Prognostic impact of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas.
OBJECTIVE
The purpose of this study is to clarify the prognostic significance of expression of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas (STS). Optimised treatment of STS requires better identification of high risk patients who will benefit from adjuvant therapy. The prognostic significance of Jab1, p16, p21, p62, Ki67 and Skp2 in STS has not been sufficiently investigated.


METHODS
Tissue microarrays from 193 STS patients were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of Jab1, p16, p21, p62, Ki67 and Skp2.


RESULTS
In univariate analyses, high tumor expression of Ki67 (P = 0.007) and Skp2 (P = 0.050) correlated with shorter disease-specific survival (DSS). In subgroup analysis, a correlation between Skp2 and DSS was seen in patients with malignancy grade 1 or 2 (P = 0.027), tumor size >5 cm (P = 0.018), no radiotherapy given (P = 0.029) and no chemotherapy given (P = 0.017). No such relationship was apparent for Jab1, p16, p21 and p62; but p62 showed a positive correlation to malignancy grade (P = 0.019). Ki67 was strongly positively correlated to malignancy grade (P = 0.001). In multivariate analyses, Skp2 was an independent negative prognostic factor for DSS in women (P = 0.009) and in patients without administered chemotherapy or radiotherapy (P = 0.026).


CONCLUSIONS
Increased expression of Skp2 in patients with soft tissue sarcomas is an independent negative prognostic factor for disease-specific survival in women and in patients not administered chemotherapy or radiotherapy. Besides, further studies are warranted to explore if adjuvant chemotherapy or radiotherapy improve the poor prognosis of STS with high Skp2 expression.
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. sveinung.sorbye@unn.no
Sveinung W
SW
Sorbye
Thomas K
TK
Kilvaer
Andrej
A
Valkov
Tom
T
Donnem
Eivind
E
Smeland
Khalid
K
Al-Shibli
Roy M
RM
Bremnes
Lill-Tove
LT
Busund
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis / Q000378:metabolism; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000071456:Sequestosome-1 Protein; D046888:Tissue Array Analysis; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D044786:S-Phase Kinase-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex