Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Abstract

Background/Objectives: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. Methods: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. Results: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. Conclusions: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.

Loss of MTAP Expression is a Negative Prognostic Marker in Ewing Sarcoma Family of Tumors

“…Similarly, De Oliveira et al (2016), in a recent breast cancer study, found that loss of MTAP expression was associated with more aggressive tumor subtypes [4]. One of the possible explanations for the association with tumor aggressiveness is that in neoplastic cells MTAP inactivation stimulates de novo synthesis of purines, which is related to increased cell proliferation [5]. In contrast, MTAP-deficient neoplastic cells are more sensitive to purine synthesis inhibitor agents, such as methotrexate, azathioprine and 5 -fluorouracil (5 -FU), which indicates that MTAP is a promising therapeutic target [2].…”

“…A manual immunohistochemical assay on the TMA slides was performed for subsequent MTAP evaluation as previous reported [5]. Starfrost R adhesive slides (Kinttel, Braunshweig, Germany) were used for the immunohistochemical study.…”

“…Deficiency of this enzyme has been recently found in different types of neoplasms, mainly due to deletion of the 9p21 locus, and associated with increased tumor aggressiveness [1,[3][4][5]. Su et al (2014), in an immunohistochemistry (IHC) study of 99 lung cancer samples, demonstrated that MTAP was an independent marker of prognosis in patients with non-small-cell lung cancer [3].…”

“…Su et al (2014), in an immunohistochemistry (IHC) study of 99 lung cancer samples, demonstrated that MTAP was an independent marker of prognosis in patients with non-small-cell lung cancer [3]. In the study by Becker et al (2015), the authors suggested that loss of MTAP expression may also be associated with increased malignancy of brain gliomas [5]. Similarly, De Oliveira et al (2016), in a recent breast cancer study, found that loss of MTAP expression was associated with more aggressive tumor subtypes [4].…”

Association of common variants in MTAP with susceptibility and overall survival of osteosarcoma: a two-stage population-based study in Han Chinese

“…It has further been reported that the genetic polymorphisms of MTAP associated with some cancers including OS in Caucasians and ischemic stroke and myocardial infarction in Han Chinese population 24-27. Loss of MTAP expression would exert a tumor-promoting effect, suggesting that MTAP may function as a tumor suppressor gene 28-30. MTAP-deficient cells are reported to be more sensitive than MTAP-positive cells to inhibitors of de novo purine synthesis and to methionine deprivation 31,32.…”