MGMT immunoexpression in aggressive pituitary adenoma and carcinoma

Abstract

Recent case reports have documented the efficacy of temozolomide therapy in some aggressive pituitary adenomas and pituitary carcinomas resistant to multimodality therapy. Evidence suggests that low O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression correlates with response to temozolomide chemotherapy. Herein, we aimed to study MGMT immunoexpression in a spectrum of pituitary tumors, indolent, aggressive and malignant. A literature review of the use of temozolomide in pituitary tumors was also performed. Immunohistochemistry for MGMT was performed on 60 pituitary tumors identified in the Mayo Clinic Tissue Registry and the consultation files of one of us (BWS). The group included 30 pituitary carcinomas (15 ACTH, 10 PRL, 1 FSH/LH, 1 TSH, 1 silent subtype 3 and 2 null cell). Tissue from recurrences was available in 17 cases. In addition, 30 functionally different pituitary adenomas were studied, including 15 invasive and 15 non-invasive adenomas. Overall, 32 cases of pituitary tumors (54%) demonstrated low MGMT immunoexpression. This included 17 of 30 (57%) carcinomas, 9 of 15 (60%) invasive adenomas, and 6 of 15 cases (40%) of non-invasive pituitary adenomas. There was no significant change in MGMT immunoexpression between primary and recurrent tumors. Prolactin-producing carcinomas had the highest proportion of tumors (80%) with low expression. A significant proportion of pituitary adenomas and carcinomas demonstrate low MGMT immunoexpression. In an effort to anticipate the likelihood of a temozolomide response, all cases of aggressive pituitary tumors should be assessed for MGMT expression.

Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas

“…Recently, the upregulation of mitogen-activated protein kinase has also been reported in gangliogliomas [37]. Moreover, when the methylation status of O(6)-methylguanine DNA methyltransferase (MGMT) was examined in pituitary adenomas, the degree of MGMT expression appeared to be related to therapeutic responses to temozolomide [1,24,26]. MGMT protein expression was also implicated as a prognostic factor for patients with low-grade gangliogliomas [11].…”

MGMT promoter methylation and immunoexpression in aggressive pituitary adenomas and carcinomas

“…Patient and tumor characteristics for both the SS3 pituitary adenomas and carcinomas were retrieved from our previously reported studies [33,34]. As previously reported, all tumors had been studied for MGMT immunoexpression [34,35].…”

Pituitary Adenomas – Clinico-Pathological, Immunohistochemical and Ultrastructural Study

“…In all PA types, atypia and mitotic cells are rare. Despite the histologically benign aspect, pituitary adenomas may have an invasive behavior (Chang, 2010;Lau, et al, 2010;Li-Ng, 2008;Melmed, 2010;Scheithauer, 1986;Zada et al, 2011;). This factor is not necessarily indicative of malignancy, because tumor growth is slow and metastases are rare.…”