Expression of mismatch repair enzymes, hMLH1 and hMSH2 is not associated with microsatellite instability and P53 protein accumulation in basal cell carcinoma.
Microsatellite instability (MSI) constitutes an alternative-to the chromosomal instability-pathway of carcinogenesis for certain tumour types with prognostic and therapeutic significance for the respective patients. MSI is caused by mutations in mismatch repair (MMR) genes, mainly hMLH1, hMSH2, leading to a defective MMR system. The role of MSI in basal cell carcinoma (BCC) has not been clearly delineated yet. p53 gene as a target for ultraviolet radiation-induced mutations may enhance genomic instability in BCC, with loss of its function. Our aim was to investigate the involvement of MSI and expression of hMLH1 and hMSH2 in parallel with P53 protein accumulation in the pathogenesis of BCC and its possible correlation to the clinicopathological features of the patients. The presence of MSI was investigated in 76 BCCs using mononucleotide microsatellite markers, BAT-25, BAT-26 and TGF-beta receptor type II (TGF-beta-RII). Additionally, 3 dinucleotide markers were analysed in 20 cases in which matched normal tissue was available. The expression of hMLH1, hMSH2 and P53 proteins was evaluated by immunohistochemical analysis. Alterations of the BAT-26 marker were observed in one fibroepithelioma of Pincus, one nodular and one multifocal superficial BCC. A keratotic BCC showed an altered BAT-25 locus. Two samples, a multifocal superficial and a nodular BCC, displayed MSI at two markers (BAT-25 and BAT-26; and BAT-25 and TGF-beta-RII, respectively). Three more cases, a metatypical, a multifocal superficial and a signet ring BCC exhibited frameshift mutations in the TGF-beta-RII. No sample showed length alterations at the dinucleotide markers examined. hMLH1 and hMSH2 protein immunohistochemical expression was scored positive in 46 and 49 out of 52 cases respectively. P53 accumulation was observed in 27 out of 56 samples. Correlation of the molecular and immunohistochemical findings with the clinicopathological parameters produced no statistically significant results. No correlation between MSI and hMLH1, hMSH2 or P53 protein expression was determined. MSI appears to play a minor role in the pathogenesis of BCCs being present only in a small subset of such tumours.
Saetta
Angelica A
AA
Department of Pathology, Medical School, The National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 115 27 Athens, Greece. asaetta@med.uoa.gr
Aroni
Kiriaki
K
Stamatelli
Angeliki
A
Lazaris
Andreas C
AC
Patsouris
Efstratios
E
D048868:Adaptor Proteins, Signal Transducing; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein