CDR2 antigen and Yo antibodies

Abstract

Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo antibodies that are directed against human cerebellar degeneration-related protein 2 (CDR2). Such antibodies may also be found in ovarian cancer patients without PCD. We studied if there was an association between Yo antibody production and differences in CDR2 cDNA sequence, mRNA or CDR2 expression in ovarian cancers. We found similar CDR2 cDNA sequence, mRNA and protein levels in primary ovarian cancers, with or without associated Yo antibodies. CDR2 was also present in other cancers, as well as in normal ovary tissue. The results suggest that Yo antibodies are not only related to the expression of CDR2 alone, but also to immune dysregulation.

Fig. 1

a Western blot shows CDR2 in four human ovarian cancer extracts (1–4), in lysates of human ovarian cancer (5), and human normal ovary tissue (6). b Western blot shows recombinant CDR2 as positive control (1), CDR2 in cell lines of lung cancer (2), ovarian cancer (3), neuroblastoma (4), and in human normal cerebellum (5), but not in human normal cerebrum (6)

Fig. 2

Staining with polyclonal antibody against CDR2 shows granular green staining mainly in the cytoplasm of cell lines of ovarian cancer (a) and lung cancer (b). DAPI stains the nuclei blue. A similar granular staining pattern was found in the cell line of cervical cancer using monoclonal antibody against CDR2 (c) and polyclonal antibody against CDR2 (d), but the staining was almost completely abolished after preincubation of the polyclonal antibody with recombinant CDR2 (e)

Fig. 3

Ovarian and colon cancer biopsies were stained with polyclonal antibody against CDR2. There was no binding of the secondary antibody alone to ovarian cancer (a). The same ovarian cancer from a patient with Yo antibodies, but no PCD showed CDR2 staining of cytoplasm and nuclei of the cancer cells (b). This biopsy also contained normal ovarian tissue with slight CDR2 staining of stromal cells and strong CDR2 staining of epithelial cell (c). Two other ovarian cancers from patients with PCD and Yo antibodies showed nuclear CDR2 staining of the cancer cells (d, e). Colon cancer cells also expressed nuclear and cytoplasmic CDR2 staining (f)