PROGNOSTIC IMPLICATION OF THE P53 PROTEIN AND KI-67 ANTIGEN IMMUNOHISTOCHEMISTRY IN MALIGNANT FIBROUS HISTIOCYTOMA

Background. Mounting evidence indicates that p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an un favorable prognosis for patients with some types of carcinoma. The pro gnostic significance of p53 overexpression in malignant fibrous histio cytomas (MFHs) of soft tissue has not yet been elucidated. Methods. Ex pressions of p53 protein and Ki-67 antigen in 54 primary MFHs of soft tissue were investigated immunohistochemically and indexed quantitativ ely by counting the number of immunoreactive nuclei versus the total n eoplastic nuclei in the representative fields of each tumor to evaluat e their prognostic implications and interrelations with other clinicop athologic parameters. Results. The percentages (labeling indices [LIs] ) of p53 and Ki-67-immunoreactive nuclei versus the total neoplastic n uclei 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 si ze (P = 0.04985), disease free interval (reverse correlation, P = 0.00 776), and recurrence and metastasis (P = 0.00360). The p53 LI correlat ed with primary tumor size (P = 0.00431) but did not show any signific ant correlation with histologic grade, Ki-67 LI, primary tumor size, d isease 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 correl ation, P = 0.00869), histologic grade and recurrence (P = 0.02714), an d primary tumor size and primary tumor location (P = 0.00028). In the grouped survival analysis, patients with recurrence or metastasis or w ith tumors of larger size (greater than or equal to 7 cm), high histol ogic grade, or higher Ki-67 LI (greater than or equal to 25%) had a si gnificantly reduced survival (P < 0.05). The different p53 immunohisto chemical expression and the different histologic types did not reflect different cumulative survival (P > 0.05). Regression analysis reveale d that the primary tumor size and histologic grade, but not Ki-67 or p 53 LIs, were independent statistical variables for prognostication. Co nclusions. These results indicate that (1) primary tumor size and hist ologic grade are two important prognostic factors, (2) Ki-67 LI should be used in adjunct with other main prognostic factors for patients wi th MFHs, and (3) nuclear p53 overexpression in MFHs of soft tissue is a comparatively common event that has no prognostic implication.