VSTM2A Overexpression is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney

Lisha Wang, Yuping Zhang, Ying Bei Chen, Stephanie L. Skala, Hikmat A. Al-Ahmadie, Xiaoming Wang, Xuhong Cao, Brendan A. Veeneman, Jin Chen, Marcin Cieślik, Yuanyuan Qiao, Fengyun Su, Pankaj Vats, Javed Siddiqui, Hong Xiao, Evita T. Sadimin, Jonathan I. Epstein, Ming Zhou, Ankur R. Sangoi, Kiril TrpkovAdeboye O. Osunkoya, Giovanna A. Giannico, Jesse K. McKenney, Pedram Argani, Satish K. Tickoo, Victor E. Reuter, Arul M. Chinnaiyan, Saravana M. Dhanasekaran, Rohit Mehra

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 (r2=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 (r2=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.

Original languageEnglish (US)
JournalAmerican Journal of Surgical Pathology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Renal Cell Carcinoma
Biomarkers
Carcinoma
Kidney
In Situ Hybridization
Neoplasms
Area Under Curve
RNA Sequence Analysis
Nephrons
Loop of Henle
Gene Expression
Atlases
ROC Curve
Histology
Genome
RNA
Sensitivity and Specificity
Mutation
Genes

Keywords

  • biomarker
  • IRX5
  • mucinous tubular and spindle cell carcinoma
  • RNA in situ hybridization
  • transcriptome
  • VSTM2A

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

VSTM2A Overexpression is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney. / Wang, Lisha; Zhang, Yuping; Chen, Ying Bei; Skala, Stephanie L.; Al-Ahmadie, Hikmat A.; Wang, Xiaoming; Cao, Xuhong; Veeneman, Brendan A.; Chen, Jin; Cieślik, Marcin; Qiao, Yuanyuan; Su, Fengyun; Vats, Pankaj; Siddiqui, Javed; Xiao, Hong; Sadimin, Evita T.; Epstein, Jonathan I.; Zhou, Ming; Sangoi, Ankur R.; Trpkov, Kiril; Osunkoya, Adeboye O.; Giannico, Giovanna A.; McKenney, Jesse K.; Argani, Pedram; Tickoo, Satish K.; Reuter, Victor E.; Chinnaiyan, Arul M.; Dhanasekaran, Saravana M.; Mehra, Rohit.

In: American Journal of Surgical Pathology, 01.01.2018.

Research output: Contribution to journalArticle

Wang, L, Zhang, Y, Chen, YB, Skala, SL, Al-Ahmadie, HA, Wang, X, Cao, X, Veeneman, BA, Chen, J, Cieślik, M, Qiao, Y, Su, F, Vats, P, Siddiqui, J, Xiao, H, Sadimin, ET, Epstein, JI, Zhou, M, Sangoi, AR, Trpkov, K, Osunkoya, AO, Giannico, GA, McKenney, JK, Argani, P, Tickoo, SK, Reuter, VE, Chinnaiyan, AM, Dhanasekaran, SM & Mehra, R 2018, 'VSTM2A Overexpression is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney', American Journal of Surgical Pathology. https://doi.org/10.1097/PAS.0000000000001150
Wang, Lisha ; Zhang, Yuping ; Chen, Ying Bei ; Skala, Stephanie L. ; Al-Ahmadie, Hikmat A. ; Wang, Xiaoming ; Cao, Xuhong ; Veeneman, Brendan A. ; Chen, Jin ; Cieślik, Marcin ; Qiao, Yuanyuan ; Su, Fengyun ; Vats, Pankaj ; Siddiqui, Javed ; Xiao, Hong ; Sadimin, Evita T. ; Epstein, Jonathan I. ; Zhou, Ming ; Sangoi, Ankur R. ; Trpkov, Kiril ; Osunkoya, Adeboye O. ; Giannico, Giovanna A. ; McKenney, Jesse K. ; Argani, Pedram ; Tickoo, Satish K. ; Reuter, Victor E. ; Chinnaiyan, Arul M. ; Dhanasekaran, Saravana M. ; Mehra, Rohit. / VSTM2A Overexpression is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney. In: American Journal of Surgical Pathology. 2018.
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abstract = "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 (r2=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 (r2=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.",
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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

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