MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy

Kovács, Kálmán; Scheithauer, Bernd W.; Lombardero, Matilde; McLendon, Roger E.; Syro, Luis V.; Uribe, Humberto; Ortíz, León Darío; Penagos, Luis C.

doi:10.1007/s00401-007-0279-5

Cited by 105 publications

(122 citation statements)

References 11 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…16 Their observations were confirmed subsequently by McCormack et al, who assessed MGMT reactivity in a PRL cell carcinoma and an aggressive growth hormone-producing adenoma. 19 In both studies, tumors with low MGMT expression demonstrated a clinical and radiologic response to temozolomide therapy, whereas tumors with high MGMT expression were resistant.…”

Section: Mgmt Immunoexpressionmentioning

confidence: 80%

“…2,20 Thus, determining the level of MGMT immunostaining appears to be useful for predicting the response of aggressive pituitary adenomas and carcinomas to temozolomide. 2 The reports of Kovacs et al 16 and McCormack et al 19 underscored the inverse relation between MGMT immunoexpression and the efficacy of temozolomide therapy, a relation that also has been noted in high-grade gliomas. 51,52 Whereas the standard method of evaluating MGMT status is the identification of promoter methylation, the detection of MGMT expression by immunohistochemistry presents an attractive alternative.…”

Section: Mgmt Immunoexpressionmentioning

confidence: 93%

“…Kovacs et al 16 reported a patient aged 41 years who had an aggressive, silent, subtype 2 corticotrophic adenoma with no morphologic changes after temozolomide treatment. MGMT immunoexpression was positive.…”

Section: Pituitary Adenomasmentioning

confidence: 99%

“…Syro et al 23 and Kovacs et al 15,16 published the only morphologic comparisons of pathology before and after temozolomide treatment. In those studies, operative findings included tumor softening and friability, both of which facilitated resection at reintervention.…”

Section: Morphologic Changesmentioning

confidence: 99%

“…15 Predictably, in the MGMTpositive, silent, subtype 2 corticotrophic adenoma, no such alterations were produced. 16 Radiographic Changes Three patterns of radiographic change have been observed on MRI images from patients who had a good response to temozolomide treatment. These included tumor necrosis and hemorrhage, 15,23 tumor degenerative and cystic changes, 22 and tumor shrinkage.…”

Section: Morphologic Changesmentioning

confidence: 99%

See 4 more Smart Citations

Treatment of pituitary neoplasms with temozolomide

Syro

Ortíz

Scheithauer

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

Temozolomide, an orally administered alkylating agent, is used to treat malignant gliomas. Recent reports also have documented its efficacy in the treatment of pituitary adenomas and carcinomas. Temozolomide methylates DNA and thereby exhibits an antitumor effect. O 6 -methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, removes alkylating adducts induced by temozolomide, counteracting its effects. The authors of this review conducted a Medline database search regarding temozolomide in the treatment of pituitary tumors. Demographic characteristics, tumor types, and therapeutic responses were noted in all patients. Data regarding MGMT immunoexpression, which was documented in some studies, were correlated with information regarding clinical and radiologic responses. To date, there have been 19 reported cases of adenohypophyseal tumors treated with temozolomide, including 13 adenomas and 6 carcinomas. Ten of those 13 adenomas responded favorably, and 2 nonresponsive tumors had highlevel MGMT immunoexpression. All 6 carcinomas responded to therapy, but data regarding MGMT expression were available for only 3 patients, and each had low MGMT expression. In 2 adenomas, morphologic studies were performed both before and after the patients received temozolomide. The responsive tumor had necrosis, hemorrhage, fibrosis, and neuronal differentiation. The nonresponsive tumor had no changes. There have been no reported complications attributable to temozolomide. The current results indicated that temozolomide is efficacious in the treatment of aggressive pituitary adenomas and pituitary carcinomas. Evidence indicated that low-level MGMT immunoexpression is correlated with a favorable response. A significant proportion of pituitary adenomas and carcinomas had low MGMT immunoexpression. Cancer 2011;117:454-62.

show abstract

Section: Mgmt Immunoexpressionmentioning

confidence: 80%

Section: Mgmt Immunoexpressionmentioning

confidence: 93%

Section: Pituitary Adenomasmentioning

confidence: 99%

Section: Morphologic Changesmentioning

confidence: 99%

Section: Morphologic Changesmentioning

confidence: 99%

See 3 more Smart Citations

Treatment of pituitary neoplasms with temozolomide

Syro

Ortíz

Scheithauer

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

Errata

2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

O⁶‐methylguanine DNA methyltransferase immunoexpression in nonfunctioning pituitary adenomas

Widhalm

Wolfsberger

Preusser

et al. 2009

Cancer

View full text Add to dashboard Cite

BACKGROUND: Currently, no effective alternative treatment exists for progressive, regrowing, nonfunctioning pituitary adenomas (NFPA) that are resistant to conventional multimodality therapy. Temozolomide (TMZ) was proposed as a treatment option for pituitary carcinomas and aggressive pituitary adenomas. Recently, it was suggested that the responsiveness of pituitary tumors to TMZ depends on the immunoexpression of O 6methylguanine DNA methyltransferase (MGMT). Therefore, the authors of this report assessed MGMT expression in a series of patients with progressive, regrowing NFPAs to evaluate whether TMZ may serve as alternative treatment option. METHODS: On the basis of postoperative magnetic resonance imaging, 45 patients with NFPAs were allocated to either a group with progressive, regrowing tumors (n ¼ 24) or a tumor-free group (n ¼ 21), which served as a control. MGMT expression was assessed semiquantitatively by immunohistochemistry (low expression was defined as 50% immunostained adenoma cells, and high expression was defined as >50% immunostained adenoma cells) and was compared between the 2 groups. RESULTS: At the time of initial surgery, low MGMT expression was observed in 12 of 24 patients (50%) in the study group with progressive, regrowing NFPAs. In the control group of tumor-free patients, only 5 of 21 patients (24%) exhibited low MGMT expression. A comparable distribution of MGMT expression was observed in the specimens from repeat surgeries. A shorter interval to second surgery was observed in patients who had low MGMT expression. CONCLUSIONS: The current data has suggested that half of the patients with progressive, regrowing NFPAs exhibit low MGMT expression and are potential candidates for treatment with TMZ. These findings provide a rationale for the use of TMZ as an alternative treatment approach in this subgroup if conventional therapy, including reoperation, radiosurgery, and radiotherapy, fails.

show abstract

MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy

Cited by 105 publications

References 11 publications

Treatment of pituitary neoplasms with temozolomide

Treatment of pituitary neoplasms with temozolomide

Errata

O⁶‐methylguanine DNA methyltransferase immunoexpression in nonfunctioning pituitary adenomas

Contact Info

Product

Resources

About

MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy

Cited by 105 publications

References 11 publications

Treatment of pituitary neoplasms with temozolomide

Treatment of pituitary neoplasms with temozolomide

Errata

O6‐methylguanine DNA methyltransferase immunoexpression in nonfunctioning pituitary adenomas

Contact Info

Product

Resources

About

O⁶‐methylguanine DNA methyltransferase immunoexpression in nonfunctioning pituitary adenomas