Recognition of lysyl oxidase as a potential predictive biomarker for oral squamous cell carcinoma: an immunohistochemical study

BACKGROUND: Lysyl oxidase (LOX) is a copper amine oxidase which belongs to the LOX multigene family and is normally involved in cross-linking of stromal collagen fibers. LOX expression has been found to be associated with increased episodes of recurrence, metastasis and overall poor prognosis in renal cell carcinomas and melanomas. This study aimed to assess the effects of LOX on the prognosis of oral squamous cell carcinoma (OSCC), which is one of the most common cancers in India. METHODS: The immunohistochemical expression of lysyl oxidase using LOX2 primary antibody was assessed at the tumor proper, invasive tumor front and peritumoral stroma in tissue sections from 40 cases of histologically proven OSCC. RESULTS: LOX expression was elevated in OSCC patients who had lymph node metastasis and in those who died of disease. No significant variation was seen with histological grade. CONCLUSIONS: LOX has a 'pro-neoplastic' effect as it modulates the host stroma to favor increasing tumor mass and worsening prognosis. Increased expression of LOX causes increased collagen fiber cross-linkage that stiffens the stromal matrix. This increases compressive stresses contributing to tissue hypoxia that elevates Rho GTPase-dependent cytoskeletal tension leading to erratic tumor cell morphogenesis that in turn confers motility to these cells resulting in metastasis. Inhibitors of LOX can potentially down-regulate LOX levels in the tumor micro-environment by controlling tissue hypoxia and curtailing the production of hypoxic LOX molecules.