O(6)-methylguanine-DNA methyl transferase gene expression and prognosis in breast carcinoma.
O(6)-methylguanine-DNA methyl transferase (MGMT) in human carcinomas has been associated with tumor resistance to alkylating agents. The aims of this study were: i) to correlate tumor MGMT expression and patient and tumor characteristics in malignant breast carcinomas treated with induction chemotherapy including cyclophosphamide (CPM) and ii) to study the predictive and prognostic values of tumor MGMT gene expression. We used RT-PCR to measure the levels of tumor MGMT expression in 107 patients with breast carcinomas prior to neoadjuvant chemotherapy. Sixty patients (56%) received anthracyclines and CPM and 47 (44%) received only anthracyclines. Low levels of MGMT expression correlated with Scarff-Bloom-Richardson grade III (p<0.005), elevated S-phase (p<0.05), negative estrogen receptors (p<0.05), metastatic status (p<0.05) and occurrence of death (p=0.01). MGMT expression was not predictive of treatment response. Unexpectedly, survival was longer when tumor MGMT expression was high (p<0.005). The 4-year survival rate was 76% for high level MGMT patients and only 55% for others. This difference is also significant using the COX model (p<0.05). In breast cancer, tumor MGMT expression was not predictive of response to CPM. A low MGMT expression was significantly related to poor survival.
Cayre
Anne
A
Department of Pathology, Centre Jean Perrin, BP 392, 63011 Clermont-Ferrand Cédex, France. top@cjp.u-clermont1.fr
Penault-Llorca
Frédérique
F
De Latour
Monique
M
Rolhion
Christine
C
Feillel
Viviane
V
Ferrière
Jean-Pierre
JP
Kwiatkowski
Fabrice
F
Finat-Duclos
Françoise
F
Verrelle
Pierre
P
D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004260:DNA Repair; D005260:Female; D015870:Gene Expression; D006801:Humans; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D003520:Cyclophosphamide; D019853:O(6)-Methylguanine-DNA Methyltransferase