MGMT and PTEN as potential prognostic markers in breast cancer.
OBJECTIVE
To evaluate the prognostic importance of MGMT and PTEN concerning their correlation with other prognostic factors evaluated by immunohistochemistry (IHC) and the molecular phenotype of breast cancers.


METHODS
IHC for estrogen and progesterone receptors, HER2, Ki67, p53, p63, e-cadherin, EGFR, CK5, CK14, MGMT and PTEN was performed on 200 breast tumors. Basal-like and luminal breast carcinomas were defined by the IHC evaluation of these markers. Fluorescent in situ hybridization (FISH) was performed for PTEN and HER2 analysis using the Vysis PTEN and HER2 DNA probe kits (Abbott™). RT-PCR was performed to evaluate gene expressions of MGMT and PTEN in frozen tissue of 59/200 cases.


RESULTS
147/200 cases were triple-negative (73.5%), 47/147 were basal-like carcinomas (31.9%). 53 cases (26.5%) were luminal-like type A or B. 56 (93.3%) and 46 samples (76.6%) expressed lower levels of MGMT and PTEN mRNA, respectively, compared with normal breast (p<0.001). There was a positive correlation between the IHC results and the RT-PCR values for MGMT and PTEN. Tumors with homozygotic deletion of PTEN expressed little or no mRNA or protein. Positive p53, high Ki67, and basal-like tumors expressed significant lower MGMT and PTEN.


CONCLUSIONS
We hypothesize that MGMT and PTEN expressions have prognostic significance in breast cancer. Also, based on their predictive value of response to therapy, evaluating MGMT and PTEN and learning to interpret their patterns of immunoexpression will undoubtedly lead to a greater understanding of breast cancer and its treatment.
Dept Anatomic Pathology/Cancer Hospital A C Camargo, Rua Antônio Prudente, 109, 1st floor, Liberdade, São Paulo, SP, Brazil.
Julio Cirullo
JC
Neto
Mariana Mari
MM
Ikoma
Katia Cândido
KC
Carvalho
José
J
Vassallo
Marina
M
De Brot
Helenice
H
Gobbi
Fernando Augusto
FA
Soares
Rafael Malagoli
RM
Rocha
D000906:Antibodies; D014408:Biomarkers, Tumor / Q000235:genetics*; D001938:Brazil; D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000906:Antibodies; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D045643:DNA Repair Enzymes