Immunohistochemical analysis of DNA mismatch-repair enzyme hMSH-2 and Ki-67 in breast carcinomas.
BACKGROUND
The human Mut-S-Homologon-2 (hMSH-2) gene product is a member of a highly conserved family of proteins involved in postrepiclation mismatch repair.


METHODS
We have analyzed hMSH-2 expression in normal breast tissue (n = 10) and breast carcinomas (n = 30). hMSH-2 protein was investigated immunohistochemically on frozen sections using a specific mouse monoclonal antibody (clone FE11). hMSH-2 labelling pattern was compared with the staining pattern of the proliferation marker Ki-67. A hMSH-2-immunoreactivity score (hMSH-2-IRS) for the semiquantitative analysis of hMSH-2 expression is presented.


RESULTS
In normal breast tissue, we only found weak nuclear immunoreactivity for hMSH-2 in 70%, while the remaining 30% were hMSH-2 negative (mean hMSH-2- IRS: 1.00; SD: +/- 0.82). All breast carcinomas analyzed revealed moderate to strong nuclear immunoreactivity (mean hMSH-2-IRS: 7.67; SD: +/- 3.55). hMSH-2 staining was heterogeneous, with visual differences between individual tumour cells. Expression of hMSH-2 protein was consistently and strongly upregulated in tumour cells of breast carcinomas as compared to normal breast tissue. No visual correlation in comparing the labelling patterns for hMSH-2 with the labeliing patterns for Ki-67 (mean percentage of Ki-67 positive tumour cells: 24.33%; SD: +/- 15.35) was observed in breast carcinomas.


CONCLUSIONS
Our findings indicate that (a) hMSH-2 is expressed in normal human breast tissue; (b) expression of hMSH-2 may be of importance for the genetic stability of breast carcinomas in vivo.
Friedrich
M
M
Department of Obstetrics and Gynecology, University of Saarland, Homburg/Saar, Germany.
Meyberg
R
R
Villena-Heinsen
C
C
Woll-Hermann
A
A
Reitnauer
K
K
Schmidt
W
W
Tilgen
W
W
Reichrath
J
J
D020137:Base Pair Mismatch; D001940:Breast / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D051718:MutS Homolog 2 Protein; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein