Erythropoietin and erythropoietin receptor system in a large uterine myoma of a patient with myomatous erythrocytosis syndrome: possible relationship with the pathogenesis of unusual tumor size

The rare condition of women with erythrocytosis and a concurrent myomatous uterus has been classified as “myomatous erythrocytosis syndrome”. Substantial myoma size has been noted as a common denominator in this condition in which recent evidence have confirmed erythropoietin (Epo) production by myoma tissues themselves. Apart from its primary endocrine role in controlling erythropoiesis, Epo has been demonstrated to mediate several cellular processes such as angiogenesis, mitogenesis, and inhibition of apoptosis by autocrine and paracrine mechanisms. Recently, Epo and its receptor (Epo-R) have been shown to be involved in the growth, viability, and angiogenesis of several malignant tumors including human female reproductive organ malignancies. In this paper, we researched on Epo and, as a first in the literature, Epo-R immunoexpression in a large uterine myoma of a term pregnant patient suffering from the myomatous erythrocytosis syndrome. Eight nongravidic leiomyomas and 8 gravidic leiomyomas were used as control group samples. Apart from confirming Epo production by myoma smooth muscle cells in the myomatous erythrocytosis syndrome, we reveal in this pathologic condition a characteristic strong Epo-R expression in myoma endothelial cells and a weak and sporadic Epo-R expression in myoma smooth muscle cells. The striking presence of Epo-R within myoma tissues in the case of the myomatous erythrocytosis syndrome allows us to speculate that myoma Epo production, besides determining erythrocytosis through systemic effects, may contribute, acting by autocrine and paracrine mechanisms, in determining the large myoma size almost always observed in this condition. Finally, we confirm a less but specific immunostaining for Epo in uterine myomas of patients without erythrocytosis and, as a first in the literature, we prove a weak and sporadic Epo-R expression in these lesions. These last results may contribute to knowledge of the yet unclear etiopathogenesis of the most common human gynecologic neoplasm.