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Predicting Recurrence of Nonfunctioning Pituitary Adenomas

Endocrinology (T.-W.N., E.J.L.), Pituitary Tumor Clinic and Institute of Endocrinology (T.-W.N., S.H.K., E.J.L.), and Pathology, Yong-Dong Severance Hospital (H.J.J.), Pathology Ilsan Hospital (M.-K.L.), Pathology (T.S.K.), and Neurosurgery (S.H.K.) and Yonsei Brain Research Institute, Yonsei University College of Medicine, 120-752 Seoul, Korea

Address all correspondence and requests for reprints to: Eun Jig Lee, M.D., Ph.D., Endocrinology, Yonsei University College of Medicine, 250 Seongsanno, Sudaemoon-gu, 120-752, Seoul, Korea. E-mail: ejlee423{at}yuhs.ac. OR Sun Ho Kim, M.D., Ph.D., Neurosurgery, Yonsei University College of Medicine, 134 Seongsanno, Seodaemun-gu, 120-752, Seoul, Korea. E-mail: sunkim{at}yuhs.ac.

Context: Nonfunctioning pituitary adenomas are commonly diagnosed as large tumors. Most are detected incidentally during imaging studies or as a result of neurological manifestations. Depending on severity, most patients with large tumors require surgery and adjunctive therapies because of the high rate of tumor recurrence. The ability to predict the recurrence of a tumor at the time of the initial surgery would be helpful in deciding whether adjunctive therapy is necessary and decreasing morbidity. We investigated the use of several cellular markers for predicting the recurrence of nonfunctioning pituitary adenomas.

Objective: A tissue array block was made using tissue from 35 cases of nonfunctioning pituitary adenomas (16 cases with early recurrence 4 yr after surgery, 10 cases with late recurrence >4 yr after surgery, and nine cases without recurrence). Levels of tumor tissue cellular markers associated with cell proliferation or apoptosis were analyzed, and immunohistochemical study of cellular markers was conducted using sectioned slides from the tissue array block.

Results: High Ki-67 and TUNEL labeling indexes were associated with recurrent nonfunctioning pituitary adenomas. Tumors with a high level of expression of phospho-Akt, phospho-p44/42 MAPK, and PTTG1 were associated with early recurrence. However, high levels of expression of phospho-CREB and ZAC1 were inversely associated with recurrence.

Conclusions: Tumors with high levels of expression of phospho-Akt and phospho-p44/42 MAPK and low levels of expression of phospho-CREB and ZAC1 should be followed closely and may require adjunctive therapy to prevent tumor recurrence.