation set.

Conclusions: TFE3 IHC has high accuracy in the diagnosis of TFE3-rearranged RCC. Clinical information such as age and lymph node metastasis are independent risk factors, which can be used as a supplement to the results of TFE3 IHC. This study confirms the value of IHC in the diagnosis of TFE3-rearranged RCC. The accuracy of the diagnosis can be improved by incorporating IHC with other clinical risk factors.

Citing Articles

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PMID: 38960941 PMC: 11222356. DOI: 10.1007/s12672-024-01140-8.

A nomogram based on TFE3 IHC results and clinical factors as a preliminary screening scheme for TFE3-rearranged renal cell carcinoma.

Li P, Xu Q, Chen M, Zhu J, Wang Y, Mumin M Cancer Med. 2024; 13(5):e6813.

PMID: 38477529 PMC: 10935875. DOI: 10.1002/cam4.6813.

References

Sukov W, Hodge J, Lohse C, Leibovich B, Thompson R, Pearce K . TFE3 rearrangements in adult renal cell carcinoma: clinical and pathologic features with outcome in a large series of consecutively treated patients. Am J Surg Pathol. 2012; 36(5):663-70. DOI: 10.1097/PAS.0b013e31824dd972. View

Sidhar S, Clark J, Gill S, Hamoudi R, Crew A, Gwilliam R . The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum Mol Genet. 1996; 5(9):1333-8. DOI: 10.1093/hmg/5.9.1333. View

Sharain R, Gown A, Greipp P, Folpe A . Immunohistochemistry for TFE3 lacks specificity and sensitivity in the diagnosis of TFE3-rearranged neoplasms: a comparative, 2-laboratory study. Hum Pathol. 2019; 87:65-74. DOI: 10.1016/j.humpath.2019.02.008. View

Patel R, Downs-Kelly E, Weiss S, Folpe A, Tubbs R, Tuthill R . Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma. Mod Pathol. 2005; 18(12):1585-90. DOI: 10.1038/modpathol.3800503. View

Yang B, Duan H, Cao W, Guo Y, Liu Y, Sun L . Xp11 translocation renal cell carcinoma and clear cell renal cell carcinoma with TFE3 strong positive immunostaining: morphology, immunohistochemistry, and FISH analysis. Mod Pathol. 2019; 32(10):1521-1535. DOI: 10.1038/s41379-019-0283-z. View

Haudebourg J, Hoch B, Fabas T, Burel-Vandenbos F, Carpentier X, Amiel J . A novel case of t(X;1)(p11.2;p34) in a renal cell carcinoma with TFE3 rearrangement and favorable outcome in a 57-year-old patient. Cancer Genet Cytogenet. 2010; 200(2):75-8. DOI: 10.1016/j.cancergencyto.2010.03.011. View

Antic T, Taxy J, Alikhan M, Segal J . Melanotic Translocation Renal Cell Carcinoma With a Novel ARID1B-TFE3 Gene Fusion. Am J Surg Pathol. 2017; 41(11):1576-1580. DOI: 10.1097/PAS.0000000000000927. View

Lee H, Shin D, Noh G, Kim Y, Kim A, Shin N . Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11 translocation RCC: comparison of three different diagnostic methods. Oncotarget. 2017; 8(19):30756-30765. PMC: 5458165. DOI: 10.18632/oncotarget.16481. View

Downs-Kelly E, Goldblum J, Patel R, Weiss S, Folpe A, Mertens F . The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms. Am J Surg Pathol. 2007; 32(1):8-13. DOI: 10.1097/PAS.0b013e3181578d5a. View

10.

Li P, Xu Q, Chen M, Zhu J, Wang Y, Mumin M . A nomogram based on TFE3 IHC results and clinical factors as a preliminary screening scheme for TFE3-rearranged renal cell carcinoma. Cancer Med. 2024; 13(5):e6813. PMC: 10935875. DOI: 10.1002/cam4.6813. View

11.

Dai C, Sheng R, Ding Y, Yang M, Hou J, Zhou J . Magnetic resonance imaging findings of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in adults: a pilot study. Abdom Radiol (NY). 2018; 44(1):209-217. DOI: 10.1007/s00261-018-1703-0. View

12.

Kuthi L, Somoracz A, Micsik T, Jenei A, Hajdu A, Sejben I . Clinicopathological Findings on 28 Cases with XP11.2 Renal Cell Carcinoma. Pathol Oncol Res. 2020; 26(4):2123-2133. PMC: 7471254. DOI: 10.1007/s12253-019-00792-0. View

13.

Green W, Yonescu R, Morsberger L, Morris K, Netto G, Epstein J . Utilization of a TFE3 break-apart FISH assay in a renal tumor consultation service. Am J Surg Pathol. 2013; 37(8):1150-63. DOI: 10.1097/PAS.0b013e31828a69ae. View

14.

Humphrey P, Moch H, Cubilla A, Ulbright T, Reuter V . The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016; 70(1):106-119. DOI: 10.1016/j.eururo.2016.02.028. View

15.

Argani P, Antonescu C, Couturier J, Fournet J, Sciot R, Debiec-Rychter M . PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol. 2002; 26(12):1553-66. DOI: 10.1097/00000478-200212000-00003. View

16.

Rakheja D, Kapur P, Tomlinson G, Margraf L . Pediatric renal cell carcinomas with Xp11.2 rearrangements are immunoreactive for hMLH1 and hMSH2 proteins. Pediatr Dev Pathol. 2005; 8(6):615-20. DOI: 10.1007/s10024-005-0148-y. View

17.

Argani P, Lal P, Hutchinson B, Lui M, Reuter V, Ladanyi M . Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003; 27(6):750-61. DOI: 10.1097/00000478-200306000-00005. View

18.

Qin K, Fu X . [Research Progress in Imaging-based Diagnosis of Benign and Malignant  Enlarged Lymph Nodes in Non-small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2023; 26(1):31-37. PMC: 9987091. DOI: 10.3779/j.issn.1009-3419.2023.101.01. View

19.

Kim S, Choi Y, Jeong H, Lee K, Chae J, Moon K . Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma. Virchows Arch. 2011; 459(3):299-306. DOI: 10.1007/s00428-011-1127-5. View

20.

Perlman E . Pediatric Renal Cell Carcinoma. Surg Pathol Clin. 2010; 3(3):641-651. PMC: 2967736. DOI: 10.1016/j.path.2010.06.011. View