Prognostic implication of the p53 protein and Ki-67 antigen immunohistochemistry in malignant fibrous histiocytoma.

Abstract

Mounting evidence indicates that p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an unfavorable prognosis for patients with some types of carcinoma. The prognostic significance of p53 overexpression in malignant fibrous histiocytomas (MFHs) of soft tissue has not yet been elucidated. Expressions of p53 protein and Ki-67 antigen in 54 primary MFHs of soft tissue were investigated immunohistochemically and indexed quantitatively by counting the number of immunoreactive nuclei versus the total neoplastic nuclei in the representative fields of each tumor to evaluate their prognostic implications and interrelations with other clinicopathologic parameters. The percentages (labeling indices [LIs]) of p53 and Ki-67-immunoreactive nuclei versus the total neoplastic nuclei were 0.1-93.2% (mean +/- standard deviation [SD], 40.6% +/- 21.8%) and 5.3-90.8% (mean +/- SD, 42.7% +/- 29.4%), respectively. The Ki-67 LI correlated with histologic grade (P = 0.01498), primary tumor size (P = 0.04985), disease free interval (reverse correlation, P = 0.00776), and recurrence and metastasis (P = 0.00360). The p53 LI correlated with primary tumor size (P = 0.00431) but did not show any significant correlation with histologic grade, Ki-67 LI, primary tumor size, disease free interval, or recurrence and metastasis. Other significant correlations included histologic grade and disease free interval (P = 0.00010), primary tumor size and disease free interval (reverse correlation, P = 0.00869), histologic grade and recurrence (P = 0.02714), and primary tumor size and primary tumor location (P = 0.00028). In the grouped survival analysis, patients with recurrence or metastasis or with tumors of larger size (> or = 7 cm), high histologic grade, or higher Ki-67 LI (> or = 25%) had a significantly reduced survival (P < 0.05). The different p53 immunohistochemical expression and the different histologic types did not reflect different cumulative survival (P > 0.05). Regression analysis revealed that the primary tumor size and histologic grade, but not Ki-67 or p53 LIs, were independent statistical variables for prognostication. These results indicate that (1) primary tumor size and histologic grade are two important prognostic factors, (2) Ki-67 LI should be used in adjunct with other main prognostic factors for patients with MFHs, and (3) nuclear p53 overexpression in MFHs of soft tissue is a comparatively common event that has no prognostic implication.