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VSTM2A Overexpression Is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC)

Lisha Wang1,2, Yuping Zhang1,2, Ying-Bei Chen3

  • 1Michigan Center for Translational Pathology.

The American Journal of Surgical Pathology
|October 5, 2018
PubMed

Insights

Researchers identified VSTM2A and IRX5 as novel biomarkers for mucinous tubular and spindle cell carcinoma (MTSCC). VSTM2A showed high diagnostic accuracy, distinguishing MTSCC from other renal cell carcinomas (RCCs).

Area of Science:

  • Oncology
  • Genomics
  • Biomarker Discovery

Background:

  • Mucinous tubular and spindle cell carcinoma (MTSCC) is a subtype of renal cell carcinoma (RCC).
  • Previous studies indicated genetic alterations in the Hippo pathway in MTSCC.
  • Accurate diagnosis of MTSCC can be challenging due to overlapping histology with other RCC subtypes.

Purpose of the Study:

  • To identify novel cancer-specific and lineage-specific biomarkers for MTSCC.
  • To evaluate the diagnostic efficacy of potential biomarkers in distinguishing MTSCC from other RCCs.
  • To explore the phenotypic expression patterns of MTSCC in relation to normal nephron structures.

Main Methods:

  • Integrative analysis of 907 renal cell carcinoma (RCC) samples and rat nephron data.
  • Identification of VSTM2A and IRX5 as potential biomarkers.
  • Assessment of VSTM2A and IRX5 expression using RNA in situ hybridization (ISH) in 113 tumors.
  • Correlation analysis between RNA sequencing and ISH gene expression data.
  • Calculation of diagnostic accuracy using Area Under the Receiver Operating Characteristics Curve (AUC).

Main Results:

  • VSTM2A and IRX5 were identified as novel cancer-specific and lineage-specific biomarkers for MTSCC.
  • All MTSCC tumors exhibited moderate to high VSTM2A expression (mean ISH score=255), with strong correlation to RNA sequencing data (r²=0.81).
  • Non-MTSCC tumors generally showed negative or low VSTM2A expression.
  • IRX5 also showed moderate to high expression in MTSCC (mean ISH score=140), correlating with RNA sequencing data (r²=0.69).
  • VSTM2A demonstrated superior diagnostic efficacy (AUC: 99.2%) compared to IRX5 (AUC: 87.5%) in distinguishing MTSCC.

Conclusions:

  • VSTM2A is a highly effective diagnostic marker for distinguishing MTSCC from other renal cell carcinomas, even those with overlapping histology.
  • IRX5 also shows promise as a lineage-specific biomarker for MTSCC.
  • The findings suggest that MTSCC shares phenotypic expression patterns with the loop of Henle region of normal nephrons.

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