P53 expression is significantly correlated with high risk of malignancy and epithelioid differentiation in GISTs. An immunohistochemical study of 104 cases.
BACKGROUND
Molecular analyses of the c-kit and PDGFRalpha genes have contributed greatly to our understanding of the development of gastrointestinal stromal tumors (GISTs), but little is known about their malignant potential. The aim of our study was to evaluate cell cycle regulators as potential prognostic markers in GISTs.


METHODS
We investigated 104 KIT positive GISTs from various tumor sites in immunoassays on CD34, Ki67 and particularly on P53, BCL-2 and Cyclin D1. The results were compared with tumor size, mitotic rate, proliferative activity, histological subtype, nuclear atypia and risk assessment according to Fletcher and Miettinen. Occurrence of metastases and survival were also taken into account.


RESULTS
The expression of P53 was significantly correlated with high risk criteria towards malignancy and epithelioid differentiation in GISTs. Likewise P53 label correlated significantly with the established prognostic indicators: tumor size, mitotic rate, nuclear atypia and proliferative activity. Regarding the site of tumor presentation, P53 was not a decisive factor. BCL-2 and Cyclin D1 expression was not related to any of the prognostic indicators.


CONCLUSIONS
The present data identified P53 being a recommendable marker for predicting the risk of malignancy in GISTs. In addition, we found P53 significantly correlated with epithelioid tumor differentiation, independent of tumor site. BCL-2 and Cyclin D1, however, did not prove to be deciding markers for diagnosis and prognosis.
Pauser
Ursula
U
Department of Pathology, University of Lübeck, Germany. upauser@gmx.de
Schmedt Auf der Günne
Nina
N
Klöppel
Günter
G
Merz
Hartmut
H
Feller
Alfred C
AC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53