The need for microdissectional tumor cell preparation during the moleculargenetic analysis of prostate cancer

For clinically localized prostate cancer, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a h ighly aggressive subgroup of prostatic tumors associated with decreased rec urrence-free and long-term survival following radical prostatectomy. Howeve r, several questions regarding the determination of p53 alterations in pros tate cancer, such as the poor correlation between immunohistochemistry and molecular genetic analysis, remain to be clarified. On the DNA level, p53 g ene alterations have been identified in only up to 64% of tumors exhibiting immunohistochemically detected overexpression of the p53 oncoprotein. This discrepancy can be explained either by the genetic microheterogeneity of p rostate cancer or by stabilization of the wildtype protein due to posttrans lational events. In the present study we tried to determine the concordance between an immunohistochemically detected p53 overexpression and the resul t of molecular genetic analysis. Therefore, tumor tissue obtained by microd issection from 40 prostate cancer specimens was subjected to DNA-sequence a nalysis. Microdissection was based either only on histopathologic criteria or on the result of the immunohistochemical staining reaction. In 8 of 14 ( 57%) tumors a positive immunohistochemical reaction could be confirmed by D NA sequencing, which revealed a missense point mutation at the p53 gene loc us, mainly in the form of G --> A transversion in exon 5 of the p53 gene. F ollowing the micropreparation of tumor cells exhibiting p53 oncoprotein ove rexpression, missense point mutation could be detected in an additional 4 c ases. Following a microscopically guided tumor cell dissection according to the result of immunohistochemistry, DNA sequencing confirmed an immunohist ochemically detected p53 overexpression in 86% of cases investigated. This result indicates that a micro-dissectional tumor cell preparation is recomm ended for molecular genetic analysis of histologically heterogeneous tissue specimens such as prostate cancer and should be performed according to and in addition to the result of immunohistochemistry when an immunohistochemi cal approach is available.