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

Fernebro, Josefin LU ; Engellau, Jacob LU ; Persson, Annette LU ; Rydholm, Anders LU and Nilbert, Mef LU (2007) In Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS) 115(6). p.707-712
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... (More)
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-1 alpha 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
leiomyosarcoma, soft tissue sarcoma, Ki-67, proliferation, variability, intratumor
in
Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS)
volume
115
issue
6
pages
707 - 712
publisher
John Wiley & Sons
external identifiers
  • wos:000246910700003
  • scopus:34249810648
ISSN
1600-0463
DOI
10.1111/j.1600-0463.2007.apm_650.x
language
English
LU publication?
yes
id
cdd0ab7e-c2f0-4e81-8800-c89531690930 (old id 651202)
date added to LUP
2007-12-11 09:37:02
date last changed
2017-01-01 04:30:47
@article{cdd0ab7e-c2f0-4e81-8800-c89531690930,
  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-1 alpha 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.},
  author       = {Fernebro, Josefin and Engellau, Jacob and Persson, Annette and Rydholm, Anders and Nilbert, Mef},
  issn         = {1600-0463},
  keyword      = {leiomyosarcoma,soft tissue sarcoma,Ki-67,proliferation,variability,intratumor},
  language     = {eng},
  number       = {6},
  pages        = {707--712},
  publisher    = {John Wiley & Sons},
  series       = {Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS)},
  title        = {Standardizing evaluation of sarcoma proliferation - higher Ki-67 expression in the tumor periphery than the center},
  url          = {http://dx.doi.org/10.1111/j.1600-0463.2007.apm_650.x},
  volume       = {115},
  year         = {2007},
}