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. 2012 Apr 14;18(14):1664-71.
doi: 10.3748/wjg.v18.i14.1664.

Prognostic significance of PTEN, Ki-67 and CD44s expression patterns in gastrointestinal stromal tumors

Yu-Mei Liang  1 , Xiang-Hong Li, Wen-Mei Li, You-Yong Lu
Affiliations

Prognostic significance of PTEN, Ki-67 and CD44s expression patterns in gastrointestinal stromal tumors

Yu-Mei Liang et al. World J Gastroenterol. .

Abstract

Aim: To develop a prognostic approach for gastrointestinal stromal tumors (GISTs) using a cluster of indicators and follow-up information.

Methods: One hundred and four GISTs that had not been subjected to targeted therapies were collected and classified by NIH risk assessment and anatomic location. By immunohistochemistry, the expressions of PTEN, Ki-67, CD44s matrix metalloproteinase (MMP)-9 and TIMP-1 were detected on tissue microarray. Univariate and multimarker survival analyses were performed and then a COX hazard proportion model was constructed to evaluate a cluster of predictors of GIST.

Results: Our data showed small intestinal GIST are more aggressive than gastric GIST. The NIH risk assessment correlated with disease-free survival for either gastric GIST or small intestinal GIST. Immunohistochemical analysis revealed that Ki-67 labeling indexes (LIs) < 5% predicted higher disease-specific survival (DSS) in gastric and small intestinal GIST. CD44s positivity and PTEN LIs ≥ 50% correlated with higher DSS in gastric GIST. MMP-9 and TIMP-1 had no correlation with survival. Multimarker analysis revealed that the expression pattern of PTEN LIs ≥ 50% combined with Ki-67 LIs < 5% and CD44s positivity reliably predicted favorable outcomes for gastric GIST (P = 0.009), as did the combination of PTEN LIs ≥ 50% and Ki-67 LIs < 5% for small intestinal GIST (P = 0.011). Authors also found that high NIH risk grade was correlated with DSS in patients with gastric GIST and disease-free survival in patients with small intestinal GIST.

Conclusion: PTEN LIs ≥ 50%, Ki-67 LIs < 5% and CD44s positivity provides an accurate, favorable prognosis for gastric GIST. PTEN LIs ≥ 50% and Ki-67 LIs < 5% does the same for small intestinal GIST. Ki-67 LIs enhances the NIH assessment.

Keywords: CD44s; Gastrointestinal stromal tumor; Ki-67; PTEN; Prognosis.

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Figures

Figure 1
Figure 1
Examples of the selected markers expressed in gastrointestinal stromal tumor. A: The tumor cells were strongly positive for CD117 with diffuse membrane staining; B: Nuclear positivity of Ki-67 in the tumor cells; C: Nuclear positivity of PTEN in gastrointestinal stromal tumor; D: CD44s was diffusely positive in tumor cell membrane; E: Matrix metalloproteinase 9 was diffusely positive in cytoplasm; F: TIMP-1 was diffusely positive in cytoplasm. Immunostains counterstained with hematoxylin-eosin, original magnifications × 200.
Figure 2
Figure 2
Kaplan-Meier cumulative survival plots of patients with gastric gastrointestinal stromal tumor. The end point was death due to gastrointestinal stromal tumor (GIST). A: High NIH risk assessment correlated significantly with worse outcomes in patients with gastric GIST (P = 0.004); B: PTEN labeling indexes (LIs) ≥ 50% correlated significantly with favorable outcomes in patients with gastric GIST (P = 0.006); C: In patients with gastric GIST, those with Ki-67 LIs < 5% had significantly more favorable outcomes than those with Ki-67 LIs ≥ 5% (P = 0.004); D: CD44s positivity was a significant, favorable indicator for patients with gastric GIST (P = 0.006); E: For patients with small intestinal GIST, the immunophenotype of PTEN LIs ≥ 50% and Ki-67 LIs < 5% was a favorable indicator (P = 0.009); F: Gastric GIST patients with immunophenotype of PTEN LIs ≥ 50%, Ki-67 LIs < 5% and CD44s positivity had significantly more favorable outcomes than those with other immunophenotypes (P = 0.011).
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