Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements.
ArganiP, LadanyiM.Distinctive neoplasms characterised by specific chromosomal translocations comprise a significant proportion of paediatric renal cell carcinomas. Pathology2003;35:492–498.
2.
ArganiP, AntonescuCR, IlleiPB, Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol2001;159:179–192.
3.
JoyamaS, UedaT, ShimizuK, Chromosome rearrangement at 17q25 and Xp11.2 in alveolar soft-part sarcoma: a case report and review of the literature. Cancer1999;86:1246–1250.
4.
LadanyiM, LuiMY, AntonescuCR, The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene2001;20:48–57.
5.
SaitoT, OdaY, KawaguchiK, Possible association between tumor-suppressor gene mutations and hMSH2/hMLH1 inactivation in alveolar soft part sarcoma. Hum Pathol2003;34:841–849.
6.
TomlinsonGE, NisenPD, TimmonsCF, Cytogenetics of a renal cell carcinoma in a 17-month-old child. Evidence for Xp11.2 as a recurring breakpoint. Cancer Genet Cytogenet 1991;57:11–17.
7.
TonkV, WilsonKS, TimmonsCF, Renal cell carcinoma with translocation (X;1). Further evidence for a cytogenetically defined subtype. Cancer Genet Cytogenet1995;81:72–75.
8.
HemesathTJ, SteingrimssonE, McGillG, Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev1994;8:2770–2780.
9.
SteingrimssonE, TessarolloL, PathakB, Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development. Proc Natl Acad Sci USA2002;99:4477–4482.
10.
TakemotoCM, YoonYJ, FisherDE. The identification and functional characterization of a novel mast cell isoform of the microphthalmia-associated transcription factor. J Biol Chem2002;277:30244–30252.
11.
VerasteguiC, BertolottoC, BilleK, TFE3, a transcription factor homologous to microphthalmia, is a potential transcriptional activator of tyrosinase and TyrpI genes. Mol Endocrinol2000;4:449–456.
12.
de JongB, MolenaarIM, LeeuwJA, Cytogenetics of a renal adenocarcinoma in a 2-year-old child. Cancer Genet Cytogenet1986;21:165–169.
13.
SidharSK, ClarkJ, GillS, The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum Mol Genet1996;5:1333–1338.
14.
WetermanMA, WilbrinkM, Geurts van KesselA.Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas. Proc Natl Acad Sci USA1996;93:15294–15298.
15.
HeimannP, El HousniH, OgurG, Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-bearing papillary renal cell carcinomas. Cancer Res2001;61:4130–4135.
16.
KovacsG, SzucsS, De RieseW, Specific chromosome aberration in human renal cell carcinoma. Int J Cancer1987;40:171–178.
17.
ClarkJ, LuYJ, SidharSK, Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma. Oncogene1997;15:2233–2239.
18.
ArganiP, LuiMY, CouturierJ, A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). Oncogene2003;22:5374–5378.
19.
DijkhuizenT, van den BergE, WilbrinkM, Distinct Xp11.2 breakpoints in two renal cell carcinomas exhibiting X;autosome translocations. Genes Chromosomes Cancer1995;14:43–50.
20.
DijkhuizenT, van den BergE, StörkelS, Two cases of renal cell carcinoma, clear cell type, revealing a t(6;11)(p21;q13) [abstract]. Cancer Genet Cytogenet1996;91:141.
21.
DavisIJ, HsiBL, ArroyoJD, Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11) (p21;q13) chromosome translocation. Proc Natl Acad Sci USA2003;100:6051–6056.
22.
Dal CinP, van GoolS, BrockP, Renal cell carinoma in a child. Cancer Genet Cytogenet1991;57:137–138.
23.
ArganiP, LalP, HutchinsonB, Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol2003;27:750–761.
24.
SkalskyYM, AjuhPM, ParkerC, PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors. Oncogene2001;20:178–187.
25.
WetermanMA, van GroningenJJ, TertoolenL, Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas. Proc Natl Acad Sci USA2001;98:13808–13813.
26.
MathurM, DasS, SamuelsHH. PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration. Oncogene2003;22:5031–5044.
27.
BronnerCE, BakerSM, MorrisonPT, Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature1994;368:258–261.
28.
FishelR, LescoeMK, RaoMR, The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell1993;75:1027–1038.
29.
FishelR, KolodnerRD. Identification of mismatch repair genes and their role in the development of cancer. Curr Opin Genet Dev1995;5:382–395.
30.
LoebLA. Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res1994;54:5059–5063.
31.
ThibodeauSN, FrenchAJ, RochePC, Altered expression of hMSH2 and hMLH1 in tumors with micro-satellite instability and genetic alterations in mismatch repair genes. Cancer Res1996;56:4836–4840.
32.
ShiaJ, KlimstraDS, NafaK, Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol2005;29:96–104.
33.
RenkonenE, ZhangY, LohiH, Altered expression of MLH1, MSH2, and MSH6 in predisposition to hereditary non-polyposis colorectal cancer. J Clin Oncol2003;21:3629–3637.
34.
MullerW, BurgartLJ, Krause-PaulusR, The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)—results of an international collaborative study. Fam Cancer2001;1:87–92.
