Cytogenetic and Molecular Tumor Profiling for Type 1 and Type 2 Papillary Renal Cell Carcinoma

Abstract

Purpose: The goal of this study was to evaluate immunohistochemical and cytogenetic features and their prognostic value in papillary renal cell carcinoma (PRCC) subtypes. Experimental Design: 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 1and 107 (68%) type 2 PRCC. Type 2 patients had worse Eastern Cooperative Oncology Group performance status, higherTstages, 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 1more 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.

Histopathologic subtype-specific genomic profiles of renal cell carcinomas identified by high-resolution whole-genome single nucleotide polymorphism array analysis

“…In a study by Klatte et al (15) a cytogenetic analysis was performed to distinguish between the tumor profiles of type I and type II PRCCs. The authors found that loss of chromosome 1p and 3p, and gain of 5q were exclusively observed in type II PRCC, whereas trisomy 17 was more frequent in type I (15). Analysis of the genetic profiles of the PRCC cases in the present study, which comprised six cases of type II and one case of type I, were compatible with this previous report, and the single case of type I PCRR showing trisomy 17 (Table I).…”

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

“…Recently, among patients with clear cell RCC, deletions of 3p were associated with a better prognosis (p ϭ .03) than with loss of 4p, 9p, and 14q, which were associated with a significantly poorer prognosis [63]. In papillary type 1 and type 2 tumors, poorer survival was noted with loss of 9p and 3p, whereas trisomy 17 was associated with a more favorable prognosis [64].…”

MET Is a Potential Target across All Papillary Renal Cell Carcinomas: Result from a Large Molecular Study of pRCC with CGH Array and Matching Gene Expression Array

“…The papillary cores often contain edema fluid, foamy macrophages, and psammoma bodies. Several clinical reports identified type I tumors as being more frequently multiple, bilateral, indolent, low-grade pRCC, whereas type II were associated with higher grade and poor prognosis tumors related to metastatic spread (4)(5)(6)(7).…”