Expression of integrin receptors on 45 clinical neuroblastoma specimens

Abstract

Immunohistological expression of integrins has been analyzed on 45 neuroblastoma specimens representative of the different clinical and histological forms of the tumor. None of the specimens expressed the α₅ chain of the integrins. The β₁ chain was expressed on all specimens, the α₁ chain on 44 specimens and the α₃ chain on 42; the 4 specimens which lacked α₁ or α₃ were stage‐4 neuroblastomas. The α₂ chain was expressed on 18 specimens, and the α₆ chain on 17;15 reacted with both. Their reactivity was related to the maturation of the tumor rather than the stage of the disease: they were expressed on lowgrade, well‐differentiated specimens; stage 3‐4 neuroblastoma specimens analyzed at diagnosis were negative, but usually expressed both chains when analyzed after in vivo differentiation by chemotherapy. α_v reacted with 18 specimens and β₃ with 12, without strict relation with the stage of the disease and/or its degree of differentiation; 9 well‐differentiated specimens expressed the β₄ chain; only 4 well‐differentiated specimens expressed the α₄ chain. The 4 specimens which lacked α₁‐β₁ or α₃‐β₁ expression had n‐myc amplification, whereas those which expressed either α₄, β₄, β₃, or α_v had no amplification. Furthermore, the expression of the 3 heterodimers α₄‐β₁, α_v‐β₃ and α₆‐β₄ was essentially observed on primary tumors which developed in the mediastinum. The expression of α₂‐β₁ and α₆‐β₁ was observed on both n‐myc‐positive and ‐negative specimens. β₁ and α₃, were diffusely expressed on all counterparts of these tumors, from undifferentiated neuroblasts to ganglion and Schwann cells. The α₁ chain reacted with undifferentiated and intermediate neuroblasts as well as with Schwann cells, but ganglion cells were negative. α₂ and α₆ chains were negative on undifferentiated neuroblasts, variably expressed on intermediate neuroblasts, and restricted to Schwann cells in ganglioneuroma. The expression of α₄ and β₄ was restricted to Schwann cells. α_v and β₃ occasionally reacted with undifferentiated and intermediate neuroblasts; α_v was strongly positive on Schwann cells but negative on ganglion cells, whereas β₃ was positive on both neuronal and non‐neuronal populations.