Immunohistochemical study on the prognostic value of CD44 antigen – marker of metastases – in gastric cancer and its correlation with selected molecular parameters

Michał Tenderenda^{1, 2}, Dorota Kupnicka³, Jan Berner⁴, *Konrad Wroński^{5, 6}

Summary
Introduction. Classical prognostic factors basing on clinico-pathological features are being replaced, due to rapid development of molecular biology, by modern molecular factors of potential prognostic value, including antigen CD44 expression as a metastizing marker in various types of carcinoma. CD44 is a glycoprotein of 85 kDa molecular mass, making a receptor for hyaluronic acid and other components of extracellular matrix, found on the surface of lymphocytes, fibroblasts and epithelial cells.
Aim. The aim of the study was evaluation of the prognostic value of CD44 antigen expression level as a metastizing marker in resectable gastric cancer and analysis of some correlations between the expression of this antigen and selected histoclinical parameters, protein products of cell-cycle regulatory genes and proliferation, angiogenesis and apoptosis markers.
Material and methods. Immunohistochemical analysis was performed on specimens obtained from radical stomach resections in 80 patients treated at the Department of Surgical Oncology, Medical University of Lodz, in the period 1992-1997 for gastric cancer stage I-IIIB (TNM-UICC). For immunohistochemical examinations, the LSAB system was used, designed for assessment of antigen expression including monoclonal antibody anti-CD44 (DAKO). Similar immunohistochemical procedure was used for determination of other examined molecular parameters. To determine AI apoptosis index and show up apoptosis in tumour cells, the TUNEL method was used according to standard procedure. In statistical analysis, Fisher’s exact test as well as Pearson’s test and Spearman’s test were applied to evaluate correlations between the analyzed variables. Evaluation of their influence on post-operative overall survival and disease-free survival was done by the Cox regression model.
Results. In presented study there was a statistically significant difference in the length of overall and recurrence-free survival correlating to the protein CD44 expression level in cancer cells – the highest minimum 5 year survival probability occurred in the group with the lowest CD44 expression. Moreover, there was a positive correlation between CD44 expression and malignancy degree, and non-linear correlation with a histological type according to the Lauren classification. There was also observed a positive correlation between CD44 and Ki67, and a negative one between P21 and RB and CD44.
Conclusions. The above results demonstrate a big value of immunohistochemistry in determination of prognosis in gastric cancer using CD44 expression and existence of mutual correlations between CD44 and the selected cell-cycle regulators.

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