Expression of thymidine phosphorylase and cyclooxygenase-2 in melanoma

Abstract

Several studies have reported an increase in vascular structures in malignant melanoma. Neovascularization can be enhanced by several factors. Among them, thymidine phosphorylase (TP) and cyclooxygenase-2 (COX-2) have been reported to play a role. The expressions of TP and COX-2 were evaluated trough immunohistochemistry in a series of 78 primary cutaneous melanomas diagnosed between 2000 and 2004. The expressions of TP and COX-2 through mRNA and western blot analysis were also evaluated in several melanoma cell lines. TP expression and COX-2 expression were considered positive in 25 cases (32%) and 22 cases (28.2%), respectively. TP-positive melanomas showed a lower mitotic rate (P=0.008), smaller thickness (P=0.01), and absence of lymphovascular invasion (P=0.04). COX-2-positive melanomas showed a higher mitotic rate (P=0.01) and higher thickness (P=0.03). COX-2 expression was associated with reduced disease-free survival (P=0.01). COX-2-positive cases showed a trend toward reduced survival, whereas TP was not correlated with overall survival. COX-2 expression was detected in four of 11 melanoma cell lines both by mRNA and by western blot analysis. Our data show that TP expression is associated with more favorable prognostic factors (such as thin melanoma, low mitotic count, and absence of lymphovascular invasion), whereas COX-2 expression is associated with poor prognostic factors (thicker melanoma and high mitotic count).

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

“…COX-2 expression has been found to be associated with an increased risk of tumor recurrence, advanced cancer stage and/ or poor overall survival in a large number of cancers such as ovarian cancer [28,29], osteosarcoma [30,31], pancreatic cancer [32], gastric cancer [33][34][35], classical Hodgkin's lymphoma [36], oral squamous cell cancer [37], melanoma [38], non-small cell lung cancer [39] but not lung adenocarcinoma [40], clear cell renal carcinoma [41], cervical cancer [42] and esophageal adenocarcinoma [43]. The specific expression of COX-2 in breast and colon cancers is detailed later in this article.…”

Immunohistochemical detectability of cyclooxygenase‐2 expression in cells of human melanocytic skin lesions: A methodological review

“…The results of the COX-2 expression studies using antibodies specific for the C-terminus of this protein are largely divergent. Soares et al 43 36,43,46 or in metastases 48 with the shorter patients' survival was demonstrated. However, in other studies, there was no significant correlation of the staining with analyzed clinico-pathological characteristics of melanoma 33,34,41 or it was undetectable in nevi, primary melanomas, 32 and even in metastases.…”

“…It allowed to find significant differences in the COX-2 expression between benign and malignant lesions and correlations with the most important prognostic factors in melanomas and patients' survival. [38][39][40][43][44][45][46][47][48][49] Such correlations were not found in two studies in which antibodies specific for the C-terminal fragment of the COX-2 protein were used and analysis of the fraction of stained cells alone was applied 41 or sum of scores assigned to the percentage of cells and the intensity of staining was calculated. 32 However, adding of parameters measured in different units is not acceptable and may lead to controversial results.…”

“…Greater consistency of the results occurs between the works in which the analysis is based on calculation of the percentage fraction of the COX‐2‐positive cells and/or on the use of algorithms that take into account both the percentage of stained cells and their staining intensity. It allowed to find significant differences in the COX‐2 expression between benign and malignant lesions and correlations with the most important prognostic factors in melanomas and patients' survival . Such correlations were not found in two studies in which antibodies specific for the C‐terminal fragment of the COX‐2 protein were used and analysis of the fraction of stained cells alone was applied or sum of scores assigned to the percentage of cells and the intensity of staining was calculated .…”

“…In addition, COX-2 expression level was higher in nodular melanomas than in superficial spreading ones and higher in melanomas being in vertical than those in horizontal growth phase. Minisini et al46 also described a statistically significant relationship of the elevated COX-2 expression with deeper Breslow thickness and with high mitotic index.…”