Proliferation and apoptosis of tumour cells before and after neoadjuvant therapy for high-grade extremity sarcomas: divergent associations with tumour response and prognosis.
OBJECTIVE
To evaluate proliferation and apoptosis in high-grade sarcomas of the extremities before and after preoperative radio-hyperthermo-chemotherapy (RHC) and to determine the relationship between these parameters and treatment outcomes.


RESULTS
Pre- and post-RHC specimens of 41 soft tissue and bone tumours were immunohistochemically stained for minichromosome maintenance protein (MCM) 2 and caspase 3 as proliferation and apoptosis markers, respectively, based on a preliminary study comparing them with conventional markers. Indices were calculated as a percentage of positive cells by counting tumour cells in the most frequently labelled areas. MCM2, caspase 3 and MCM2/caspase 3 (growth) indices were 45.3 +/- 21.9%, 4.1 +/- 7.1% and 82.9 +/- 104.5, respectively, in pre-RHC specimens and 35.4 +/- 30.8%, 39.2 +/- 34.6% and 5.3 +/- 11.7, respectively, in post-RHC specimens. Response scores showed positive correlation with pre-RHC MCM2 and post-RHC caspase 3 indices, inverse correlation with post-RHC MCM2 and post-RHC growth indices and no correlation with prognosis. Multivariate analysis revealed high pre-RHC MCM2 and high post-RHC growth indices as significant unfavourable prognostic factors.


CONCLUSIONS
High proliferative activity in untreated sarcoma may predict good response to neoadjuvant therapy, but poor prognosis, whereas a high growth index, i.e. high proliferation:apoptosis ratio in a post-neoadjuvant therapy tumour specimen may indicate poor response and poor prognosis.
Matsubara
T
T
Department of Pathology, Nagoya City University School of Medicine, Nagoya, Japan.
Eimoto
T
T
Okabe
M
M
Miyabe
S
S
Fujiyoshi
Y
Y
Matsushita
Y
Y
Mizutani
J
J
Yamada
S
S
Otsuka
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018213:Neoplasms, Bone Tissue / Q000628:therapy*; D011379:Prognosis; D012509:Sarcoma / Q000628:therapy*