Prognostic value of Ki‐67 expression in 182 soft tissue sarcomas. Proliferation — a marker of metastasis?

Abstract

Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki‐67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki‐67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty‐two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow‐up time for survivors was 6 years (1–13). We used a semiquantitative score to the assess percentage of Ki‐67‐positive cells: ≥ 10% (n = 86), >10–25% (n = 57), >25–50% (n = 30), >50–75% (n = 7), >75–100% (n = 2). Increasing Ki‐67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S‐phase fraction, and metastasis. A Ki‐67 index Ki‐D 10% (n = 86) and >10% (n = 96) defined two groups who had 84% and 56% 3‐year metastasis‐free survival (p= 0.0001), respectively. Tumours with Ki‐D>10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S‐phase fraction. Ki‐67 expression may be helpful in predicting survival of patients with soft tissue sarcomas.

β-Catenin in Soft tissue Sarcomas: Expression is Related to Proliferative Activity in High-Grade Sarcomas

“…It is being expressed in all active phases of the cycle, not, however, during the G 0-phase, which renders its significance as a marker of proliferation (31,32). The development of the Ki-67-equivalent monoclonal antibody MIB-1 allows the immunohistochemical staining of routinely processed, paraffin-embedded tissue (33).…”

“…This percentage was determined by counting individual fields (medium power, ϫ25): MIB-1 score 1 ϭ less than 10%; 2 ϭ 10 to 25%; 3 ϭ more than 25%. This classification was used according to previous studies about proliferation in sarcomas, which determined the prognostic significance of 10% or more positive MIB-1 results (31,34). So-called "hot-spot" areas consisting of nodular concentrations of MIB-1 positive cell nuclei were not considered, unless clearly more than three were found within the same field (31).…”

“…This classification was used according to previous studies about proliferation in sarcomas, which determined the prognostic significance of 10% or more positive MIB-1 results (31,34). So-called "hot-spot" areas consisting of nodular concentrations of MIB-1 positive cell nuclei were not considered, unless clearly more than three were found within the same field (31). A total of three different fields were evaluated, which were determined by systematic movement of predetermined distances of the slides.…”

Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance analysed in 160 patients

“…P-value for highrisk group = 0.1 DISCUSSION S-phase fraction (SPF) has been identified as a prognostic factor in several malignancies, breast cancer, non-small-cell lung cancer, colorectal cancer and carcinoma of the ovary (for review, see Merkel and McGuire, 1990). In soft-tissue sarcoma, several markers of proliferation have yielded prognostic information (Ueda et al, 1989;Stenfert Kroese et al, 1990;Becker et al, 1991;Alho et al, 1993;Oda et al, 1993;Choong et al, 1994;Dreinhofer et al, 1994;Drobnjak et al, 1994), but SPF has not been thoroughly tested together with other strong clinicopathological factors in a multivariate analysis. In 100 of 260 samples, SPF could not be calculated, a fact that restricts the usefulness of the method.…”

“…Proliferating cell nuclear antigen (PCNA) and Ki-67 have been associated with poor prognosis (Ueda et al, 1989;Stenfert Kroese et al, 1990; Oda et al, 1993;Choong et al, 1994;Dreinhofer et al, 1994;Drobnjak et al, 1994), whereas others have failed to show this (Herzberg et al, 1992). Moreover, a high fraction of cells in S-or S+G2-phase, as determined by flow cytometry, has been shown to be prognostic (Becker et al, 1991;Alho et al, 1993) and has also been used to identify patients with short-term response to chemotherapy (Schmidt et al, 1993).…”