Expression of the mismatch repair protein hMSH2 in carcinoma in situ and invasive cancer of the breast.
BACKGROUND
Dysregulations in the mechanism of DNA-repair are contributed to tumorgenesis and tumorprogression in human cancer. The mismatch repair gene hMSH2 encodes a protein, which recognizes and binds to mismatch-sequences of the DNA.


METHODS
Using immunohistochemical techniques hMSH2 expression was analyzed in invasive cancer (n = 85) and in situ carcinoma (n = 34) of the breast.


RESULTS
The percentage of hMSH2 positive cases was significantly (p = 0.0001) decreased in invasive cancer as compared to in situ carcinomas. There was an association of hMSH2 expression with parameters of unfavorable prognosis, such as lymph node involvement (p = 0.03), higher degree of malignancy (p = 0.05) and higher proliferative activity (p = 0.05).


CONCLUSIONS
During development from in situ to invasive cancer of the breast, hMSH2 expression seems to be downregulated. However, in invasive cancer, hMSH2 expression seems to be associated with tumor progression. This could be explained by the fact that enhanced proliferation of tumor cells results in increased mistakes within DNA replication procedures.
Bock
N
N
Department of Pathology, University of Göttingen, Germany.
Meden
H
H
Regenbrecht
M
M
Jünemann
B
B
Wangerin
J
J
Marx
D
D
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism; D034961:Antigens, Nuclear; D020137:Base Pair Mismatch; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism*; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051718:MutS Homolog 2 Protein; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein