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. 2006 Mar 28;12(12):1924-32.
doi: 10.3748/wjg.v12.i12.1924.

Molecular markers (PECAM-1, ICAM-3, HLA-DR) determine prognosis in primary non-Hodgkin's gastric lymphoma patients

Alexander Darom  1 , Ilias P Gomatos, Emmanuel Leandros, Emmu Chatzigianni, Dimitris Panousopoulos, Manousos M Konstadoulakis, George Androulakis
Affiliations

Molecular markers (PECAM-1, ICAM-3, HLA-DR) determine prognosis in primary non-Hodgkin's gastric lymphoma patients

Alexander Darom et al. World J Gastroenterol. .

Abstract

Aim: To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin's gastric lymphoma.

Methods: We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results.

Results: HLA-DR antigen expression was detected in 33 gastric lymphoma patients (91.7%) and 6 non-malignant patients (54.5%). PECAM-1 stained tumor cells of 10 patients (27.8%), endothelial cells of 9 patients (25%) and inflammatory infiltrate of 4 patients (40%) with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients (47.2%), while 5 non-malignant patients (50%) were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively (P=0.009 and P=0.003). In the univariate analysis, PECAM-1(+)/ICAM-3(-) and HLA-DR(-)/ICAM-3(-) patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns (P=0.0041 and P=0.0091, respectively). Those patients who were HLA-DR(+)/ICAM-3(+)/PECAM-1(-) (n=8) had a significantly higher survival rate compared to the rest of the group (n=24) (P=0.0289).

Conclusion: PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

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Figures

Figure 1
Figure 1
Positive membrane immunostaining (A) and endothelial staining (B) for PECAM-1 in diffusely growing lymphocytes (magnification 1X400). Gastric glands were identified as negatively stained.
Figure 2
Figure 2
Positive membrane immunostaining for ICAM-3 in diffusely growing lymphocytes (magnification 1X400) (A) and fluctuations of the mean ICAM-3 expression level according to tumor grade (B) and positive intracytoplasm immunostaining for HLA-DR antigen in gastric lymphoma lymphocytes (magnification 1X200) (C) with gastric glands indicated as negatively stained.
Figure 3
Figure 3
Five- year survival according to PECAM-1 (A) and HLA-DR antigen (B) expression (HLA-DR positive patients had expression of HLA-DR antigen in more than 15% of their tumor cells).
Figure 4
Figure 4
Decreased 5 –year survival rate in PECAM-1(+)/ICAM-3(-) (A), and increased 5-year survival rate in HLA-DR(+)/ICAM-3(+) (B) gastric lymphoma patients.
Figure 5
Figure 5
One hundred percent 5-year survival rate in HLA-DR(+)/ICAM-3(+)/PECAM-1(-) gastric lymphoma patients.
See this image and copyright information in PMC

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