Cytogenetic and molecular tumor profiling for type 1 and type 2 papillary renal cell carcinoma.
OBJECTIVE
The goal of this study was to evaluate immunohistochemical and cytogenetic features and their prognostic value in papillary renal cell carcinoma (PRCC) subtypes.


METHODS
One hundred fifty-eight cases of PRCC were identified and reclassified by subtype. Tumoral expression of 29 molecular markers was determined by immunohistochemistry. Cytogenetic analyses were done on a prospective series of 65 patients. Associations with clinicopathologic information and disease-specific survival were assessed.


RESULTS
Fifty-one patients (32%) had type 1 and 107 (68%) type 2 PRCC. Type 2 patients had worse Eastern Cooperative Oncology Group performance status, higher T stages, nodal and distant metastases, higher grades, and a higher frequency of necrosis, collecting system invasion and sarcomatoid features. Type 2 showed greater expression of vascular endothelial growth factor (VEGF)-R2 in the tumor epithelium, and of VEGF-R3 in both tumor epithelium and endothelium. Loss of chromosome 1p, loss of 3p, and gain of 5q were exclusively observed in type 2, whereas type 1 more frequently had trisomy 17. Type 2 PRCC was associated with worse survival than type 1, but type was not retained as an independent prognostic factor. Lower PTEN, lower EpCAM, lower gelsolin, higher CAIX, and higher VEGF-R2 and VEGF-R3 expression, loss of 1p, 3p, or 9p, and absence trisomy 17 were all associated with poorer prognosis.


CONCLUSIONS
Type 2 PRCC is associated with more aggressive clinicopathologic features and worse outcome. Molecular and chromosomal alterations can distinguish between PRCC subtypes and influence their prognosis. The effect of 3p loss on survival in PRCC is opposite to the relationship seen in clear cell RCC.
Klatte
Tobias
T
Department of Urology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1738, USA.
Pantuck
Allan J
AJ
Said
Jonathan W
JW
Seligson
David B
DB
Rao
Nagesh P
NP
LaRochelle
Jeffrey C
JC
Shuch
Brian
B
Zisman
Amnon
A
Kabbinavar
Fairooz F
FF
Belldegrun
Arie S
AS
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002869:Chromosome Aberrations; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate