Inverse correlation between the expression of O6-methylguanine-DNA methyl transferase (MGMT) and p53 in breast cancer.
BACKGROUND
Expression of O(6)-methylguanine-DNA methyl transferase (MGMT), a DNA repair protein, has been associated with tumor resistance to alkylating agents such as cyclophosphamide. Promoter hypermethylation of MGMT is a strong predictor of survival, and expression of mutant p53 protein may be associated with downregulated MGMT expression in brain tumors. In order to clarify further the correlation between MGMT and p53 expression, we investigated the expression levels of both MGMT and p53 in breast cancer.


METHODS
MGMT and p53 expression was examined in tissues from 48 consecutive cases of primary breast cancer patients using immunohistochemical staining with antibodies specific for MGMT and p53. The prognosis for survival was analyzed based on MGMT and p53 immunoreactivity and clinicopathological characteristics.


RESULTS
Expression of either MGMT or p53 was classified as negative or positive based on immunohistochemical staining. The expression of MGMT showed a significant inverse correlation with three clinicopathological characteristics, the status of the estrogen receptor, local recurrence and distant metastasis. There was a significant correlation between the expression level of p53 and the lymphatic involvement, estrogen receptor status and distant metastasis. MGMT and p53 were correlated with distant metastasis and local recurrence, but Kaplan-Meier curves did not show a significant difference. MGMT immuno-negative specimens showed a significantly higher expression of p53 (P = 0.026, chi(2) test).


CONCLUSIONS
p53 may be associated with the regulation of MGMT expression in breast cancers.
Osanai
Takayuki
T
Surgical Oncology, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan. t-osanai.srg2@tmd.ac.jp
Takagi
Yoko
Y
Toriya
Yoichi
Y
Nakagawa
Tsuyoshi
T
Aruga
Tomoyuki
T
Iida
Satoru
S
Uetake
Hiroyuki
H
Sugihara
Kenichi
K
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D019853:O(6)-Methylguanine-DNA Methyltransferase