Ki-67 detected by MIB-1 predicts distant metastasis and tumor mortality in primary, high grade extremity soft tissue sarcoma Journal Article

  

Authors:	Heslin, M. J.; Cordon-Cardo, C.; Lewis, J. J.; Woodruff, J. M.; Brennan, M. F.
Article Title:	Ki-67 detected by MIB-1 predicts distant metastasis and tumor mortality in primary, high grade extremity soft tissue sarcoma
Abstract:	BACKGROUND. Preoperative staging of localized extremely soft tissue sarcoma (STS) includes tumor grade, size, and depth. A positive microscopic margin (PMM) adds prognostic information postoperatively, which is not helpful for preoperative stratification into low and high risk groups. This study was undertaken to identify molecular markers associated with poor outcome that could be used to refine the preoperative staging of high grade extremity STS. METHODS. Between January 1, 1983, and December 31, 1989, 1416 patients were entered into the STS prospective data base at the Memorial Sloan-Kettering Cancer Center. Of 232 patients identified with primary, high grade extremity lesions, 121 had tissue available for immunohistochemical (IHC) analysis. The clinicopathologic variables and molecular markers for the original 232 patients were correlated with those for the 121 patients analyzed in the current study. Overexpression of Ki-67, p53, and mdm2 and deletion of Rb were determined via standard IHC techniques on serial paraffin sections. Categoric overexpression was defined as ≤20% nuclear staining. Continuous determination of the percentage of nuclear staining was also used for correlation with distant metastasis (DM) and tumor mortality (TM). Univariate and multivariate analyses were conducted with log rank and Wilcoxon tests and Cox regression analyses, respectively. RESULTS. The median follow-up was 64 months. Fifty-four of the 121 patients (45%) developed DM. Fifty-one of the 121 patients (42%) died of their disease. Factors found to be significant in univariate and multivariate analyses for both DM and TM were Ki-67 score, size, and PMM (all P values <0.05). Five year freedom from DM with a Ki-67 score of <20 was 70% versus 50% for a score. Overexpression of p53 of mdm2 or deletion of Rb did not correlate with increased risk of DM or TM alone or in combination with a Ki-67 score of ≤20. CONCLUSIONS. In addition to standard preoperative criteria, Ki-67 score is an independent prognostic molecular marker that predicts DM and TM in high grade extremity STS. Selecting patients with high grade tumors for preoperative investigational treatment may be further refined according to whether the patients have Ki-67 score of ≤20 and large tumor size.
Keywords:	adult; controlled study; human tissue; aged; middle aged; gene mutation; major clinical study; cancer grading; preoperative evaluation; ki 67 antigen; ki-67 antigen; cell cycle; metastasis; neoplasm recurrence, local; protein p53; prediction; cancer mortality; sarcoma; tumor suppressor gene; antibodies, monoclonal; ki-67; limb tumor; soft tissue sarcoma; extremities; immunophenotyping; retinoblastoma protein; p53; mdm2; mib-1; rb; genes, retinoblastoma; humans; human; male; female; priority journal; article; monoclonal antibody ki 67; preoperarive evaluation
Journal Title:	Cancer
Volume:	83
Issue:	3
ISSN:	0008-543X
Publisher:	Wiley Blackwell
Date Published:	1998-08-01
Start Page:	490
End Page:	497
Language:	English
DOI:	10.1002/(sici)1097-0142(19980801)83:3<490::aid-cncr18>3.0.co;2-r
PUBMED:	9690542
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032147112&doi=10.1002%2f%28SICI%291097-0142%2819980801%2983%3a3%3c490%3a%3aAID-CNCR18%3e3.0.CO%3b2-R&partnerID=40&md5=70752d2318936a2509b8464f863e9888
Notes:	Article -- Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology that took place March 20 –23, 1997 in Chicago, IL -- Export Date: 12 December 2016 -- Source: Scopus

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