title: Standardizing evaluation of sarcoma proliferation- higher Ki-67 expression in the tumor periphery than the center.
abstract: 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-1alpha 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.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Lund University Hospital, Lund, Sweden. Josefin.Fernebro@med.lu.se
authors.forename: Josefin
authors.initials: J
authors.lastname: Fernebro
authors.forename: Jacob
authors.initials: J
authors.lastname: Engellau
authors.forename: Annette
authors.initials: A
authors.lastname: Persson
authors.forename: Anders
authors.initials: A
authors.lastname: Rydholm
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010338:Pathology, Clinical / Q000379:methods / Q000592:standards; D012015:Reference Standards; D012509:Sarcoma / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen