Table 3

Biomarkers used to differentiate chromophobe renal cell carcinoma (RCC) (chRCC) from oncocytoma (RO)

MethodNumber of patientsSignificance of success as biomarkerReference
BCA2158 patients (104 ccRCC, 8 chRCC, 2 pRCC, 38 RO, 6 oncocytic neoplasmsAll RO and oncocytic neoplasms, which favour RO, were positive for BCA2 while all RCC were negative, including chRCC.50
C-kit (encodes the membrane-bound tyrosine kinase KIT)mRNA levels, 17 chRCC, 20 RO from cDNA microarrays
IHC analysis, 226 renal tumours in TMAs (40 chRCC, 41 RO, 40 ccRCC, 29 renal angio-myolipoma, 21 pRCC).
Significant increment of c-kit mRNA and overexpression of KIT protein by IHC in chRCC and RO, hence low potential for differentiating between the two types. However, there was potential for differentiating chRCC/RO from the other renal cell tumours (ccRCC and pRCC).62
EMA86 retrospective nephrectomy specimens (15 ccRCCs, 15 pRCCs, 15 chRCCs, 10 ROs, 6 cdc)EMA was positive in chRCC (75–100%), ccRCC (50–77%) and oncocytomas (51–86%), showing no major promise as a marker. (Comparison made with
3 tubulocystic carcinoma, 3 renal medullary carcinoma, 3 mucinous tubular and spindle cell carcinoma, 4 metanephric adenoma, 12 invasive high-grade urothelial carcinoma)
76 cases (30 ccRCC, 16 pRCC, 21 chRCC, 8 RO, 1 cdc)EMA was positive in 100% of ChRCCs, 100% of ROs and 75% of ccRCC. So, we concluded that EMA is not a good marker for the differentiation of renal tumours.45
Carbonic anhydrase IX (CA IX)TMAs, 20 cases of each ccRCC, chRCC, pRCC and ROCA IX was highly sensitive for ccRCCs (90% positivity) and was negative in all other renal epithelial tumours except for 1 chRCC.48
Galectin-3TMAs, 20 cases of each ccRCC, chRCC, pRCC and ROGalectin-3 found mostly in renal tumours with oncocytic features, including RO (100%) and chRCCs (89%). May hold small promise to distinguish these from other RCC.48
Glutatione S-transferase alpha (GST-α)22 chRCC, 17 RO, 45 ccRCCGST-α exclusively observed in ccRCCs.47
KIT (CD117)256 ccRCC, 29 chRCC, 25 pRCC, 6cdc, 6 unclassified RCC, 7 RO, 20 UC, 7 NB, 2 AM83% chRCCs and 71% RO had membranous immunoreactivity for KIT, while none of the other RCC or the angiomyolipomas expressed. Cannot be used to differentiate chRCC and RO.63
11 chRCCs, 12 RO, 6 ccRCCKIT was a very sensitive marker for both chRCC and RO, but not useful to differentiate between the two. KIT with RCCma may be useful when trying to differentiate ccRCCs from chRCCs or ROs.58
22 chRCC, RO & ccRCCCD117, strongly expressed in chRCC (82%) and RO (100%), whereas none of the ccRCCs were immunoreactive.47
CD1510 ccRCC, pRCC, chRCC and ROCD15 was able to distinguish between chRCCs and RO. 7/10 RO (70%) stained positive for CD15 and none of the chRCC stained for CD15.64
MAGE-A3/4 cancer testis antigen/CTA35 patients (17 RO, 18 chRCC)88% RO stained positively for MAGE-A3/4; 39% chRCC stained positively51
RON proto-oncogene, encoding a receptor tyrosine kinase,TMAs (55 RO, 52 chRCCs).15 & 5 conventional sections of RO & chRCC were also analysed69 of 70 RO and 55 of 57 chRCC had strong, diffuse cytoplasmic stain.65
11 chRCC, 12 RO, 6 ccRCCs11/11 chRCCs, 12/12 RO, but only 3/6 of ccRCC.58
NY-ESO-1 CTA35 patients (17 RO, 18 chRCC)15/17 RO stained positive, and 6/18 chRCC were positive.51
Interphase fluorescence in situ hybridisation (FISH)11 chRCC, 12 RO, compared with conventional metaphase cytogenetics by karyotyping.RO often show normal DNA content by interphase and metaphase analyses. The loss of 2 or more of chromosomes 1, 2, 6, 10, and 17 favours the diagnosis of chRCC over RO. FISH analysis is shown to be a useful tool that helps identify differences between these 2 tumour types.66
Endogenous avidin-binding activity (EABA)Renal TMAs (30 RO, 18 chRCC, 64 ccRCC, 50 pRCC, 31 benign renal tissues)97% RO, 26% ccRCC, 35% pRCC with granular/eosinophilic (GE) features and 6% of chRCCs positive for EABA. RCC without GE features were negative. EABA is an excellent marker for RO, and so useful in differentiating RO from chRCC.60
PAX8 and MUC-1TMAs of 36 chRCC, 20 ROExpression of PAX8 more frequent in RO than in chRCC (55% vs 25%).
MUC1 expressed more diffusely and frequently in chRCC than RO (94% vs 55%).
  • AM, angiomyolipomas; BCA2, a RING H2 finger protein of RING E3 ligases; ccRCC, clear cell renal cell carcinoma; cdRCC, collecting duct renal cell carcinoma; chRCC, chromophobe renal cell carcinoma; NB, nephroblastomas; pRCC, papillary renal cell carcinoma; RO, renal oncocytoma; UC, urothelial carcinomas.