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Standardizing evaluation of sarcoma proliferation— higher Ki-67 expression in the tumor periphery than the center

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Fernebro J, Engellau J, Persson A, Rydholm A, Nilbert M. Standardizing evaluation of sarcoma proliferation—higher Ki-67 expression in the tumor periphery than the center. APMIS 2007;115:707–12.

Soft tissue sarcomas often present as large and histopathologically heterogenous tumors. Proliferation has repeatedly been identified as a prognostic factor and immunostaining for Ki-67 represents the most commonly used proliferation marker. There is, however, a lack of consensus on how to evaluate Ki-67 staining regarding optimal cut-off levels, selection of tumor areas, and the number of tumor cells to evaluate. We assessed the impact of targeting peripheral versus central tumor areas using tissue microarray-based staining for Ki-67 throughout the tumor diameter in 25 leiomyosarcomas. In 18/25 tumors, Ki-67 expression was higher in the tumor periphery. If 10% staining tumor nuclei was used as cut-off and the maximal Ki-67 staining section in the tumor periphery was considered, 21/25 tumors would have been classified as highly proliferative compared to 14/25 if the tumor center had been analyzed. Similar results were obtained also when higher cut-off levels were used and if the mean expression rather than the maximal expression was considered and the differences were neither caused by necrosis nor by hypoxia (assessed as HIF-1α expression). Our findings suggest that the determination of proliferation in soft tissue sarcomas should be standardized for clinical application of Ki-67 as a prognostic marker.

Keywords: Ki-67; Soft tissue sarcoma; intratumor variability; leiomyosarcoma; proliferation

Document Type: Research Article


Affiliations: 1: Departments of Oncology, 2: Pathology, and 3: Orthopedics, Institute of Clinical Sciences, Lund University Hospital, Lund, Sweden

Publication date: June 1, 2007

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