Profiling and classification tree applied to renal epithelial tumours.
OBJECTIVE
Selection of the relevant combination from a growing list of candidate immunohistochemical biomarkers constitutes a real challenge. The aim was to establish the minimal subset of antibodies to achieve classification on the basis of 12 antibodies and 309 renal tumours.


RESULTS
Seventy-nine clear cell (CC), 88 papillary (PAP) and 50 chromophobe (CHRO) renal cell carcinomas, and 92 oncocytomas (ONCO) were immunostained for renal cell carcinoma antigen, vimentin, cytokeratin (CK) AE1-AE3, CK7, CD10, epithelial membrane antigen, alpha-methylacyl-CoA racemase (AMACR), c-kit, E-cadherin, Bcl-1, aquaporin 1 and mucin-1 and analysed by tissue microarrays. First, unsupervised hierarchical clustering performed with immunohistochemical profiles identified four main clusters-cluster 1 (CC 67%), 2 (PAP 98%), 3 (CHRO 67%) and 4 (ONCO 100%)-demonstrating the intrinsic classifying potential of immunohistochemistry. A series of classification trees was then automatically generated using Classification And Regression Tree software. The most powerful of these classification trees sequentially used AMACR, CK7 and CD10 (with 86% CC, 87% PAP, 79% CHRO and 78% ONCO correctly classified in a leave-one-out cross-validation test). The classifier was also helpful in 22/30 additional cases with equivocal features.


CONCLUSIONS
The classification tree method using immunohistochemical profiles can be applied successfully to construct a renal tumour classifier.
Allory
Y
Y
AP-HP, Hôpital Henri Mondor, Département de Pathologie, INSERM, IMRB U841, Créteil, France. yves.allory@hmn.aphp.fr
Bazille
C
C
Vieillefond
A
A
Molinié
V
V
Cochand-Priollet
B
B
Cussenot
O
O
Callard
P
P
Sibony
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000145:classification / Q000175:diagnosis / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000175:diagnosis / Q000378:metabolism; D003663:Decision Trees; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053552:Keratin-7 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D040081:Protein Array Analysis; D014746:Vimentin / Q000378:metabolism
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D053552:Keratin-7; D014746:Vimentin; D015260:Neprilysin