Immunohistochemical Expression of Angiogenesis-Related Markers in Oral Squamous Cell Carcinomas With Multiple Metastatic Lymph Nodes

Abstract

The aim of this study was to evaluate the histopathologic features and the expression of angiogenesis-related markers in primary tumors and metastatic lymph nodes of oral squamous cell carcinomas (SCCs) with multiple lymph node involvement in comparison with oral SCCs without nodal metastasis. The protein levels of the angiogenesis inhibitor endostatin, as well as those of the related molecules collagen XVIII, collagen-binding protein (CBP) 2/heat shock protein (HSP) 47, and cathepsin L, were evaluated by immunohistochemical analysis. Compared with nonmetastatic cases, primary tumors of the metastatic group exhibited significantly decreased protein levels of endostatin and its precursor collagen XVIII. Comparison between primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases. Angiogenesis is essential for tumor growth and metastasis; accordingly, the observed differences in the immunohistochemical expression of angiogenesis-related proteins in oral SCC with multiple lymph node involvement may provide an explanation for the increased metastatic potential of these tumors.

Cysteine cathepsins and stefins in head and neck cancer: an update of clinical studies

“…The comparable CB and CL immunohistochemical profiles were described in the study on oral cavity tumors by Vigneswaran et al, 23 whereas conflicting results from some other studies could have resulted from the differences in analytical procedures used (antigens, reagents), low sample numbers in some series, 24,25 and from the inherent biological characteristics of the site of tissue sampling (oral cavity vs. oropharynx vs. other tumor types). 6,7,27 The observed perinuclear cathepsin positivity mainly manifested intracellularly and on the membrane surface outside the tumor cells, was more consistent throughout the studies (Figure 5a).…”

“…[23][24][25][26] So far, to the best of our knowledge, stefins have not been subjected to immunohistochemical evaluation in any of the studies conducted on head and neck carcinomas. The results on spatial distribution of CB and CL immunoreactivity, with perinuclear positivity mainly manifested intracellularly and on the membrane surface outside the tumor cells, reflect their physiological role and are consistent throughout the studies.…”

“…The results on spatial distribution of CB and CL immunoreactivity, with perinuclear positivity mainly manifested intracellularly and on the membrane surface outside the tumor cells, reflect their physiological role and are consistent throughout the studies. [23][24][25][26] …”

Clinical significance of serum and tumor tissue endostatin evaluation in operable non-small cell lung cancer

“…Previously, higher collagen XVIII in tumor was found to be associated with worse prognosis in several malignancies (34). However, there were contradictory results (35,36). No correlation was found between endostatin expression in tumor tissue and NSCLC patient prognosis in a study from Korea, which was confirmed by our observation (37).…”

Metastasis of Head and Neck Squamous Cell Carcinoma

“…On the other hand, these results contradict with those of Homer et al (Homer, et al, 2002), who observed a positive trend between higher levels of endostatin and nodal metastasis and an association between increased endostatin expression and higher tumor grade, recurrence, and death in patients with HNSCC. The authors attributed this discrepancy to differences in methods used, as these investigators measured the circulating levels of endostatin, whereas this study assessed the levels in tissue samples (Nikitakis, et al, 2003).…”