Expression and prognostic value of epidermal growth factor receptor, transforming growth factor-alpha, and c-erb B-2 in nephroblastoma.
BACKGROUND
Wilms tumor is one of the most common solid tumors in children. A transforming growth factor-alpha (TGF-alpha)/epidermal growth factor receptor (EGF-R) autocrine loop plays an important role in tumor growth. Abnormal expression of TGF-alpha, EGF-R and c-erb B-2 has been demonstrated in several human malignancies.


METHODS
The immunohistochemical expression of TGF-alpha, EGF-R, and c-erb B-2 was studied in paraffin material of 62 clinical Wilms tumors. Patients had a mean follow-up of 5.7 years.


RESULTS
Generally, TGF-alpha, EGF-R, and c-erb B-2 were expressed in tissue of the normal kidney and at variable levels in the three cell types of Wilms tumor, i.e., blastemal, epithelial, and stromal cells. Immunoreactive blastema cells were found in 48%, 44%, and 34% of tumors for TGF-alpha, EGF-R, and c-erb B-2, respectively. It was found that TGF-alpha, EGF-R, and c-erb B-2 blastemal and epithelial expression gradually increased from T1 to T3. The blastemal expression of TGF-alpha was statistically significantly correlated with clinicopathologic stages. Both univariate and multivariate analysis showed that blastemal TGF-alpha expression was indicative for clinical progression, but neither blastemal TGF-alpha, nor EGF-R or c-erb B-2 expression correlated with patients survival. Epithelial staining was of no prognostic value. The simultaneous expression of TGF-alpha/EGF-R was indicative for clinical progression at univariate level.


CONCLUSIONS
Increased expression of TGF-alpha in the blastemal part of Wilms tumor correlated with tumor classification and clinical progression. These findings suggest that significant expression of TGF-alpha and EGF-R may play a role in promoting transformation and/or proliferation of Wilms tumor, perhaps by an autocrine mechanism. Therefore, their expression may be of value in identifying patients at high risk of tumor recurrence.
Ghanem
M A
MA
Department of Pediatric Urology, Josephine Nefkens Institute, Rotterdam, The Netherlands.
Van Der Kwast
T H
TH
Den Hollander
J C
JC
Sudaryo
M K
MK
Mathoera
R B
RB
Van den Heuvel
M M
MM
Noordzij
M A
MA
Nijman
R J
RJ
van Steenbrugge
G J
GJ
D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology*
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta