Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation.
CD44 isoforms have been implicated in tumor progression and embryogenesis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD44 isoforms in comparison with nonmalignant adult and fetal renal tissues. Evaluations were performed by immunohistochemistry using CD44 isoform-specific monoclonal antibodies and by reverse transcriptase polymerase chain reactions (RT-PCR). In the nonmalignant kidney no CD44 variant isoforms were detected. There was a significant increase in expression of CD44 standard (CD44s) and several variant isoforms (CD44v) in the course of tumor differentiation in clear cell carcinomas (n = 68) from stages G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD44-6v, and P < 0.007 for those containing CD44-9v). Also, in chromophilic cell carcinomas (n = 13), CD44 isoform expression correlated with grading; ie, no CD44 expression was detected in G1 tumors, whereas in approximately 50% of the G2 tumors, CD44s, CD44-6v, and CD44-9v isoforms were present. Oncocytomas (n = 8), which are benign renal cell tumors, did not express CD44 isoforms, whereas invasive chromophobe cell carcinomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript analyses by RT-PCR revealed that the upregulated isoforms in the carcinoma cells contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In conclusion, expression of variant CD44 isoforms was strongly correlated with grading and appears to mediate a more aggressive phenotype to renal cell tumors.
Terpe
H J
HJ
Zentrum für Pathologie, Justus-Liebig-Universität, Giessen, Germany.
Störkel
S
S
Zimmer
U
U
Anquez
V
V
Fischer
C
C
Pantel
K
K
Günthert
U
U
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000469:Alkaline Phosphatase / Q000276:immunology; D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012189:Retrospective Studies
D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000469:Alkaline Phosphatase