Mutations of the p53 tumor suppressor gene are the single most common genetic alterations in human cancers. Recently, a distinct nucleotide substitution was identified in exon 10 of the p53 gene, leading to an Arg337His mutation in 97% of children with adrenocortical tumors from Southern Brazil. In the present study, we investigated the presence of this mutation in a larger series of 55 patients (37 adults and 18 children) with benign and malignant sporadic adrenocortical tumors. None of the patients had family cancer histories that conformed to the criteria for Li-Fraumeni syndrome. Twenty-one asymptomatic close relatives of patients with p53 mutations and 60 normal unrelated individuals were also studied. The missense Arg337His mutation was identified in 19 patients (14 children and 5 adults), and 8 of 11 cases studied had LOH. Among the 19 patients with the Arg337His mutation, only one boy and three adults showed fatal evolution or recurrent metastases. This mutation was also identified in heterozygous state in asymptomatic first-degree relatives of the patients, indicating that Arg337His mutation was inherited in most cases. In contrast, this mutation was not found in 120 alleles of normal unrelated controls. In conclusion, the germ line Arg337His mutation of p53 protein is present at a high frequency (77.7%) in children with benign or malignant sporadic adrenocortical tumors, but it is not restricted to the pediatric group, since 13.5% of adults with adrenocortical tumors also had this mutation. The presence of this mutation was related to unfavorable prognosis in most of the adults, but not in the children with adrenocortical tumors.

OBJECTIVE: To investigate the biological behavior of classical and atypical osteoblastomas in comparison to osteosarcomas. METHODS: Based on histological parameters, 30 osteoblastomas were subclassified as classical osteoblastomas (23/30) or atypical osteoblastoma (high cellularity, prominent blue osteoid, and epithelioid osteoblasts-7/30). Comparative immunohistochemical and clinical analysis was performed in 17 cases of patients with high-grade osteosarcoma. Formalin-fixed, paraffin-embedded archival tissue was immunostained for p53 and proliferation cell nuclear antigen. Tumors with positive p53 stain underwent molecular analyses for fragments of exon 10. RESULTS: The mean proliferating cell nuclear antigen indexes for classical osteoblastoma, atypical osteoblastoma, and osteosarcoma were 33%, 61%, and 79%, respectively. The atypical subgroup showed similar results to those of the osteosarcoma group (P < 0.001). p53 protein was detected in 4 (13%) osteoblastomas (3 of these were atypical osteoblastoma), and 4 osteosarcomas (23%) also showed p53 positivity. DNA mutation performed in p53-positive cases was confirmed in exon 10 in 2 atypical osteoblastomas (2/3), 1 classical osteoblastoma (1/1), and 1 osteosarcoma (1/4). Disease recurrence was correlated with p53 expression (P = 0.009), atypical subtype (P = 0.031), spiculated blue bone on histology (P = 0.018), and proliferating cell nuclear antigen labeling index ≥ 40 (P = 0.015). CONCLUSION: These results validate atypical osteoblastoma as an entity, with p53 and proliferation cell nuclear antigen immunoexpression closer to that of osteosarcoma than of classical osteoblastoma. Proliferating cell nuclear antigen labeling index and p53 may be useful predictors of recurrence.

PURPOSE:The differential diagnosis between benign and malignant adrenal cortical tumors circumscribed to the gland is controversial. One hundred and seven patients with adrenal cortex tumors (excluding those with primary hyperaldosteronism) were studied to assess the 5-year survival rate of adults, children, patients stratified by pathological stage, and patients stratified according to Weiss's score of <3 or >3.METHODS: The patients were evaluated both clinically and biochemically. One hundred and five patients underwent surgery and were classified pathologically as stages I, II, III, or IV. The tumors were weighed, measured, and classified according to Weiss's criteria and divided into 2 groups: <3 and >3.RESULTS: After 5 years, the survival rate was 77.5% for the whole group, 74.61% for the adults, 84.3% for the children, 100% for stage I, 83.9% for stage II, 33% for stage III, and 11.7% for stage IV groups. Additionally, after 5 years, 100% of the patients with tumors with Weiss's score <3 were alive compared to 61.65% of those with Weiss's score >3. The average weights of the tumors of score <3 and >3 were 23.38 g + 41.36 g and 376.3 + 538.76 g, respectively, which is a statistically significant difference. The average sizes of tumors of Weiss's score <3 and >3 were 3.67 + 2.2 cm and 9.64 + 5.8 cm, respectively, which is also a statistically significant difference.CONCLUSIONS: Weiss's score may be a good prognostic factor for tumors of the adrenal cortex. Additionally, there was a statistically significant difference between the average weight and size of tumors with benign behavior (Weiss's score <3) and those with malignant behavior (Weiss's score >3).

When diagnosed in children, adrenal carcinoma is associated with virilism and a less aggressive natural history; however, when it occurs in adults, the disease presents more commonly as a mixed Cushing-virilizing syndrome and has a virulent course. The Weiss histologic criteria appear to correlate best with disease prognosis, but other histochemical, cell cycle, and genetic markers have not, to date, aided in disease management.