gms | German Medical Science

Prostate cancer (PCA) is among most frequent tumours in industrialized nations and continuous research efforts are needed in order to better understand its development and progression. Epidemiological studies suggest factors in life style to contribute to tumour development. Linkage analyses point to hereditary prostate cancer genes and polymorphisms of genes related to hormone response, cell protection or DNA repair may increase tumour risk. Proto-oncogenes such as myc, EIF3S3, bcl2 or growth factor encoding genes have been found to play a role during tumour development. TP53 and PTEN are among tumor suppressor genes inactivated in PCA. The activity of PCA relevant genes may be modified by DNA methylation or histone acetylation and signalling pathways (such as Wnt signalling) have been found to be deregulated. Alterations affecting the proteasome pathway may modify the degradation of proteins involved in growth or apoptosis. A major importance has finally been attributed to epithelial stromal interactions in PCA development and progression.

A characteristic feature of PCA is heterogeneity with respect to clinical behaviour and outcome. The frequently low malignant incidental carcinomas of the transitional zone may be other entities than the mostly manifest tumours of the peripheral zone. Heterogeneity of clinical behaviour and outcome also exists between individual tumors of incidental and manifest PCA groups. An androgen-independent recurrence after androgen depletion cannot be predicted in spite of some known molecular mechanisms of androgen independence (such as silencing of the androgen receptor gene by promotor hypermethylation or androgen-independent receptor-activation). Evaluation of prognosis has direct impacts for treatment reaching from „watchful waiting“ to radical surgery combined to adjuvant antihormonal and cytostatic therapy.

Joint efforts are particularly promising for major progress of research about etiology and outcome of incidental and manifest PCA. A series of common cases should be analysed systematically in a pluridisciplinary approach by standardized methods (SOPs) in order to better understand molecular differences between the normal prostate zones (prone to either incidental or manifest tumors) and between individual cancers. Lasermicrodissection provides the tools for separate analyses of precancerous lesions as well as epithelial and stromal cells.