Malignant peripheral nerve sheath tumours: high Ki67 labelling index is the significant prognostic indicator.
OBJECTIVE
We investigated p53, Ki67, MDM2, and p21WAF1/CIP1 in order to evaluate its relationship with prognosis in malignant peripheral nerve sheath tumours (MPNST).


RESULTS
In 49 cases of MPNSTs, the immunohistochemical studies of Ki67, p53, MDM2, p21WAF1/CIP1 and polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with direct sequencing of p53 were performed with the formalin-fixed paraffin-embedded tissue. In 43 cases with survival data available, an evaluation of the prognostic significance of clinicopathological factors was also carried out. A high Ki67 labelling index (LI) (>25%) was correlated with a reduced survival rate in the 43 cases of MPNST (P=0.0106, log-rank test). Furthermore, there was a significant correlation between the Ki67 LI and the immunohistochemical expression of p53 or MDM2. In 17 MPNST cases, PCR amplification of exons 5 through 8 of the p53 gene was successful. One case showed a base change of codon 240 (AGT-->AGC), but translated amino acid (Ser) remained unchanged. Multivariate Cox analysis of our series showed that the association of von Recklinghausen's disease, tumour depth, and the presence of rhabdomyoblasts (malignant triton tumour) each had an independent negative impact on overall survival.


CONCLUSIONS
High Ki67 LI (>25%) was of significant prognostic value in MPNST.
Watanabe
T
T
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Oda
Y
Y
Tamiya
S
S
Kinukawa
N
N
Masuda
K
K
Tsuneyoshi
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2