EXPRESSION OF AMPHIPHYSIN-I, AN AUTOANTIGEN OF PARANEOPLASTIC NEUROLOGICAL SYNDROMES, IN BREAST-CANCER

Amphiphysin I is a 128 kD protein highly concentrated in nerve termina ls, where it has a putative role in endocytosis. It is a dominant auto antigen in patients with stiff-man syndrome associated with breast can cer, as well as in other paraneoplastic autoimmune neurological disord ers. To elucidate the connection between amphiphysin I autoimmunity an d cancer, we investigated its expression in breast cancer tissue. We r eport that amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-amphiphysin I antibodie s and paraneoplastic sensory neuronopathy. Amphiphysin I was also dete ctable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a varie ty of other non-neuronal tissues. The predominant amphiphysin I isofor m expressed outside the brain in humans is the 108 kD isoform which re presents an alternatively spliced variant of neuronal amphiphysin I mi ssing a 42 amino acid insert. Our study suggests a link between amphip hysin I expression in cancer and amphiphysin I autoimmunity. The enhan ced expression of amphiphysin I in some forms of cancer supports the h ypothesis that amphiphysin family members may play a role in the biolo gy of cancer cells.