ABSTRACT
PURPOSE: To determine the prevalence and evaluate the possible prognostic value of the molecular targets in malignant melanoma, we studied the overexpression of HER-2/neu, c-Kit, and vascular endothelial growth factor (VEGF) in this patient population. MATERIALS AND METHODS: Overexpression of HER-2/neu, c-Kit, and VEGF was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Only two patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit and 42 (20.8%) specimens showed VEGF overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit-positive and c-Kit-negative groups (P = 0.36) and VEGF-positive and VEGF-negative groups (P = 0.25). Interestingly, c-Kit was more likely to be overexpressed in the superficial spreading type and VEGF was overexpressed preferentially in the amelanotic melanoma type. CONCLUSIONS: HER-2/neu has no role in melanogenesis. Both c-Kit (expressed in superficial spreading disease) and VEGF (expressed in amelanotic melanoma) may have significant therapeutic implications as molecular targets, which warrants further investigation.
Subject(s)
Biomarkers, Tumor/analysis , Melanoma/chemistry , Proto-Oncogene Proteins c-kit/analysis , Receptor, ErbB-2/analysis , Vascular Endothelial Growth Factor A/analysis , Biopsy , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Medical Records , Melanoma/diagnosis , Middle Aged , Retrospective Studies , Survival Analysis , Up-RegulationABSTRACT
BACKGROUND: Molecular changes associated with the transition of melanoma cells from radial to vertical growth phase are not defined. To evaluate the role of VEGF in melanogenesis and determine its possible diagnostic and prognostic implications, we analyzed overexpression of VEGF in 202 cases of melanoma. MATERIALS AND METHODS: Overexpression of VEGF was evaluated in 202 archival paraffin-embedded tissue specimens using an avidin-biotin immunohistochemical (IHC) assay. RESULTS: Of the 202 melanoma specimens, 42 (20.8%) showed evidence of VEGF overexpression on IHC testing. Multivariate analysis performed using Cox proportional hazards method did not show a statistically significant survival difference between the VEGF-positive and negative groups (p = 0.25). CONCLUSION: Although of no significant prognostic value, VEGF may have critical therapeutic implications as a molecular target since it is expressed in about 20% of melanomas. The role of target-specific therapies against VEGF in malignant melanoma warrants further investigations.
Subject(s)
Melanoma/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Melanoma/pathology , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Sex Factors , Survival RateABSTRACT
BACKGROUND: Mantle cell lymphoma (MCL) is a low-grade lymphoproliferative malignancy that is extremely refractory to chemotherapy. Commonly used treatments have yielded unfavorable response rates (30% complete remission). We evaluated the incidence of c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in patients with MCL in an effort to identify possible targets for therapeutic intervention. MATERIALS AND METHODS: Patients with a diagnosis of MCL based on CD5 positivity associated with cyclin D1 positivity and CD23 negativity on the lymph node/bone marrow specimen were included in our retrospective study. CD117 overexpression was performed using immunohistochemistry on archival specimens. VEGF expression was detected by the avidin-biotin-complex method. RESULTS: Between 1997 and 2001, we identified 17 patients with MCL (9 males, 8 females) with a mean age of 57 years (age range: 42-66 years). The mean overall survival was 34 months (range: 11-60 months). VEGF expression was identified in 7 out of 17 (41.18%) patients with MCL. Among the VEGF-positive patients (n = 7, 41.1%), the mean survival was 24 months (range: 11-42 months), while patients without VEGF expression (n = 10, 58.9%) had a mean survival of 44 months (range: 21-60 months). CD117 expression was identified in only 2 out of 17 (1.17%) patients in our study. CONCLUSION: Our study evaluated the role of c-kit and VEGF overexpression in MCL. Although CD117 may not be of therapeutic significance, target-directed signal transduction inhibition therapy using VEGF-inhibitors may be a distinct possibility in a select group of patients with MCL. Future larger studies are urgently needed to elaborate the role of VEGF in MCL.
