Page 108 - New epidemiological and PSMA-expression based paradigms in salivary gland tumors

106
Chapter 6
transmembrane glycoprotein of the prostate secretory acinar epithelium. Its expression has been reported in normal as well as benign and malignant prostate tumor tissue, with upregulation in advanced prostate carcinoma and metastasis [14–16].
Organ specificity of PSMA: The original assumption of specific binding to prostate epithelium [14,17] was challenged beginning in 1995 after the identification of PSMA epitopes on cells in other organs. Other sites with proven expression include salivary glands, nervous system glia (astrocytes and Schwann cells), kidneys (proximal tubules), the small bowel (jejunal brush border), ductal epithelium of normal breasts, and skeletal muscle [18–21]. The exact function of PSMA in the prostate and kidneys is unclear, although there is suggestive evidence that it may be involved in the metabolism of folate [22]. PSMA was identified not only in healthy tissue, but also in neoplasms, including subtypes of schwannoma and bladder carcinoma [23]. Subsequently, it has been found in the neovascular capillary endothelium of a wide spectrum of solid tumors, i.e., epithelial tumors (carcinomas); neuroendocrine tumors; mesenchymal tumors (soft tissue sarcomas), and melanoma and glioma, which might suggest PSMA involvement in angiogenesis of developing neoplasms [21,24]. Recently, PSMA-ligand uptake and immunohistochemical expression were described in recurrent and distant metastatic adenoid cystic carcinoma and squamous cell carcinoma of the base of the tongue [25,26].
PSMA in imaging: In 1990 the PSMA specific immunoconjugate CYT-356, derived from the prostate-reactive monoclonal antibody 7E11-C5, was labelled with Indium-111 to visualize primary prostate tumors and their metastases using radioimmunoscintigraphy [17]. In recent years, urea-based small-molecule PSMA-inhibiting ligands were developed that could be coupled to 68Ga, with the currently most commonly applied ligand being Glu-NH-CO-NH-Lys(Ahx) coupled to the chelator HBED-CC. This allowed functional imaging with PET. Combined with CT, the imaging modality became known as PSMA PET/CT [27]. This new diagnostic tool is increasingly being used for detection and (re)staging of prostate cancer, with high sensitivity and specificity and with high impact on clinical management of these patients [28].
Expression of PSMA in salivary glands: Histopathological expression of PSMA has not been extensively described. Wolf et al., using immunohistochemical staining, reported that PSMA in human salivary gland specimens is expressed on the epithelium of acinar glandular cells and not the duct cells [29]. Our