Thymidine phosphorylase and cycloxygenase-2 expression in malignant melanoma

Background: Cyclooxygenase-2 (COX-2) protein expression has been described in melanoma and it seems to be associated with tumor progression and angiogenesis. Thymidine phosphorylase (TP) is a proangiogenic factor overexpressed in several human malignancies; it is also involved in the multistep process that converts the prodrug capecitabine into 5-fluorouracile. Both enzymes could be induced by several factors and could represent potential target for anticancer treatments. The aim of the study was to evaluate COX-2 and TP expression in a cohort of primary malignant melanomas and to investigate the correlation between these enzymes and known prognostic factors. Methods: Immunoistochemical TP and COX-2 expression was evaluated in 35 consecutive paraffin-embedded samples of cutaneous melanoma diagnosed between 1999 and 2003. Pathologic features were reviewed by expert pathologists. Clinical data were retrieved from medical charts. TP and COX-2 mRNA expression and protein expression was evaluated in melanoma cell lines through RT-PCR and Western Blot. Results: TP and COX-2 were highly expressed in 11 and 11 cases, respectively. High TP expression was associated with 1 mm melanoma (p = 0.0005) and Clark levels I-III (p = 0.017). High COX-2 expression was significantly associated with decreased disease free survival in multivariate analyses (p= 0.029). No significant association between these two biomarkers and other classical prognostic features was evident; a marginal association between COX-2 expression and mitotic rate > 0/mm2 was evident (p = 0.06). TP expression in melanoma cell lines was low; conversely, COX-2 was differently expressed among cell lines. Conclusions: The present study showed an interesting association between TP expression and thin malignant melanoma. In addition, COX-2 expression resulted to be associated with worse outcome. Further molecular characterizations of this series of melanoma is ongoing. The potential role of TP and COX-2 as therapeutic targets in melanoma deserves further investigations

Exploratory predictive and prognostic factors in advanced breast cancer treated with metronomic chemotherapy. Anticancer Drugs

Primary adenocarcinomas of the gastrointestinal tract showing a diffuse thyroid transcription factor-1 (TTF-1)-positive immunostaining are extremely uncommon and this finding in the biopsy specimen could yield to misleading diagnosis of a metastatic lung tumor. We report the clinical and pathological features of 2 cases, occurring in a 62-year-old woman and in a 66-year-old man. The first one is a gastric adenocarcinoma with liver metastasis; the other one is a gallbladder adenocarcinoma discovered during the screening for the colorectal cancer. Both the neoplasms showed a diffuse TTF-1 positivity and both the patients did not have any evidence of lung cancer. Neither a gastric adenocrcinoma with diffuse TTF-1 expression nor a TTF-1-positive gallbladder adenocarcinoma has been described befor

Expression of thymidine phosphorylase and cyclooxygenase-2 in melanoma.

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)

Measures of outcome in metastatic breast cancer: insights from a real-world scenario.

No gold standard treatment exists for metastatic breast cancer (MBC). Clinical decision making is based on knowledge of prognostic and predictive factors that are extrapolated from clinical trials and, sometimes, are not reliably transferable to a real-world scenario. Moreover, misalignment between endpoints used in drug development and measures of outcome in clinical practice has been noted. The roles of overall survival (OS) and progression-free survival (PFS) as primary endpoints in the context of clinical trials are the subjects of lively debate. Information about these parameters in routine clinical practice is potentially useful to design new studies and/or to interpret the results of clinical research. This study analyzed the impact of patient and tumor characteristics on the major measures of outcome across different lines of treatment in a cohort of 472 patients treated for MBC. OS, PFS, and postprogression survival (PPS) were analyzed. The study showed how biological and clinical characteristics may have different prognostic value across different lines of therapy for MBC. After first-line treatment, the median PPS of luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2)-positive groups was longer than 12 months. The choice of OS as a primary endpoint for clinical trials could not be appropriate with these subtypes. In contrast, OS could be an appropriate endpoint when PPS is expected to be low (e.g., triple-negative subtype after the first line; other subtypes after the third line). The potential implications of these findings are clinical and methodological