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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 APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 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
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
leiomyosarcoma, soft tissue sarcoma, Ki-67, proliferation, variability, intratumor
in
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
volume
115
issue
6
pages
707 - 712
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000246910700003
  • scopus:34249810648
ISSN
1600-0463
DOI
10.1111/j.1600-0463.2007.apm_650.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Pathology, (Lund) (013030000), Department of Orthopaedics (Lund) (013028000)
id
cdd0ab7e-c2f0-4e81-8800-c89531690930 (old id 651202)
date added to LUP
2016-04-01 11:45:28
date last changed
2022-02-25 20:51:42
@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}},
  keywords     = {{leiomyosarcoma; soft tissue sarcoma; Ki-67; proliferation; variability; intratumor}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{707--712}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}},
  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}},
  doi          = {{10.1111/j.1600-0463.2007.apm_650.x}},
  volume       = {{115}},
  year         = {{2007}},
}