Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features

Abstract

Background: Anaplastic lymphoma kinase (ALK) mutations have been identified as a prominent cause of some familial and sporadic neuroblastoma (NB). ALK expression in NB and its relationship with clinical and histopathological features remains controversial. This study investigated ALK expression and its potential relations with these features in NB.

Methods: Ninety cases of NB at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam from 01/01/2018 to 12/31/2021, were immunohistochemically stained with ALK (D5F3) antibody. The ALK expression and its relations with some clinical and histopathological features were investigated.

Results: The rate of ALK expression in NB was 91.1%. High ALK expression (over 50% of tumor cells were positive with moderate-strong intensity) accounted for 65.6%, and low ALK expression accounted for 34.4%. All the MYCN-amplified NB patients had ALK immunohistochemistry positivity, most cases had high ALK protein expression. The undifferentiated subtype of NB had a lower ALK-positive rate than the poorly differentiated and differentiated subtype. The percentages of ALK positivity were significantly higher in more differentiated histological types of NB (p = .024). There was no relation between ALK expression and: age group, sex, primary tumor location, tumor stage, MYCN status, clinical risk, Mitotic-Karyorrhectic Index, prognostic group, necrosis, and calcification.

Conclusions: ALK was highly expressed in NB. ALK expression was not related to several clinical and histopathological features. More studies are needed to elucidate the association between ALK expression and ALK gene status and to investigate disease progression, especially the oncogenesis of ALK-positive NB.

Keywords: Anaplastic lymphoma kinase; Neuroblastoma.

Fig. 1.

(A) Neuroblastoma (left side) and normal adrenal gland (right side). (B) Strong immunohistochemistry staining of anaplastic lymphoma kinase (ALK) in tumor cells (left side), no ALK staining is found in normal adrenal tissue (right side).

Fig. 2.

(A) Immunohistochemistry (IHC) staining for anaplastic lymphoma kinase (ALK) in neuroblastoma (NB) showed strong, homogeneous cytoplasmic or membraned staining. (B) Moderate ALK IHC staining in NB. (C) Weak, heterogenous ALK IHC staining in NB.