Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes.
OBJECTIVE
To compare gene expression profiles of chromophobe renal cell carcinoma (RCC) and benign oncocytoma, aiming at identifying differentially expressed genes.


METHODS
Nine cases each of chromophobe RCC and oncocytoma were analyzed by oligonucleotide microarray. Candidate genes that showed consistent differential expression were validated by reverse transcription-PCR using 25 fresh-frozen and 15 formalin-fixed, paraffin-embedded tumor samples. Immunohistochemical analysis was also done for two selected gene products, claudin 8 and MAL2.


RESULTS
Unsupervised hierarchical clustering separated the chromophobe RCC and oncocytoma into two distinct groups. By a combination of data analysis approaches, we identified 11 candidate genes showing consistent differential expression between chromophobe RCC and oncocytoma. Five of these genes, AP1M2, MAL2, PROM2, PRSS8, and FLJ20171, were shown to effectively separate these two tumor groups by quantitative reverse transcription-PCR using fresh tissue samples, with similar trends seen on formalin-fixed tissues. Immunohistochemical analysis revealed selective expression of MAL2 and claudin 8 in distal renal tubules, with MAL2 antibody showing differential expression between chromophobe RCC and oncocytoma. Functional analyses suggest that genes encoding tight junction proteins and vesicular membrane trafficking proteins, normally expressed in distal nephrons, are retained in chromophobe RCC and lost or consistently down-regulated in oncocytoma, indicating that these two tumor types, believed to be both derived from distal tubules, are likely distinctive in their histogenesis.


CONCLUSIONS
We showed that chromophobe RCC and oncocytoma are distinguishable by mRNA expression profiles and a panel of gene products potentially useful as diagnostic markers were identified.
Rohan
Stephen
S
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
Tu
Jiangling J
JJ
Kao
Jean
J
Mukherjee
Piali
P
Campagne
Fabien
F
Zhou
Xi K
XK
Hyjek
Elizabeth
E
Alonso
Miguel A
MA
Chen
Yao-Tseng
YT
D033961:Adaptor Protein Complex 1 / Q000235:genetics; D033983:Adaptor Protein Complex mu Subunits / Q000235:genetics; D018249:Adenoma, Oxyphilic / Q000235:genetics* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011510:Proteolipids / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012697:Serine Endopeptidases / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D022161:Transport Vesicles / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D000099271:Prostasin
D033961:Adaptor Protein Complex 1; D033983:Adaptor Protein Complex mu Subunits; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012697:Serine Endopeptidases; D033921:Vesicular Transport Proteins; D000099271:Prostasin; C499064:AP1M2 protein, human; C539364:ESRP1 protein, human; C438606:MAL2 protein, human; C473222:PROM2 protein, human