RELATIONSHIP OF P53 GENE ALTERATIONS WITH TUMOR PROGRESSION AND RECURRENCE IN OLFACTORY NEUROBLASTOMA

Olfactory neuroblastoma (ONE) is a rare neuroectodermal tumor whose cl inical course is not effectively predicted by initial stage or grade; p53 tumor suppressor gene alterations have not been determined concern ing the ONE pathobiology and recurrence. We analyzed 18 formalin-fixed , paraffin-embedded ONE specimens (12 primary tumors and six recurrenc es or metastases) from 14 patients for p53 alterations using immunohis tochemistry for p53 and WAF1 together with topographic genotyping (sel ection of minute tissue targets from unstained sections, PCR [polymera se chain reaction] amplification of exons 5-8 followed by direct DNA s equencing). Sequential material representing tumor recurrence or metas tasis was available in four cases to compare genetic alterations over time in the same patient. None of the cases showed strong, diffuse p53 immunostaining. Focal weak to moderate intensity staining was evident in nine of 14 cases. Mutations in p53 were not detected in any of the cases, suggesting hyperexpression of p53 wild-type protein. Hyperexpr ession was further confirmed by correlation of WAF-1 and p53 immunopos itivity. Importantly, in four cases with recurrence or metastasis, tum ors manifested p53 wild-type hyperexpression. It appears that p53 poin t mutation does not play an important role in the initial development of ONE; however, p53 wild-type hyperexpression may occur in subsets of ONE likely to show local aggressive behavior and a tendency for recur rence. Wild-type p53 hyperexpression may be an important event in late r stages of ONE growth and progression.