CONSTITUTIONAL MUTATION IN EXON-8 OF THE P53 GENE IN A PATIENT WITH MULTIPLE PRIMARY TUMORS - MOLECULAR AND IMMUNOHISTOCHEMICAL FINDINGS

We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benig n and malignant tumours (tricholemmoma of the scalp, multiple trichoep itheliomata of the face, osteosarcoma of the ovary, bilateral breast c ancer, maligant fibrous histiocytoma of the thigh and endometrial aden ocarcinoma) and belongs to a family with some, but not all, features o f the Li-Fraumeni syndrome. The mutation, found in both blood lymphocy te and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early a ge. We have demonstrated that formalin-preserved material from these t umours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunoh istochemical positivity with four antibodies to the p53 protein. Posit ive staining was also seen in scattered nuclei of morphologically norm al epidermal keratinocytes and pilosebaceous cells, but not in lymphoc ytes or other morphologically normal cells from the index case. Howeve r, a similar staining pattern in apparently normal tissue was also obs erved in 13/48 sections from other individuals with various skin condi tions (melanocytic naevi, psoriasis and normal skin adjacent to malign ant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p 53 mutations.