Expression profiling of renal epithelial neoplasms

A method for tumor classification and discovery of diagnostic molecular markers

Andrew N. Young, Mahul Amin, Carlos S. Moreno, So Dug Lim, Cynthia Cohen, John A. Petros, Fray F. Marshall, Andrew S. Neish

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes - vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3 - was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.

Original languageEnglish (US)
Pages (from-to)1639-1651
Number of pages13
JournalAmerican Journal of Pathology
Volume158
Issue number5
DOIs
StatePublished - Jan 1 2001

Fingerprint

Glandular and Epithelial Neoplasms
Molecular Pathology
Kidney Neoplasms
Oxyphilic Adenoma
Renal Cell Carcinoma
Nephrons
Vimentin
Parvalbumins
Neoplasms
Major Histocompatibility Complex
Genes
Galectin 3
Gene Expression
MHC Class II Genes
Oxidative Phosphorylation
Oligonucleotide Array Sequence Analysis
Transcriptome
Cluster Analysis
Mitochondria
Epithelium

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Expression profiling of renal epithelial neoplasms : A method for tumor classification and discovery of diagnostic molecular markers. / Young, Andrew N.; Amin, Mahul; Moreno, Carlos S.; Lim, So Dug; Cohen, Cynthia; Petros, John A.; Marshall, Fray F.; Neish, Andrew S.

In: American Journal of Pathology, Vol. 158, No. 5, 01.01.2001, p. 1639-1651.

Research output: Contribution to journalArticle

Young, Andrew N. ; Amin, Mahul ; Moreno, Carlos S. ; Lim, So Dug ; Cohen, Cynthia ; Petros, John A. ; Marshall, Fray F. ; Neish, Andrew S. / Expression profiling of renal epithelial neoplasms : A method for tumor classification and discovery of diagnostic molecular markers. In: American Journal of Pathology. 2001 ; Vol. 158, No. 5. pp. 1639-1651.
@article{08e98f6e113e4f5da77dbbc500c1ce53,
title = "Expression profiling of renal epithelial neoplasms: A method for tumor classification and discovery of diagnostic molecular markers",
abstract = "The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes - vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3 - was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.",
author = "Young, {Andrew N.} and Mahul Amin and Moreno, {Carlos S.} and Lim, {So Dug} and Cynthia Cohen and Petros, {John A.} and Marshall, {Fray F.} and Neish, {Andrew S.}",
year = "2001",
month = "1",
day = "1",
doi = "10.1016/S0002-9440(10)64120-X",
language = "English (US)",
volume = "158",
pages = "1639--1651",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Expression profiling of renal epithelial neoplasms

T2 - A method for tumor classification and discovery of diagnostic molecular markers

AU - Young, Andrew N.

AU - Amin, Mahul

AU - Moreno, Carlos S.

AU - Lim, So Dug

AU - Cohen, Cynthia

AU - Petros, John A.

AU - Marshall, Fray F.

AU - Neish, Andrew S.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes - vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3 - was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.

AB - The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes - vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3 - was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.

UR - http://www.scopus.com/inward/record.url?scp=0035012170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035012170&partnerID=8YFLogxK

U2 - 10.1016/S0002-9440(10)64120-X

DO - 10.1016/S0002-9440(10)64120-X

M3 - Article

VL - 158

SP - 1639

EP - 1651

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -