Analysis of Ki67, HMGA1, MDM2, and RB expression in nonfunctioning pituitary adenomas

Abstract

Nonfunctioning pituitary adenomas (NFPAs) are the most prevalent type of pituitary macro-adenoma. Clarifying the relationship between NFPA markers and disease progression or recurrence could provide a basis for administration of adjuvant treatments. The present study examined the expression levels of high-mobility group (HMG)A1, Ki-67, mouse double minute 2 homolog (MDM2), and retinoblastoma (RB)with respect to NFPA recurrence. Immunohistochemistry was carried out using antibodies to Ki-67, MDM2, HMGA-1, and RB on tissue microarray slides of a cohort of 35 paired NFPA samples of primary and recurrence/regrowth tumors. Based on postoperative magnetic resonance imaging data, tumors were classified as recurrence (n = 20) included primary and recurrent tumors or regrowth (n = 15) included primary and regrowth tumors, which are paired. Protein expression was classified as negative or positive according to the H-score method and was analyzed with respect to clinical and pathological findings. MDM2-positive cases accounted for11/20 primary and 19/20 s recurrent tumors (χ2 = 8.533, P = 0.003), and 9/15 primary tumors and 15/15 s regrowth tumors (χ2 = 7.5, P = 0.006). MGA1-positive cases represented 9/20 primary tumors and 16/20 s recurrent tumors (χ2 = 5.227, P = 0.022), and 4/15 primary tumors and 12/15 s regrowth tumors (χ2 = 8.571, P = 0.003). There was no statistically significant difference in Ki-67 expression between primary and second recurrent/regrowth tumors although theKi67 labeling index was higher in the latter groups. RB was highly expressed in all groups with no significant difference between them. HMGA1 and MDM2 were more highly expressed in recurrence/regrowth cases of NFPA than in primary NFPA. HMGA1 and MDM2 are biomarkers and potential drug targets for NFPA treatment.

Nomogram predictive model of post-operative recurrence in non-functioning pituitary adenoma

“…other factors that influence the proliferation of pituitary adenomas, such as angiogenesis, growth factors, oncogenes, apoptosis, tumor suppressor genes, and hormone receptors, have been shown to be predictive factors (15,(19)(20)(21). In this study, our results indicated that age, tumor size, cavernous sinus invasion, sphenoid sinus invasion, and surgery extension were the significant risk factors that were used to build the nomogram.…”

“…Another study indicated that a Ki-67 labeling index (LI) above 2.2% should attract more attention and require shorter intervals of follow-up with early adjuvant therapy and magnetic resonance imaging (MRI) scans (14). In contrast, Yao et al showed no statistical significance of the Ki-67 LI in primary (n=20) or recurrent tumors (n=15) (15). Recently, Cheng et al demonstrated a predictive model for NFPA that could facilitate prognostic evaluation and guide early interventions (9).…”

Renal Epithelioid Angiomyolipoma Undergoing Aggressive Clinical Outcome: The MDM2 Expression in Tumor Cells of Two Cases

“…Overexpression of MDM2 has been reported in many malignant tumors (Momand et al 1998). In addition, MDM2 expression has been reported to be correlated with progression of tumors, such as nonfunctioning pituitary adenoma (Yao et al 2017). Increased MDM2 expression was more frequently detected in seminoma and embryonal carcinoma than intratubular germ cell neoplasia (Datta et al 2001).…”

MDM2 promotes the proliferation and inhibits the apoptosis of pituitary adenoma cells by directly interacting with p53

“…gene of p53, indicating that MDM2 may be a functional factor in pituitary adenoma [9]. Furthermore, Yao X et al found that MDM2 may be a biomarker and potential drug target for pituitary adenoma treatment [10]. However, the mechanism of MDM2 in pituitary adenoma has not been studied thoroughly and clearly.…”