Department of Endocrinology, Acibadem University School of Medicine, Istanbul, Turkey.
Altunizade Acıbadem Hastanesi, Altunizade Mahallesi, Yurtcan Sokagi No:1, Uskudar, 34662, Istanbul, Turkey.
Endocr Pathol. 2020 Jun;31(2):166-173. doi: 10.1007/s12022-020-09609-2.
The underlying mechanisms of aggressive pituitary neuroendocrine tumors (pitNETs) are still unclear. The p16 protein, encoded by the CDKN2A tumor suppressor gene on chromosome 9p21, is commonly reported to be lost in numerous types of cancer. For this reason, this study examined to examine the status of homozygous deletion of CDKN2A in high-risk pitNETs. Thirty-eight high-risk pitNETs (30 male, 8 female) were analyzed for CDKN2A deletion by fluorescent in situ hybridization (FISH). Demographic characteristics such as sex, patient age at operation, and sellar magnetic resonance imaging findings including tumor size and invasion status were recorded. The frequency of CDKN2A homozygous deletion by FISH was 3/38 (7.89%) in the high-risk pitNET group. All of these three cases with CDKN2A homozygous deletion were invasive densely granulated lactotroph tumors (p = 0.000). CDKN2A deletion was not correlated with patient age, sex, cavernous sinus invasion (CSI), and tumor size (p > 0.05). The Ki-67 proliferation index was significantly correlated with CDKN2A homozygous deletion (p = 0.003). The mean Ki-67 proliferation index was 10.7% in pitNETs with CDKN2A homozygous deletion and the Ki-67 proliferation index in the whole study group was 4.1%. CSI was significantly correlated with the morphofunctional tumor types including lactotroph tumor, invasive null cell tumor, and invasive gonadotroph tumor (p = 0.021). These findings suggest a close correlation between inactivation of p16 gene and invasive lactotroph tumors. Further investigations are needed to expand on the mechanism of p16 (CDKN2A) gene deletion in high-risk pitNETs.
侵袭性垂体神经内分泌肿瘤（pitNETs）的潜在机制尚不清楚。p16 蛋白由染色体 9p21 上的 CDKN2A 肿瘤抑制基因编码，在许多类型的癌症中通常报道丢失。出于这个原因，本研究检查了高危 pitNETs 中 CDKN2A 纯合缺失的状态。通过荧光原位杂交（FISH）分析了 38 例高危 pitNET（30 例男性，8 例女性）的 CDKN2A 缺失情况。记录了人口统计学特征，如性别、手术时患者年龄以及鞍磁共振成像（MRI）发现，包括肿瘤大小和侵袭状态。FISH 检测高危 pitNET 组中 CDKN2A 纯合缺失的频率为 3/38（7.89%）。这三个 CDKN2A 纯合缺失的病例均为侵袭性致密颗粒状催乳素细胞瘤（p=0.000）。CDKN2A 缺失与患者年龄、性别、海绵窦侵袭（CSI）和肿瘤大小无关（p>0.05）。Ki-67 增殖指数与 CDKN2A 纯合缺失显著相关（p=0.003）。CDKN2A 纯合缺失的 pitNETs 的 Ki-67 增殖指数为 10.7%，而整个研究组的 Ki-67 增殖指数为 4.1%。CSI 与形态功能肿瘤类型（催乳素细胞瘤、侵袭性无细胞肿瘤和侵袭性促性腺激素肿瘤）密切相关（p=0.021）。这些发现表明 p16 基因失活与侵袭性催乳素细胞瘤密切相关。需要进一步研究来阐明高危 pitNETs 中 p16（CDKN2A）基因缺失的机制。
