Session: SUN 17-28-Adrenal Tumors & Pheochromocytoma
Poster Board SUN-19
Patients and Methods: Fourteen ACP patients, including 8 children (57% male; median age 15.5 yrs) were analyzed. Pituitary hormone deficiency and b-catenin mutations were found in 86% and 50% of these cases, respectively. The mRNA expression levels of SHH pathway genes (SHH, PTCH, SMO, GLI1, GLI2, GLI3, SUFU and ZIC2) was evaluated by qPCR. SMO, GLI1, GLI3 and SUFU protein expression was evaluated by immunohistochemistry (IHC). Seven normal pituitaries tissues were used as controls.
Results: Compared to normal pituitaries, ACP presented extremely higher mRNA levels of SHH (fold: 4.6x103; p<0.01) and GLI1 (fold: 1.2x103; p<0.001) and higher GLI3 mRNA levels (fold: 17; p<0.001). Interestingly, ACP GLI2 mRNA expression level was not different of normal pituitaries (fold: 2.6; p=0.09). PTCH, SMO, ZIC2 and SUFU ACP mRNA levels were similar to normal pituitaries. Moreover, compared to beta-catenin WT, beta-catenin mutated ACPs presented higher expression of GLI1 (fold: 32; p=0.04) and SMO(fold: 5; p=0.03). We did not find association between abnormal ACP SHH pathway genes expression and age at diagnosis or disease progression, suggesting that SHH pathway abnormalities may occur at an early stage of tumor formation. IHC showed that normal pituitaries (4 adults; 3 children) present focal and weak expression of SMO, GLI1, GLI3 and SUFU. SMO, GLI1, GLI3 and SUFU immunostaining was found in 90%, 80%, 92% and 67% of the ACP evaluated.
Conclusions: Increased expression of SHH pathway genes suggests that SHH pathway is up-regulated in human ACP and may play an important role in the pathogenesis of these tumors.
Nothing to Disclose: SRA, DCG, LFL, CEJ, RSO, CEM, ACM, HRM, FPS, LN, MD, SRA
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