TY - JOUR
T1 - VSTM2A Overexpression Is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney
AU - Wang, Lisha
AU - Zhang, Yuping
AU - Chen, Ying Bei
AU - Skala, Stephanie L.
AU - Al-Ahmadie, Hikmat A.
AU - Wang, Xiaoming
AU - Cao, Xuhong
AU - Veeneman, Brendan A.
AU - Chen, Jin
AU - Cieślik, Marcin
AU - Qiao, Yuanyuan
AU - Su, Fengyun
AU - Vats, Pankaj
AU - Siddiqui, Javed
AU - Xiao, Hong
AU - Sadimin, Evita T.
AU - Epstein, Jonathan I.
AU - Zhou, Ming
AU - Sangoi, Ankur R.
AU - Trpkov, Kiril
AU - Osunkoya, Adeboye O.
AU - Giannico, Giovanna A.
AU - McKenney, Jesse K.
AU - Argani, Pedram
AU - Tickoo, Satish K.
AU - Reuter, Victor E.
AU - Chinnaiyan, Arul M.
AU - Dhanasekaran, Saravana M.
AU - Mehra, Rohit
N1 - Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Our recent study revealed recurrent chromosomal losses and somatic mutations of genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and the Knepper data set of microdissected rat nephrons. We identified VSTM2A and IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then assessed their expression by RNA in situ hybridization (ISH) in 113 tumors, including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2 unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and specificity were calculated as the area under the receiver operating characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA sequencing strongly correlated with VSTM2A ISH score (r 2 =0.81, P=0.00016). The majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A. IRX5, nominated as a lineage-specific biomarker, showed moderate to high expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by RNA sequencing strongly correlated with IRX5 ISH score (r 2 =0.69, P=0.00291). VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC: 87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors with overlapping histology. Furthermore, our results suggest MTSCC displays an overlapping phenotypic expression pattern with the loop of Henle region of normal nephrons.
AB - Our recent study revealed recurrent chromosomal losses and somatic mutations of genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and the Knepper data set of microdissected rat nephrons. We identified VSTM2A and IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then assessed their expression by RNA in situ hybridization (ISH) in 113 tumors, including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2 unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and specificity were calculated as the area under the receiver operating characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA sequencing strongly correlated with VSTM2A ISH score (r 2 =0.81, P=0.00016). The majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A. IRX5, nominated as a lineage-specific biomarker, showed moderate to high expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by RNA sequencing strongly correlated with IRX5 ISH score (r 2 =0.69, P=0.00291). VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC: 87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors with overlapping histology. Furthermore, our results suggest MTSCC displays an overlapping phenotypic expression pattern with the loop of Henle region of normal nephrons.
KW - IRX5
KW - RNA in situ hybridization
KW - VSTM2A
KW - biomarker
KW - mucinous tubular and spindle cell carcinoma
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85054473283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054473283&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001150
DO - 10.1097/PAS.0000000000001150
M3 - Article
C2 - 30285995
AN - SCOPUS:85054473283
SN - 0147-5185
VL - 42
SP - 1571
EP - 1584
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 12
ER -