1型神经纤维瘤病相关周围神经鞘瘤中的ERBB2和ERBB3生长因子受体、神经调节蛋白-1、CD44和Ki-67增殖指数

ERBB2 and ERBB3 Growth Factor Receptors, Neuregulin-1, CD44 and Ki-67 Proliferation Index in Neurofibromatosis Type 1-associated Peripheral Nerve Sheath Tumors.

作者信息

Friedrich Reinhard E, Nörnberg Louisa K N, Hagel Christian

机构信息

Department of Oral and Craniomaxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany;

Institute of Neuropathology, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany.

出版信息

Anticancer Res. 2022 May;42(5):2327-2340. doi: 10.21873/anticanres.15712.

DOI:10.21873/anticanres.15712

PMID:35489721

Abstract

AIM

To characterize the growth pattern and antigen profile of peripheral nerve sheaths tumors (PNST) in a large series of tumors obtained from patients with neurofibromatosis type 1 (NF1).

MATERIALS AND METHODS

Tissue micro-array technique was applied to study 520 PNSTs of 385 patients with NF1 by immunohistochemistry for human epidermal growth factor receptors erb-b2 receptor tyrosine kinase 2 (ERBB2) and ERBB3, CD44, neuroregulin (NRG1) and proliferation index by Ki-67. PNSTs were classified as cutaneous neurofibroma (CNF) in 114 cases, diffuse neurofibroma (DNF) in 109, diffuse plexiform neurofibroma (DPNF) in 108, plexiform neurofibroma (PNF) in 110, and malignant PNST (MPNST) in 22.

RESULTS

The Ki-67 proliferation index was significantly higher in MPNST than in benign PNST (p<0.001). ERBB2 expression was significantly lower in PNST with diffuse growth than in PNF and MPNST (p<0.001). ERBB3 expression was also higher in PNF and MPNST (both p<0.001) than in diffuse PNST. NRG1 expression was significantly higher in PNF than in non-encapsulated benign PNST or MPNST (both p<0.001). Co-expression of ERBB2, ERBB3 and ligand NRG1 was rare, mainly observed in PNST with a plexiform component (in four PNFs, nine DPNFs, one CNF, and two MPNSTs). Expression of CD44 in contrast was significantly stronger in diffusely growing PNST than in PNF (p<0.001).

CONCLUSION

Growth factor receptors ERBB2 and ERBB3 were significantly up-regulated in PNF and MPNST. The antigen expression pattern of DPNF resembled that of benign PNST with diffuse growth pattern rather than that of encapsulated PNF. Differentiating PNST may be important for the assessment of neurofibroma progression, and for the expected impact of drugs currently used for tumor reduction.

摘要

目的

在从1型神经纤维瘤病（NF1）患者获得的大量肿瘤中，描述周围神经鞘瘤（PNST）的生长模式和抗原谱。

材料与方法

应用组织微阵列技术，通过免疫组织化学检测人表皮生长因子受体erb-b2受体酪氨酸激酶2（ERBB2）和ERBB3、CD44、神经调节蛋白（NRG1）以及Ki-67增殖指数，对385例NF1患者的520个PNST进行研究。PNST分为114例皮肤神经纤维瘤（CNF）、109例弥漫性神经纤维瘤（DNF）、108例弥漫性丛状神经纤维瘤（DPNF）、110例丛状神经纤维瘤（PNF）和22例恶性PNST（MPNST）。

结果

MPNST的Ki-67增殖指数显著高于良性PNST（p<0.001）。弥漫性生长的PNST中ERBB2表达显著低于PNF和MPNST（p<0.001）。PNF和MPNST中的ERBB3表达也高于弥漫性PNST（均p<0.001）。PNF中的NRG1表达显著高于非包膜性良性PNST或MPNST（均p<0.001）。ERBB2、ERBB3和配体NRG1的共表达很少见，主要见于具有丛状成分的PNST（4例PNF、9例DPNF、1例CNF和2例MPNST）。相比之下，CD44在弥漫性生长的PNST中的表达显著强于PNF（p<0.001）。