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Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria.

Authors :
Huang HY
Huang WW
Lin CN
Eng HL
Li SH
Li CF
Lu D
Yu SC
Hsiung CY
Source :
Annals of surgical oncology [Ann Surg Oncol] 2006 Dec; Vol. 13 (12), pp. 1633-44. Date of Electronic Publication: 2006 Sep 30.
Publication Year :
2006

Abstract

Background: Inactivation of p16(INK4A) promotes G1/S progression of cell cycle. Minichromosome maintenance protein-2 (Mcm2), a novel cell proliferation marker, is known to better correlate with clinical outcomes than Ki-67 in many carcinomas. Since gastrointestinal stromal tumors (GISTs) sometimes remains challenging in prognostication, we analyzed the utility of these three markers in GISTs.<br />Methods: Immunohistochemistry was performed in tissue microarrays of 277 primary GISTs and correlated with NIH consensus criteria and clinical outcomes.<br />Results: The increment of NIH risk levels significantly correlated with increasing labeling indices (LI) of both Ki-67 (P <.001) and Mcm2 (P <.001) and loss of p16(INK4A) expression (P <.035). However, the latter aberration did occur in 23% of very low/low-risk GISTs. The relationship between Mcm2 and Ki-67 LIs could be modeled as linear (P <.001, r = 0.697), while Mcm2 LI was considerably higher (P <.001) with a stepwise escalation related to risk levels. Ki-67 LI >5% (P <.0001) and Mcm2 LI >10% (P <.0001) were strongly predictive of inferior disease-specific survival (DSS), while aberrant loss of p16(INK4A) only reached a trend (P = .0954). In multivariate analyses, independent adverse factors of DSS were high-risk category (RR = 16.93, P <.0001), metastatic disease (RR = 4.12, P = .0015), Ki-67 LI >5% (RR = 3.55, P = .001), and presence of epithelioid histology (RR = 2.17, P = .0308).<br />Conclusions: Prognostic efficacy of NIH consensus criteria is substantiated. P16(INK4A) deregulation can occur early in GIST tumorigenesis and marginally correlates with patient survival. Despite Ki-67 LI being an independent prognosticator, simultaneous detection of Mcm2 is recommended as a prognostic adjunct of GISTs, given its better sensitivity and stepwise escalation with increasing risk levels.

Details

Language :
English
ISSN :
1068-9265
Volume :
13
Issue :
12
Database :
MEDLINE
Journal :
Annals of surgical oncology
Publication Type :
Academic Journal
Accession number :
17013685
Full Text :
https://doi.org/10.1245/s10434-006-9188-4