OBJECTIVE: This study was undertaken primarily to research transforming growth factor beta 1 (TGF-beta 1) and Wnt inhibitory factor 1 (WIF1) for the prediction of nonfunctioning pituitary adenoma (NFPAs) invasion and recurrence of tumor samples and the relations between quantitatively determined markers and clinical characters. METHODS: We studied 104 patients, including 59 patients without recurrence and 45 patients with recurrence (9 patients with one surgery and 36 patients operated twice, both tumors being studied). All tissues were immunostained for TGF-beta 1 and WIF1 using tissue microarrays and confirmed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: We found that invasion, TGF-beta 1, and WIF1 were significantly associated with recurrence and that age was associated with low expression of TGF-beta 1 and WIF1 (P < 0.001). There were no statistically significant differences in the expression of the 2 proteins between the noninvasive and the invasive groups. The expression of TGF-beta 1 and WIFI in primary tumors in the recurrence group was lower than in the nonrecurrence group (P < 0.001). In the 36 paired primary or recurrent tumors, the expression of TGF-beta 1 and WIF1 in recurrent tumors was higher than the expression of primary tumors, which was confirmed with qRT-PCR and Western blot. Therefore, TGF-beta 1 and WIF1 seem to be related to recurrence or progression of pituitary adenomas. CONCLUSIONS: The expression of TGF-beta 1 and WIF1 in NFPAs correlated with cell proliferation and recurrence potential. They may be good markers of progressive behavior in NFPAs; however, the biologic mechanism needs further study.