Expression profiling using tissue microarray in 211 malignant fibrous histiocytomas confirms the prognostic value of Ki-67.
The tissue microarray technology is a high-throughput technique that allows studies of multiple markers in large tumor materials. We performed immunohistochemical profiling using tissue microarray and immunostaining for Ki-67, p53, bcl-2, CD44, cyclin A and Pgp in a series of 211 malignant fibrous histiocytomas (MFHs) with correlation to prognosis. Tissue from 50 local recurrences and 20 metastases was available for comparison with the primary tumors. In univariate analysis, Ki-67 was the only immunohistochemical marker significantly correlated with metastasis with a hazard ratio of 1.9. Multivariate analysis, with tumor size, depth, necrosis, vascular invasion, mitotic rate and Ki-67 expression, revealed an independent prognostic value of tumor size and Ki-67. Local recurrences did not differ from the corresponding primary tumors, whereas metastases showed a trend for upregulation of cyclin A and Pgp. In this large series of MFHs, a tumor size greater than 8 cm and a Ki-67 index of more than 20% were strong and independent prognostic factors for metastasis. In contrast, p53, bcl-2, CD44, cyclin A and Pgp, which have previously been suggested as prognostic factors in soft tissue sarcomas, did not show such correlations. Hence, we suggest that proliferation, as measured by Ki-67 index, should be considered as a prognostic marker in clinical management of pleomorphic soft tissue sarcomas.
Department of Oncology, Jubileum Institution, Lund University, 22185 Lund, Sweden. Jacob.Engellau@onk.lu.se
Jacob
J
Engellau
Annette
A
Persson
Pär-Ola
PO
Bendahl
Måns
M
Akerman
Henryk A
HA
Domanski
Bodil
B
Bjerkehagen
Peer
P
Lilleng
Johan
J
Weide
Anders
A
Rydholm
Thor A
TA
Alvegård
Mef
M
Nilbert
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019925:Cyclin A / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018219:Histiocytoma, Benign Fibrous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D019925:Cyclin A; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53