Objective: To study O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression to access the efficacy of Temozolamide (TMZ) as a part of multimodality treatment.
Background: Aggressive or residual pituitary tumours are associated with substantial morbidity. Treatment options are often limited, and chemotherapy are associated with dismal results. Recent reports have documented the efficacy of TMZ therapy in aggressive pituitary tumors resistant to multimodality therapy. A DNA repair protein, MGMT has been suggested as a biomarker to predict response to TMZ in pituitary tumours.
Design: A total of 28 patients on TMZ therapy on conventional cycles (5/28 days, first cycle-150 mg/m2, subsequent cycles-200 mg/m2, at least three cycles) were analysed. Immunohistochemistry for MGMT could be performed on 20/22 patients who underwent surgery. In addition to MGMT, tissues were also examined for Ki-67 and p53. Relevant positive and negative controls were used for validation. Statistical analysis was done using GraphPad PRISM 7.0. Response was defined according to RECIST criteria for imaging and hormonal values.
Results: There were 14 somatotropinomas (one microadenoma, one primary Gamma Knife Radiosurgery (GKRS)), 12 Prolactinomas (5 not operated, received D2 agonist followed by TMZ as add on), and 2 NFPTs. All patients responded to TMZ therapy (complete3/partial14/stable disease 11). There was significant decrease in prolactin (P=0.004) and IGF-1(P=0.006) in prolactinomas and somatotropinomas respectively. We also observed significant reduction in tumor volume (P<0.0001). Patients who received TMZ post gamma knife surgery responded better (P=0.02) as compared to post intensity modulated radiotherapy. (P=0.16). Apoplexy, Knosp grading, number of surgeries, Ki-67, p53 were not predictive of response to TMZ therapy. A significant proportion of pituitary adenomas demonstrate low MGMT immunoexpression (10/16), however, responders had differential expression of MGMT (P<0.001).
Conclusion: Contradictory to popular belief MGMT expression on IHC can still be used for predictor of response to TMZ therapy in real world setting.