Most patients are women and associated tumors are almost exclusively gynecologic (mainly ovarian) or breast cancers. Some women and men with various adenocarcinomas, transitional cell carcinoma of the bladder or lymphoma have been described.
Frequency of anti-Yo antibodies in patients with suspected paraneoplastic neurological syndromes (PNS) without evidence of cancer after >5 years of follow-up: 2%
Frequency of anti-Yo antibodies in patients with breast or gynecologic cancer without PNS: 2% with titers similar to those of patients with PNS.
Immunohistochemistry on frozen brain sections (human, monkey, rabbit, rat, mouse) (figure 1, 2).
Figure 1. Anti-Yo immunoreactivity in human cerebellum.
|Figure 2. Anti-Yo immunoreactivity in rat cerebellum.|
Several commercial tests using immunoblots of recombinant CDR62 protein. Immunoblot of cerebellar Purkinje cell extracts (figure 3).
Figure 3. Immunoblot of rat cerebellar extract probed with 3 different anti-Yo sera and a normal control.
Patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies usually do not harbor concurrent antibodies to other onconeuronal antigens.
Expression of the Yo-antigens is limited to cytoplasm of cerebellar Purkinje cells and brainstem neurons. Two antigens are recognized by anti-Yo antibodies, a major antigen of 62 kDa (CDR62, cerebellar degeneration-related 62 kDa protein) and a minor antigen of 34 kDa (CDR34). Using anti-Yo sera, three genes have been cloned (cdr 1-3). Cdr1 encodes the 34 kDa protein, the predicted amino acid sequence of which reveals an unsual structure composed of nearly identical hexapeptide repeats. Cdr2 encodes the CDR62 protein that contains a helix-leucine zipper dimerization domain that specifically binds to c-Myc thereby downregulating its activity. In addition, cdr2 suppresses the transcriptional activity and DNA binding of nuclear facto-kappa B (NF-?B) by an unknown mechanism. The neuron specific expression of cdr2 is regulated by a post-transcriptional mechanism. A third gene, cdr3, is 45% identical with cdr2 at the predicted amino acid level but has not been further studied. Yo-antigens are expressed in the tumors of all patients with anti-Yo antibodies. Expression in tumors from seronegative patients is more widespread than previously presumed.
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