Collagen crosslinking and desmoplasia in oral squamous cell carcinoma: immunohistochemical approach to matrix stiffness with relation to tumor progression and metastasis

Abstract Background Most treatment modalities of oral squamous cell carcinoma (OSCC) were cancer cell-centered in the last decades. Nowadays, the attention is attracted toward tumor mechanobiology especially collagen remodeling processes. Lysyl oxidase (LOX) is a collagen crosslinking enzyme detected in various human cancers exhibiting early metastasis and worse prognosis. Furthermore, desmoplastic tumors showed more aggressive behavior and rapid progression. Role of collagen crosslinking and desmoplasia with consequent matrix stiffness in OSCC is still unclear. Aim To assess the intensity and localization pattern of LOX expression as collagen crosslinking enzyme and the degree of desmoplasia as indicators of matrix stiffness in OSCC with relation to histological grade and lymph node (LN) status. Materials and methods Thirty-six archived, formalin-fixed, paraffin-embedded OSCC specimens with and without LN metastasis were stained both immunohistochemically for LOX expression and also by Masson trichrome for collagen content. Image analyzer software was used to assess LOX intensity and surface area% of Masson trichrome-stained collagen. Results All cases with different OSCC grades showed nuclear LOX expression, with a reported significant inverse correlation between the cytoplasmic expression and the histological grades, the cytoplasmic LOX immunoexpression is lost with advanced OSCC grades. Thus, significant direct correlation between LOX intensity and degree of OSCC differentiation was recorded. The higher the degree of tumor differentiation, the higher the intensity of LOX immunoreaction was. Nuclear LOX expression in primary tumors was directly proportional to increased histological grade and LN metastasis, as with the restricted nuclear expression, the liability of metastasis increased. Additionally, remarkable direct significant correlation was noted between collagen content and the histological OSCC grades as well as LN metastasis, the poorly differentiated OSCC revealed the highest collagen density as well as LN metastasis. Conclusion Uniform restricted nuclear LOX pattern and the loss of cytoplasmic one in addition to degree of desmoplasia could be prognostic indicators of tumor aggressiveness and predictors of subtle LN metastasis rather than LOX intensity. LOX expression and desmoplasia signifies the role of matrix stiffness in OSCC progression.