Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers.
OBJECTIVE
The clinical management of small renal masses (SRMs) is challenging since the current methods for distinguishing between benign masses and malignant renal cell carcinomas (RCCs) are frequently inaccurate or inconclusive. In addition, renal cancer subtypes also have different treatments and outcomes. High false negative rates increase the risk of cancer progression and indeterminate diagnoses result in unnecessary and potentially morbid surgical procedures.


METHODS
We built a predictive classification model for kidney tumors using 697 DNA methylation profiles from six different subgroups: clear cell, papillary and chromophobe RCC, benign angiomylolipomas, oncocytomas, and normal kidney tissues. Furthermore, the DNA methylation-dependent classifier has been validated in 272 ex vivo needle biopsy samples from 100 renal masses (71% SRMs).


RESULTS
In general, the results were highly reproducible (89%, n=70) in predicting identical malignant subtypes from biopsies. Overall, 98% of adjacent-normals (n=102) were correctly classified as normal, while 92% of tumors (n=71) were correctly classified malignant and 86% of benign (n=29) were correctly classified benign by this classification model.


CONCLUSIONS
Overall, this study provides molecular-based support for using routine needle biopsies to determine tumor classification of SRMs and support the clinical decision-making.
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Sameer
S
Chopra
Department of Preventive Medicine, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Jie
J
Liu
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mehrdad
M
Alemozaffar
Department of Pathology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Peter W
PW
Nichols
Department of Pathology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Manju
M
Aron
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Daniel J
DJ
Weisenberger
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Clayton K
CK
Collings
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Sumeet
S
Syan
Department of Urology, Loma Linda University, Loma Linda, CA, USA.
Brian
B
Hu
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mihir
M
Desai
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Monish
M
Aron
Department of Radiology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Vinay
V
Duddalwar
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Inderbir
I
Gill
Department of Urology, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Gangning
G
Liang
Department of Preventive Medicine, Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Kimberly D
KD
Siegmund
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001707:Biopsy, Needle; D003198:Computer Simulation; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D055815:Young Adult
D014408:Biomarkers, Tumor
DNA methylation; kidney cancer; small renal mass; tumor classification
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