Connexin expression by human granulosa cell tumors: Identification of connexin 32 as a tumor signature.

Human granulosa cell (GC)-tumors are assumed to arise from ovarian GCs but to what extent they resemble normal human GCs is not well established. We examined whether a prominent feature of normal GCs, expression of the major gap junctional protein connexin 43 (Cx43), was retained in 14 human GC-tumor samples. Immunohistochemistry revealed areas of strong staining side by side with areas of weak and/or no staining. If present, cytoplasmic and membrane-associated Cx43 staining occurred. In cells with reduced or absent Cx43, another Cx was found, Cx32. Cx32, which is absent from non-tumor GCs, was present in GC-tumor cells co-expressed in part with Cx43 at gap junctional plaques. Expression of Cx32 and Cx43 was confirmed by RT-PCR and sequencing in the majority of tumor samples. Thus GC-tumor cells are characterized by a partial or complete loss of Cx43 expression and expression of Cx32, which may be a marker for these rare tumors. It is possible that the pattern of Cxs may contribute to tumor formation and growth, as it may indicate aberrant and/or reduced cell-to-cell communication ability.