Odelia Cooper1, Vivien Bonert1, Adam N Mamelak1,2, Serguei Bannykh3, Shlomo Melmed1. 1. Pituitary Center, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA. 2. Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA. 3. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Abstract
BACKGROUND: Predictive markers of aggressive pituitary tumors have not been consistently demonstrated. Dural invasion and invasion-associated proteins, including matrix metalloproteinase-9 (MMP9) and cofilin, have been proposed to predict aggressive behavior and recurrence, but findings to date have been inconsistent. OBJECTIVE: To assess whether microscopic dural invasion predicts aggressive pituitary adenoma behavior and whether MMP9 and cofilin expression correlates with pathological and clinical invasion markers. METHODS: We retrospectively studied 328 consecutive pituitary mass resections by a single neurosurgeon at a single center; 254 were adenomas, and 98 had dural biopsies sent for routine pathological evaluation. Assessments included clinical features, postoperative course, and immunochemical expression of MMP9, cofilin, and phospho-cofilin. Recurrence was evaluated in those with at least 12 months of postoperative follow-up. RESULTS: Dural invasion was evident in 48% of biopsy specimens and was associated with male sex, larger tumors, suprasellar extension and sphenoid sinus invasion, cranial nerve palsies, and hypogonadism. Recurrence rates and the expression of MMP9, cofilin, and phospho-cofilin did not differ between those with and without dural invasion. However, differential expression of phospho-cofilin was associated with growth hormone deficiency and compressive pituitary mass effects. CONCLUSION: Dural invasion is associated with larger tumors, suprasellar and sphenoid sinus invasion, and pituitary failure but is not predictive of a more aggressive postoperative course. Routine dural biopsy is therefore of limited benefit in predicting postoperative recurrences. Cofilin expression may be an adjunctive biomarker of invasion in recurrent tumors, but MMP9 expression does not predict tumor behavior.
BACKGROUND: Predictive markers of aggressive pituitary tumors have not been consistently demonstrated. Dural invasion and invasion-associated proteins, including matrix metalloproteinase-9 (MMP9) and cofilin, have been proposed to predict aggressive behavior and recurrence, but findings to date have been inconsistent. OBJECTIVE: To assess whether microscopic dural invasion predicts aggressive pituitary adenoma behavior and whether MMP9 and cofilin expression correlates with pathological and clinical invasion markers. METHODS: We retrospectively studied 328 consecutive pituitary mass resections by a single neurosurgeon at a single center; 254 were adenomas, and 98 had dural biopsies sent for routine pathological evaluation. Assessments included clinical features, postoperative course, and immunochemical expression of MMP9, cofilin, and phospho-cofilin. Recurrence was evaluated in those with at least 12 months of postoperative follow-up. RESULTS: Dural invasion was evident in 48% of biopsy specimens and was associated with male sex, larger tumors, suprasellar extension and sphenoid sinus invasion, cranial nerve palsies, and hypogonadism. Recurrence rates and the expression of MMP9, cofilin, and phospho-cofilin did not differ between those with and without dural invasion. However, differential expression of phospho-cofilin was associated with growth hormone deficiency and compressive pituitary mass effects. CONCLUSION: Dural invasion is associated with larger tumors, suprasellar and sphenoid sinus invasion, and pituitary failure but is not predictive of a more aggressive postoperative course. Routine dural biopsy is therefore of limited benefit in predicting postoperative recurrences. Cofilin expression may be an adjunctive biomarker of invasion in recurrent tumors, but MMP9 expression does not predict tumor behavior.
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