Aberrantly expressed recoverin in tumor tissues from gastric cancer patients

A variety of neurological symptoms characterizing paraneoplastic syndromes, such as Lambert-Eaton myasthenic syndrome and paraneoplastic cerebellar degeneration, are well known to be associated with malignant neoplasms even though there is no evidence of nervous system invasion [1]. The possible pathogenesis is an autoimmune reaction toward aberrantly expressed neuron-specific antigens in cancer cells that presumably triggers immunological responses and causes neuronal cell degeneration. Cancer-associated retinopathy (CAR) has been identified as an ocular manifestation of paraneoplastic syndrome [2]. CAR is frequently found in patients with small cell carcinoma of the lung and other malignancies, and is clinically characterized with retinitis pigmentosa-like retinal degeneration including photopsia, progressive visual loss with a ring scotoma, attenuated retinal arterioles, and abnormalities of the a-and b-waves of an electroretinogram (ERG) [3]. Histopathology has shown primarily a loss of photoreceptor cells [2]. In terms of CAR autoantigen, a photoreceptor-specific, 26-kDa calcium-binding protein called recoverin [4] and other retinal antigens were identified. Recoverin is known to play an important role in light and dark adaptation by regulating rhodopsin phosphorylation and dephosphorylation in a calcium-dependent manner [5]. Alternatively, recoverin is also known to be a highly immunogenic molecule and to experimentally cause uveoretinitis in rat by its immunization [6]. A mechanism that has been postulated for the apoptotic cell death of photoreceptor cells observed in CAR is that antirecoverin antibody generated by unknown mechanisms in some cancer patients penetrates into the photoreceptor cells via the peripheral circulation and causes misregulation of the phototransduction pathway by blocking recoverin function [7].