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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2006

01-12-2006

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: Hsuan-Ying Huang, MD, Wen-Wei Huang, MD, Ching-Nan Lin, MD, Hock-Liew Eng, MD, Shau-Hsuan Li, MD, Chien-Feng Li, MD, David Lu, MD, Shih-Chen Yu, BS, Ching-Yeh Hsiung, MD

Published in: Annals of Surgical Oncology | Issue 12/2006

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Abstract

Background

Inactivation of p16INK4A 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.

Methods

Immunohistochemistry was performed in tissue microarrays of 277 primary GISTs and correlated with NIH consensus criteria and clinical outcomes.

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 p16INK4A 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 p16INK4A 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).

Conclusions

Prognostic efficacy of NIH consensus criteria is substantiated. P16INK4A 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.
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Metadata
Title
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
Hsuan-Ying Huang, MD
Wen-Wei Huang, MD
Ching-Nan Lin, MD
Hock-Liew Eng, MD
Shau-Hsuan Li, MD
Chien-Feng Li, MD
David Lu, MD
Shih-Chen Yu, BS
Ching-Yeh Hsiung, MD
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9188-4

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