Prognostic value of proliferation in pleomorphic soft tissue sarcomas: a new look at an old measure.
Though proliferation has repeatedly shown a prognostic role in sarcomas, it has not reached clinical application. We performed a comprehensive evaluation of the prognostic role of 5 proliferation measures in a large series of soft tissue sarcomas of the extremities and the trunk wall. One hundred ninety-six primary soft tissue sarcomas of the extremities and the trunk wall were subjected to DNA flow cytometry for quantification of S-phase fraction and to immunohistochemical evaluation of Ki-67, Top2a, p21, and p27Kip1. In univariate analysis, positive expression of Ki-67 (hazard ratio = 4.5, CI = 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy.
Department of Oncology, Institute of Clinical Sciences, Lund, Skåne University Hospital, Lund University, Lund, Sweden.
Jojanneke M
JM
Seinen
Mats
M
Jönsson
Pär-Ola O
PO
Bendahl
Bo
B
Baldetorp
Eva
E
Rambech
Måns
M
Åkerman
Anders
A
Rydholm
Mef
M
Nilbert
Ana
A
Carneiro
D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000473:pathology*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human