EXPRESSION OF INTEGRIN RECEPTORS ON 45 CLINICAL NEUROBLASTOMA SPECIMENS

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 alpha-5 chain of the integrins. The beta-1 chain was expressed on all specimens, the alpha-1 chain on 44 specimens and the alpha-3 chain on 42; the 4 specimens which lacked alpha-1 or alpha-3 were stage-4 neuroblastomas. The alpha-2 chain was expressed on 18 specimens, and the alpha-6 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 low-grade, 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. alpha-v reacted with 18 specimens and beta-3 with 12, without strict relation with the stage of the disease and/or its degree of differentiation; 9 well-differentiated specimens expressed the beta-4 chain; only 4 well-differentiated specimens expressed the alpha-4 chain. The 4 specimens which lacked alpha-1-beta-1 or alpha-3-beta-1 expression had n-myc amplification, whereas those which expressed either alpha-4, beta-4, beta-3 or alpha-v had no amplification. Furthermore, the expression of the 3 heterodimers alpha-4-beta-1, alpha-v-beta-3 and alpha-6-beta-4 was essentially observed on primary tumors which developed in the mediastinum. The expression of alpha-2-beta-1 and alpha-6-beta-1 was observed on both n-myc-positive and -negative specimens. beta-1 and alpha-3 were diffusely expressed on all counterparts of these tumors, from undifferentiated neuroblasts to ganglion and Schwann cells. The alpha-1 chain reacted with undifferentiated and intermediate neuroblasts as well as with Schwann cells, but ganglion cells were negative. alpha-2 and alpha-6 chains were negative on undifferentiated neuroblasts, variably expressed on intermediate neuroblasts, and restricted to Schwann cells in ganglioneuroma. The expression of alpha-4 and beta-4 was restricted to Schwann cells. alpha-v and beta-3 occasionally reacted with undifferentiated and intermediate neuroblasts; alpha-v was strongly positive on Schwann cells but negative on ganglion cells, whereas beta-3 was positive on both neuronal and non-neuronal populations.