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Standardizing evaluation of sarcoma proliferation— higher Ki‐67 expression in the tumor periphery than the center
Author(s) -
FERNEBRO JOSEFIN,
ENGELLAU JACOB,
PERSSON ANNETTE,
RYDHOLM ANDERS,
NILBERT MEF
Publication year - 2007
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2007.apm_650.x
Subject(s) - ki 67 , immunostaining , staining , pathology , immunohistochemistry , tissue microarray , sarcoma , proliferation marker , biology , medicine
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.