Expression of CXCR4 and CXCL12 and their correlations to the cell proliferation and angiogenesis in mycosis fungoides.

INTRODUCTION: Chemokines play an important role in tumor growth, invasion and metastasis. The CXCR4/CXCL12 axis has been implicated in development of both solid tumors and hematological malignancies and is also relevant in the pathogenesis of the most common primary cutaneous T-cell lymphoma, mycosis fungoides (MF). AIM: To evaluate the expression of CXCR4 and CXCL12 in MF and to examine their associations with cell proliferation and angiogenesis. MATERIAL AND METHODS: The material for the study consisted of skin samples obtained from 56 patients with MF and 20 healthy volunteers. The expression of CXCR4 and CXCL12 was assessed by immunohistochemistry on the paraffin blocks and compared to the expression of angiogenesis marker (CD34) and proliferation indicators (Ki-67, AgNORs). RESULTS: The expression of chemokine CXCL12 and its receptor CXCR4 was significantly higher in MF than in the healthy skin (p < 0.001). There was no significant difference between early and advanced stages of MF. Similarly, there was no statistically important correlation between the expression of CXCR4/CXCL12 and angiogenesis and proliferation markers, however a significant correlation between CD34 and AgNORs expression was found (p < 0.001). CONCLUSIONS: The CXCR4/CXCL12 axis seems to play an important role in MF development in the early as well as in the advanced stages of the disease. Therefore, the CXCR4/CXCL12 axis seems to be an interesting potential target for the future strategies of new drug development, giving hope for more efficacious therapies for mycosis fungoides.

[Prognostic significance of cyclin D1 and cyclin B expression in laryngeal squamous cell carcinomas treated with radiotherapy]. / Znaczenie prognostyczne ekspresji cykliny D1 i cykliny B u pacjentów z rakiem krtani leczonych radioterapia.

UNLABELLED: Cyclin B1 and cyclin D1 playing the role of regulatory subunits of cyclin-dependent kinases responsible for progression of cell cycle are involved in carcinogenesis of head and neck tumors. The aim of this study is to investigate their value for predicting clinical outcome after radiotherapy of laryngeal squamous cell cancer (LSCC). MATERIAL AND METHODS: The study included 50 patients with LSCC treated between the years 1998 and 2003 with radiotherapy. Tissue samples were studied immunohistochemically for detection of cyclin B1 and cyclin D1 and their expression were correlated with clinicopathological factors, local tumor control and patient survival. RESULTS: Accumulation of cyclin D1 and cyclin B1 were detected in 36% and 48% of tumors respectively. No relationship was observed between immunostaining for analyzed proteins and clinicopathologic factors. Cyclin B1 overexpression was associated with higher rate of locoregional recurrence. Five-year disease free survival rate for patients with cyclin B1 positive tumors was 73% v. 84% for cyclin B1 negative patients (p=0.005). CONCLUSION: The expression of cyclin D1 in LSCC does not seem to have a prognostic significance. Overexpression of cyclin B1 may be an indicator of the risk of locoregional recurrence in patient receiving radiotherapy. Thus cyclin B1 detected by immunohistochemistry can be useful for predicting outcome of radiotherapy in patients with LSCC.

Clinicopathologic significance and prognostic role of cyclin E and cyclin A expression in laryngeal epithelial lesions.

CONCLUSIONS: The determination of cyclin A expression might be helpful in the identification of laryngeal squamous cell cancer (LSCC) patients with increased risk of metastases. The results suggest that cyclin A may be a more informative marker for cell proliferation than Ki-67. Abnormalities of cyclin E and cyclin A may play an important role in LSCC development and progression; however, the expression of cyclin E does not seem to have prognostic significance. OBJECTIVE: The aim of the study was to elucidate a possible association between cyclin E and cyclin A expression and clinicopathologic factors and their potential role as prognostic markers for patients with laryngeal epithelial lesions. MATERIALS AND METHODS: Expression of cyclins E and A, and Ki-67 was examined immunohistochemically in a formalin-fixed, paraffin-embedded series of 46 LSCC; 23 epithelial dysplasias (ED); and 21 normal mucosae (NM). RESULTS: The mean labeling indices (LIs) for cyclin E in LSCC, ED, and NM were 10.6%, 4.9%, and 0%, and for cyclin A 27.2%, 17.5%, and 7%, respectively. In LSCC, a statistically significant correlation was found between enhanced cyclin A expression and a higher incidence of locoregional lymph node metastasis (p0.01). The enhanced expression of cyclin A was linked with cell proliferation in LSCC, ED, and NM. No association was observed between cyclin E and A and other clinicopathologic parameters or applied treatments. The prognostic significance of cyclin E, cyclin A, and Ki-67 in determining overall survival time showed no statistically significant differences.