I have read with great interest the paper entitled, “Treatment of Pituitary Neoplasms With Temozolomide: A Review” by Syro et al.1 The authors considered a series of aggressive pituitary tumors in order to evaluate the efficaciousness of temozolomide and to correlate low-level MGMT immunoexpression with a favorable response. Their study represents an accurate review of this topic. However, in my opinion, an aspect of their article is challenging.
The role of temozolomide in the treatment of aggressive pituitary adenomas and carcinomas continues to assume a more prominent significance in literature concerning this therapeutic approach. However, the significance of MGMT immunoexpression in predicting the response to therapy appears more ambiguous. The authors1 stated a finding that low-level MGMT immunoexpression is correlated with a favorable response. However, this statement doesn't seem reliable. In the same article,1 the authors also stated that all 6 carcinomas responded to therapy, but in a contemporaneous study,2 the same authors observed that only 57% of carcinomas demonstrated low MGMT immunoexpression. I wonder about the usefulness of an antibody that doesn't recognize nearly 1 out of 2 cases! This is a crucial feature because the DNA repair enzyme, MGMT, antagonizes the genotoxic effects of temozolomide, and MGMT promoter methylation is the key mechanism of MGMT gene silencing, predictive of a favorable response.
Already several articles3 have revealed some reservations about the association of MGMT immunoexpression with treatment response. In addition, it is well-known that in malignant gliomas, immunohistochemical determination of MGMT protein expression has not proven reliable for diagnostic purposes4 and that the assessment of the MGMT promoter methylation status is usually assessed by methylation-specific polymerase chain reaction. Given the behavioral unpredictability of pituitary tumors, the identification, to date, of so-called atypical adenomas and even more so of pituitary carcinomas (recognizable only after that tumor metastasized) remains controversial.5 Patients, surgeons, and clinicians are still waiting for tools that permit an early detection of aggressive pituitary tumors. Nevertheless, a semiquantitative immunohistochemical assay of MGMT subject to interobserver variability and performed in tumors that, although aggressive, are frequently morphologically indistinguishable from a typical pituitary adenoma could add further doubt. Probably a more correct identification of MGMT status may be achieved with methylation-specific polymerase-chain reaction. In conclusion, further investigations should be performed in pituitary tumors to correlate response to temozolomide with MGMT promoter methylation status.