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Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma.
- Source :
-
Virchows Archiv : an international journal of pathology [Virchows Arch] 2001 Nov; Vol. 439 (5), pp. 628-35. - Publication Year :
- 2001
-
Abstract
- We analyzed the immunohistochemical expression of the metastasis-associated protein, CD44v3, in 46 primary human malignant melanomas (MMs). This is the first time that the v3 splice variant of CD44 was found to be expressed in human melanomas (15 of 46), ranging from 3% to 35% of the cell population in the positive tumors. The expression of CD44v3 was observed in tumors thicker than 1.0 mm, and one-third of these tumors proved to be positive irrespective of the thickness. Patients were followed for a minimum of 61 months. The onset of lymph node or organ metastases occurred not later than 58 months and 60 months, respectively. Of the 15 CD44v3 positive tumors, 14 were observed in the organ metastatic tumor group, comprising the majority of those cases (14 of 21), and this association proved to be statistically significant compared with the non-metastatic (P<0.05) and lymph-node metastatic cases (P<0.01). CD44v3 expression in melanoma was also confirmed at the protein and messenger (mRNA) level in several human melanoma cell lines using flow cytometry and reverse transcriptase polymerase chain reaction analysis. In parallel to CD44v3, MMP-2 expression (determined using immunohistochemistry) was significantly elevated (P<0.05) but only in the organ metastatic group of MM. The 5-year survival of patients having thicker tumors than 1.0 mm (where v3 expression occurred) who had CD44v3+ tumors was significantly lower than those of the negative ones (35.7% versus 68.2%, respectively; P=0.025). Finally, we observed that the CD44v3-expressing tumors were characterized by significantly higher MMP-2 expression than the CD44v3-negative tumors (P<0.001), indicating a possible correlation between CD44v3- and MMP-2-positive phenotype and the organ metastatic potential of MM.
- Subjects :
- Alternative Splicing
Female
Flow Cytometry
Fluorescent Antibody Technique, Indirect
Humans
Hyaluronan Receptors biosynthesis
Immunoenzyme Techniques
Male
Matrix Metalloproteinase 2 analysis
Matrix Metalloproteinase 2 biosynthesis
Melanoma chemistry
Melanoma genetics
Melanoma mortality
Melanoma secondary
Neoplasm Metastasis genetics
Neoplasm Metastasis pathology
Phenotype
RNA, Messenger metabolism
RNA, Neoplasm analysis
Reverse Transcriptase Polymerase Chain Reaction
Skin Neoplasms chemistry
Skin Neoplasms genetics
Skin Neoplasms mortality
Skin Neoplasms pathology
Survival Analysis
Survival Rate
Tumor Cells, Cultured
Hyaluronan Receptors genetics
Melanoma metabolism
Skin Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0945-6317
- Volume :
- 439
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Virchows Archiv : an international journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 11764382
- Full Text :
- https://doi.org/10.1007/s004280100451