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

4503 Background: Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphological classification of PRCC into Type 1 and Type 2 tumors has been recently proposed, but its biological relevance remains uncertain. Methods: We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analysis. Comparative genomic microarray analysis (CGMA) was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples, with 15 independent tumors. Results: We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histological subtypes: Type 1, low-grade Type 2 and mixed Type 1/low-grade Type 2 tumors. The second class, with poor survival, corresponded to high-grade Type 2 tumors (n = 11). Dysregulation of G1/S and G2/M checkpoint genes were found in Class 1 and Class 2 tumors respectively, alongside characteristic chromosomal aberrations. We identified a 7-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in Class 1 tumors, and of topoisomerase IIα in Class 2 tumors. Conclusions: We report two molecular subclasses of PRCC, which are biologically and clinically distinct, which may be readily distinguished in a clinical setting. This may also have therapeutic implications. No significant financial relationships to disclose.

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MP36-01 CAN MULTIPHASE CT SCAN DISTINGUISH BETWEEN TYPE 1 AND TYPE 2 PAPILLARY RENAL CELL CARCINOMA? A RETROSPECTIVE ANALYSIS

The Journal of Urology ◽

10.1016/j.juro.2014.02.1065 ◽

2014 ◽

Vol 191 (4S) ◽

Author(s):

Michelle McDonald ◽

Hak Lee ◽

Vipulkumar Dadhania ◽

Song Wang ◽

Ryan Kopp ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Ct Scan ◽

Cell Carcinoma ◽

Retrospective Analysis ◽

Renal Cell ◽

Papillary Renal Cell Carcinoma ◽

Multiphase Ct

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Presence and percentage of type 2 papillary RCC in mixed (type 1 and type 2) papillary renal cell carcinoma does not portend worse prognosis in patients treated by partial/radical nephrectomy in non-metastatic disease.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e16126 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e16126-e16126

Author(s):

Andrew Leone ◽

Gregory Diorio ◽

Joseph Brito ◽

Kamran Zargar ◽

Gyan Pareek ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Radical Nephrectomy ◽

Mixed Type ◽

Papillary Renal Cell Carcinoma ◽

Papillary Rcc ◽

Worse Prognosis

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Unique Patterns of Allelic Imbalance Distinguish Type 1 from Type 2 Sporadic Papillary Renal Cell Carcinoma

American Journal Of Pathology ◽

10.1016/s0002-9440(10)64260-5 ◽

2002 ◽

Vol 161 (3) ◽

pp. 997-1005 ◽

Cited By ~ 55

Author(s):

Melinda E. Sanders ◽

Rosemarie Mick ◽

John E. Tomaszewski ◽

Frederic G. Barr

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Allelic Imbalance ◽

Papillary Renal Cell Carcinoma

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Survival Analysis of 130 Patients with Papillary Renal Cell Carcinoma: Prognostic Utility of Type 1 and Type 2 Subclassification

Urology ◽

10.1016/j.urology.2006.09.052 ◽

2007 ◽

Vol 69 (2) ◽

pp. 230-235 ◽

Cited By ~ 154

Author(s):

Géraldine Pignot ◽

Caroline Elie ◽

Sophie Conquy ◽

Annick Vieillefond ◽

Thierry Flam ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Survival Analysis ◽

Cell Carcinoma ◽

Renal Cell ◽

Papillary Renal Cell Carcinoma ◽

Prognostic Utility

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Type 1 papillary renal cell carcinoma: differentiation from Type 2 papillary RCC on multiphasic MDCT

Abdominal Radiology ◽

10.1007/s00261-017-1091-x ◽

2017 ◽

Vol 42 (7) ◽

pp. 1911-1918 ◽

Cited By ~ 12

Author(s):

Jonathan R. Young ◽

Heidi Coy ◽

Michael Douek ◽

Pechin Lo ◽

James Sayre ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Papillary Renal Cell Carcinoma ◽

Papillary Rcc

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Functional magnetic resonance imaging for distinguishing type of papillary renal cell carcinoma: a preliminary study

British Journal of Radiology ◽

10.1259/bjr.20201315 ◽

2021 ◽

Vol 94 (1126) ◽

pp. 20201315

Author(s):

Qingqiang Zhu ◽

Jing Ye ◽

Wenrong Zhu ◽

Jingtao Wu ◽

Wenxin Chen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Magnetic Resonance ◽

Cell Carcinoma ◽

Renal Cell ◽

Mean Diffusivity ◽

Papillary Renal Cell Carcinoma ◽

Diffusion Kurtosis Imaging ◽

D Values

Objective: To investigate the feasibility of magnetic resonance diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) for distinguishing Type 1 and 2 of papillary renal cell carcinoma (PRCC). Methods: A total of Type 1 (n = 20) and Type 2 (n = 16) of PRCC were examined by pathology. For DKI and IVIM, mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK), kurtosis anisotropy (KA), radial kurtosis (RK), diffusivity (D), pseudodiffusivity (D*) and perfusion fraction (f) were performed in assessment of type of PRCC. Results: The mean SNRs of IVIM and DKI images at b = 1500 and 2000 s/mm2 were 8.6 ± 0.8 and 7.8 ± 0.6. Statistically significant differences were observed in MD and D values (1.11 ± 0.23 vs 0.73 ± 0.13, 0.91 ± 0.24 vs 0.49 ± 0.13, p < 0.05) between Type 1 and Type 2 of PRCC, while comparable FA, RK, D* and f values were found between Type 1 and Type 2 of PRCC (p > 0.05). Statistically significant differences were observed in MK and KA values (1.23 ± 0.16 vs 1.91 ± 0.26, 1.49 ± 0.19 vs 2.36 ± 0.39, p < 0.05) between Type 1 and Type 2 of PRCC. Areas of MD, MK, KA and D values under ROC curves for differentiating Type 1 and Type 2 of PRCC were 0.836, 0.818, 0.881 and 0.766, respectively. Using MD, MK, KA and D values of 0.93, 1.64, 1.94, 0.68 as the threshold value for differentiating Type 1 from Type 2 of PRCC, the best result obtained had a sensitivity of 85.0%, 80.0%, 90.0%, 85.0%, a specificity 75.0%, 68.7%, 87.5%, 81.2%, and an accuracy of 83.3%, 80.5%, 88.9%, 86.1%, respectively. Conclusion: DKI and IVIM are feasible techniques for distinguishing type of PRCC, given an adequate SNR of IVIM and DKI images. Advances in knowledge: 1. MD and D values are higher for Type 1 of PRCC and lower for Type 2 of PRCC. 2. MK and KA values are higher for Type 2 of PRCC and lower for Type 1 of PRCC. 3. DKI and IVIM can be used as clinical biomarker for PRCC type’s differential diagnosis, given an adequate SNR.

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