Analysis of MLH1 and MSH2 Expression in Ovarian Cancer before and after Platinum Drug-based Chemotherapy
Preclinical studies have demonstrated a relationship between DNA mismatch repair (MMR) status and sensitivity to cisplatin and carboplatin. MMR-deficient cells are resistant to both drugs, and selection for cisplatin resistance in vitro is sometimes accompanied by loss of MMR protein expression. We...
Gespeichert in:
Veröffentlicht in: | Clinical cancer research 2000-04, Vol.6 (4), p.1415-1421 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Preclinical
studies have demonstrated a relationship between DNA mismatch repair
(MMR) status and sensitivity to cisplatin and carboplatin.
MMR-deficient cells are resistant to both drugs, and selection for
cisplatin resistance in vitro is sometimes accompanied
by loss of MMR protein expression. We used immunohistochemical staining
techniques to investigate hMLH1 and hMSH2 expression in paired ovarian
tumor sections from 54 ovarian cancer patients before and after
platinum-based therapy. We sought associations between hMLH1 and hMSH2
protein expression and clinical parameters known to be of prognostic
significance as well as response to treatment and overall survival.
hMLH1 and hMSH2 staining decreased significantly after platinum-based
therapy. The percent of malignant cells that stained positive
correlated with the intensity of nuclear staining for both proteins;
staining for hMLH1 correlated well with staining for hMSH2.
Unexpectedly, expression of nuclear hMLH1 correlated negatively with
response to treatment. Expression of nuclear hMLH1 and hMSH2 was
positively correlated with pretreatment CA125 level, and expression of
nuclear hMSH2 was positively correlated with change in CA125 level
after treatment. Tumor stage was associated with expression of nuclear
hMSH2, and tumor histological subtype was associated with both hMLH1
and hMSH2 staining. No association was found between expression of
either protein and overall survival. These results indicate that the
tumor is biologically altered after chemotherapy consistent with
treatment-induced selection for cells expressing lower hMLH1 and hMSH2
levels. However, immunohistochemical staining for either hMLH1 or hMSH2
was not highly predictive of drug sensitivity as measured by response
or survival. |
---|---|
ISSN: | 1078-0432 1557-3265 |