Loss of hMSH2 expression in primary breast cancer with p53 alterations.
Inactivation of DNA mismatch repair genes (MRG) is a recently described pathway of cancer development and progression resulting in genetic instability. Germline mutations in MRG have been studied predominantly in patients with hereditary non-polyposis colorectal cancer (HNPCC) where it is associated with microsatellite instability (MSI). The expression of MRG in primary breast cancer is still largely unexplored. The hMSH2 MRG encodes a protein that recognizes and binds to mismatch sequences of DNA. We investigated the relation-ship between hMSH2 expression and clinicopathological and biological characteristics, including p53 and p185 expression, in 44 primary invasive breast cancers. hMSH2 was not expressed in 11 cases (25%). Interestingly, p53 (p=0.05), p185 and steroidal receptor expression (p=0.07) were more frequent in tumors without hMSH2 expression. Furthermore, in 30 of 44 cases we analyzed hMSH2 expression in relation to MSI at 9 dinucleotide loci, and found that MRG expression was not significantly related to MSI. The presence of hMSH2 and p53 alterations in the same tumor suggests that the two oncoproteins act through a common mutational pathway, whereas the absence of a correlation between hMSH2 and MSI suggests that oncogenetic mechanisms of progression in primary breast cancer differ from those in HNPCC.
Spagnoletti
Ilaria
I
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università di Napoli 'Federico II', 80131 Napoli, Italy.
Pizzi
Claudia
C
Galietta
Annamaria
A
Di Maio
Massimo
M
Mastranzo
Paolo
P
Daniele
Santa
S
Limite
Gennaro
G
Pettinato
Guido
G
Contegiacomo
Alma
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007120:Immunochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004268:DNA-Binding Proteins; D051718:MutS Homolog 2 Protein; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human