Disease relevance of PRCC

• Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas [1].
• PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21) [2].
• There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials [3].
• Furthermore, papillary adenomas were more commonly found in kidneys removed for PRCC (25%, 18/71) than in kidneys harboring clear-cell RCC (1.9%, 6/318) [4].
• The predominant expression profiles were as follows: CRCC, CK7-/KIT-/PAX2+ (26/37); PRCC, CK7+/KIT-/PAX2+ (17/20); ChC, CK7+/KIT+/PAX2- (10/11); and oncocytoma, CK7-/KIT+/PAX2+ (19/23) [5].

Psychiatry related information on PRCC

• It is suggested that genetic differences between PRCC and other RCC variants may be exploited in the future for surgical decision making [6].

High impact information on PRCC

• The papillary renal cell carcinoma (RCC)-associated (X;1)(p11;q21) translocation fuses the genes PRCC and TFE3 and leads to cancer by an unknown molecular mechanism [7].
• We here demonstrate that the mitotic checkpoint protein MAD2B interacts with PRCC [7].
• PRCC is ubiquitously expressed in normal adult and fetal tissues and encodes a putative protein of 491 aa with a relatively high content of prolines [1].
• 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 analyses [3].
• Alterations of known genes in PRCC include missense mutations in the MET oncogene (7q31) and rare translocations fusing TFE3 at Xp11.2 with a variety of other loci [8].

Chemical compound and disease context of PRCC

• Germline mutations in the tyrosine-kinase domain of the MET proto-oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal-cell carcinomas (hereditary PRCC, HPRCC) [9].

Biological context of PRCC

• The translocation results in a fusion of the transcription factor TFE3 gene on the X chromosome to a novel gene, designated PRCC, on chromosome 1 [1].
• Previously, we demonstrated that in t(X;1)(p11;q21)-positive renal cell carcinomas (RCCs), the TFE3 gene on the X chromosome is disrupted and fused to the PRCC gene on chromosome 1 [10].
• The results show that only fusion to PRCC enhanced transcriptional activation, indicating that the ability to enhance the level of transcription from endogenous TFE3 promoters is not a consistent feature of TFE3 fusions [11].
• Recently we found that the human papillary renal cell carcinoma-associated protein PRCC interacts with the cell cycle control protein Mad2B, and translocates this protein to the nucleus where it exerts its mitotic checkpoint function [12].
• The molecular genetic correlates of a recently proposed subclassification of papillary renal cell carcinoma (PRCC) that designates tumors as type 1 and type 2 based on histological features have not yet been established [8].

Anatomical context of PRCC

• In our experience, PRCC tend to loco-regional invasion with lymph node spread [13].
• Morphologically, PRCC differs from other forms of RCC in that it is associated with frequent tumor infiltration by macrophages and lymphocytes, and a tendency for central necrosis and cystic change [14].
• PRCC, usually a low-grade neoplasm, may be associated with cystic degeneration, hemorrhage, and presence of abundant hemosiderin-laden macrophages (HLM) [15].
• In untreated plasma, TPRC measured by IRMA was lower than expected, but in amniotic fluid expected values were obtained [16].

Associations of PRCC with chemical compounds

• The translocation is predicted to result in the fusion of the N-terminal region of the PRCC protein, which includes a proline-rich domain, to the entire TFE3 protein [17].
• Whereas ferrous AXCP reacts with NO to form a predominantly five-coordinate heme-nitrosyl complex via a six-coordinate intermediate, RCCP forms an equilibrium mixture of six-coordinate and five-coordinate heme-nitrosyl species in approximately equal proportions [18].
• Evidence that RCCP has a more accessible distal coordination site than in AXCP stems from the fact that ferric RCCP readily forms a heme complex with exogenous imidazole, whereas AXCP does not [18].
• Plasma angiotensin II correlated significantly with APRA, TPRA, TPRC and plasma angiotensin I (PA I), but not with inactive renin, which suggests that inactive renin does not produce angiotensin II in vivo [19].
• During captopril and saralasin significant increases in TPRC and APRC were found and no change in IPRC [20].

Regulatory relationships of PRCC

• RESULTS: PPET-1 was found to be up-regulated in ccRCC tumor specimens and down-regulated in PRCC tumor specimens [21].

Other interactions of PRCC

• Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas [7].
• Although CCRCC and PRCC share most immunomarkers, CK7 and AMACR expression can be helpful in the differential diagnosis of challenging histologic variants of the two [22].
• In addition, E-cadherin aids in the distinction between types 1 and 2 PRCC [22].
• ECE-1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC [21].
• The percent positive staining of MMP-9 at the invasive front of tumor cells was significantly higher in CRCC than in ChRCC, PRCC, or CoRCC [23].

Analytical, diagnostic and therapeutic context of PRCC

• METHODS: Tissue specimens were harvested from both normal and tumor-affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]) [21].
• Using Flow Cytometry, we analysed the DNA ploidy pattern of 37 paraffin-embedded PRCC [14].
• OBJECTIVE: To ascertain if this subgroup of renal neoplasms demonstrates the cytogenetic abnormalities seen typically in PRCC, that is, trisomy 7 and 17 or CRCC, that is, loss of 3p, using microsatellite analysis for loss of heterozygosity (LOH), and fluorescence in situ hybridization (FISH) for trisomies [24].

References