ABSTRACT
From a biological point of view, two remarkable characteristics attract attention to unknown primary tumors (UPTs): (i) an atypical distribution of the tumor mass between the metastatic and primary lesions, suggesting a relative or absolute inhibition of primary tumor growth and; (ii) a peculiar pattern of metastatic spread with early involvement of multiple organs and rapid progression. Deletions or rearrangements of chromosome 1p and c-myc overexpression are consistently found in UPTs as in other aggressive malignancies. Some other characteristics are more intriguing such as the overexpression of Bcl-2, which is frequent in low grade malignancies but is also frequent in UPTs. There is evidence that p53 is rarely mutated in UPTs. If this is confirmed, this observation could be pivotal in future
investigations on the acquisition of the UPT metastatic phenotype. The mechanisms of primary tumor growth inhibition remain completely hypothetical; immune and inflammatory mechanisms might play a role in the inhibition or regression of the primary tumor. New insights on UPT biology will come from high-throughput genome, transcriptome, and proteome analyses. It will be important to combine data on gene expression with data on structural gene alterations. Investigations of p53 and related proteins (p73, Arf, MDM2 etc.) as well as of the Bcl-2 family are among the priorities for a better understanding of the etiology of UPTs.
