Objective: LIV-1 is an estrogen-regulated gene involved in intracellular zinc transport. LIV-1 protein is found predominately within hormonally controlled tissues. In breast cancer, LIV-1 has been proposed as a marker of lymph node metastatic potential. In cancer cells LIV-1 may regulate: 1)zinc transport, altering growth, metabolism and activating kinase-signaling pathways; 2)matrix metalloproteinase-like properties promoting invasion. The reported presence of hormone receptors in salivary gland (SG) carcinomas prompted us to evaluate LIV-1 expression in normal, benign and malignant SG tissues. Methods: Two SG adenocarcinoma cell lines HSY and HSG were evaluated for LIV-1 protein and mRNA expression by Western blot and real-time RT-PCR, respectively. Immunohistochemistry with LIV-1 antibody assessed protein levels of 12-malignant and 4-benign SG tumors compared with normal SG tissues. Immunostains were graded for positivity (0 for 0%, 1 for <20%, 2 for 20-50% and 3 for >50%) and intensity (weak-moderate-strong). Results: LIV-1 mRNA and protein expression were detected in both cell lines. All seven-mucoepidermoid carcinomas showed LIV-1 immunopositivity, which varied by tumor grade: low-, intermediate- and high-grade tumors stained as 2-moderate/strong, 2-weak and 1-weak, respectively. Other carcinomas stained as follows: carcinoma ex-pleomorphic adenocarcinoma: 2-moderate; acinic cell adenocarcinoma: 3-moderate; adenoid cystic carcinoma: 3-strong; salivary duct carcinoma: 3-strong; adenocarcinoma NOS: 3-moderate; pleomorphic low grade adenocarcinoma: 2-moderate. Benign SG neoplasms were positive for LIV-1 and stained as follows: pleomorphic adenoma: 3-moderate; papillary cystadenoma: 3-strong; basal cell adenoma: 1-moderate; canalicular adenoma: 3-moderate. Normal SG showed consistent LIV-1 staining graded as 3-moderate. Conclusions: LIV-1 was expressed in all SG tissues studied, possibly in response to hormonal stimulation. Quantitative and qualitative staining differences among the studied tissues may be related to diverse composition, levels of hormonal stimulation and/or receptor expression, and degree of differentiation. LIV-1 protein expression may correlate with the histologic grade of mucoepidermoid carcinoma, possibly representing a marker of malignant potential.

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