Immunohistochemical expression of cyclooxy genase- 2 [COX - 2] and vascular endothelial growth factor [VEGF] in oral: premalignant lesions and squamous cell carcinoma

ABSTRACT

Squamous cell carcinoma [SCC] represents more than 90% of all head and neck cancers. It can arise de novo or from premalignant lesions. Seventy to ninety percent of all precancerous oral lesions have the potential to develop into malignant phenotype. Early detection and identification of the molecular changes that are responsible for tumor development and progression is of paramount importance in medical and surgical intervention with improved outcome. Angiogenesis is an essential condition for the development and proliferation of malignant tumors. Cyclooxygenase [Cox-2] as well as vascular endothelial growth factor [VEGF] are two epitopes among the different pro angiogenic molecules that have been investigated in literature in relation to tumor angiogenesis. The present study aimed at delineation of the molecular expression profile of Cox-2 and VEGF factors in oral cavity premalignant dysplatic lesions and SCC and its relation to tumor development, grade and stage of the tumor. Thirty cases were studied, which included 12 tongue lesions, 3 in the cheek and 15 in the palate and mandible. The studied cases were categorized into five oral premalignant cases [leukoplakia] and 25 cases of invasive SCC with six cases presented by metastatic cervical lymph nodes. Paraffin embedded tissues were processed and sections were immunohistochemically stained using Avidin Biotin peroxidase complex [ABC] with Cox-2 and VEGF [Ab-7] epitopes. Positive staining for Cox-2 was detected in 3 out of 5[60%] of precancerous oral lesions, but it appeared in 9 out of 25 [36%] of SCC cases. Total positivity for Cox-2 reached 40% [12 out of the 30 samples]. As regards VEGF immuno staining, positive reaction was detected in one out of 5 cases [20%] of precancerous lesions and in 12 out of 25 cases [48%] of malignant lesions. Total positive reaction for VEGF was seen in 13 out of the 30 samples examined [43%]. Expression of VEGF was almost of the same ratio in premalignant and grade I tumors [25% and 26%] respectively, but it was increased in grade II [85%] and grade III tumors [66%]. Correlation between VEGF staining and grading of the SCC showed a significant difference [p=0.018]. An interesting finding in this study, is the expression of both Cox-2 and VEGF markers in normal fibroblasts, inflammatory cells, minor salivary glandular epithelium as well as some endothelial cells. Co-expression of both Cox-2 and VEGF staining was significantly correlated [p=0.004]. The results of this study demonstrated a definite role for Cyclo-oxygenase and VEGF as two pro-angiogenic factors that proved to be existing in both oral premalignant and SCC tumors .The dysplastic epithelium nearby a tumor area or in leukoplakia lesion expressed both markers with increased ratio for Cox-2 than VEGF factor. There was a direct relationship between VEGF immunopositivity and increased SCC grade. Also,co-expression of Cox-2 and VEGF was significantly correlated. From the present study it can be concluded that, both Cox-2 and VEGF factors are expressed in oral premalignant as well as SCC lesions, but Cox-2 may have a role in early stages of tumorigenesis, while VEGF showed a clear existence in higher grades of SCC