Abstract:
Defining biomarkers for invasive pituitary neuroendocrine tumors (PitNETs) is highly desirable. The high mobility group A (HMGA) proteins are among the most widely expressed cancer-associated proteins. Indeed, their overexpression is a frequent feature of human malignancies, including PitNETs. We show that nonfunctioning PitNETs (NF-PitNETs) express significantly higher levels of HMGA1 than somatotropinomas (GHs) and corticotropinomas (ACTHs). Furthermore, HMGA2 expression was detected only in NF-PitNETs and was significantly higher in larger tumors than in smaller tumors. HMGA expression analysis generally focuses on nuclear staining. Here, cytoplasmic HMGA staining was also found. PitNETs displayed strong nuclear HMGA1 and strong cytoplasmic HMGA2 immunoreactivity. Interestingly, the HMGA1 and HMGA2 nuclear expression levels were significantly higher in invasive adenomas than in noninvasive adenomas. The highest levels of nuclear HMGA2 were found in GHs. In conclusion, we show that overexpression of nuclear HMGA proteins could be a potential biomarker of invasive PitNETs, particularly HMGA2 for GHs. HMGA2 might be a reliable biomarker for NF-PitNETs.
摘要:
非常需要定义侵袭性垂体神经内分泌肿瘤(PitNETs)的生物标志物。高迁移率族A(HMGA)蛋白是最广泛表达的癌症相关蛋白之一。的确,它们的过度表达是人类恶性肿瘤的常见特征,包括pitnet。我们表明,无功能的PitNETs(NF-PitNETs)表达的HMGA1水平明显高于生长激素瘤(GHs)和促肾上腺皮质激素瘤(ACTHs)。此外,仅在NF-PitNETs中检测到HMGA2表达,并且在较大的肿瘤中明显高于较小的肿瘤。HMGA表达分析通常集中在核染色上。这里,还发现细胞质HMGA染色。PitNETs显示出强的核HMGA1和强的细胞质HMGA2免疫反应性。有趣的是,侵袭性腺瘤中HMGA1和HMGA2核表达水平显著高于非侵袭性腺瘤.在GHs中发现了最高水平的核HMGA2。总之,我们表明核HMGA蛋白的过表达可能是侵袭性PitNETs的潜在生物标志物,特别是GHs的HMGA2。HMGA2可能是NF-PitNETs的可靠生物标志物。