Immunohistochemical Markers Can Be of Predictive Value in Hodgkin’s Lymphoma Response to Treatment. A Preliminary Study of 23 Cases.

Hodgkin’s lymphoma (HL) belongs to the most curable tumor diseases in adults and about 80% of patients can be cured with modern treatment strategies. However, some HL are primary refractory to usual treatments including a first line of anthracyclins based regimen and have more than 50% of residual disease after treatment. Currently, clinical parameters are considered as main relevant factors for prognosis. Herein, in order to predict value of some other factors on treatment response, we evaluate immunohistochemical markers of apoptosis, proliferation and of environmental non neoplastic cells in HL. A retrospective study was performed on pre-treatment biopsy specimen of 23 patients presenting with HL treated with the same anthracyclin based regimen, 8 primary refractory HL (non responders or relapse occurring within one year) and 15 good responders (free of disease for 2 or 3 years) to chemotherapy. These patients ranged in age from 23 to 52 years old (median= 36.5 years) for refractory HL and from 21 to 75 years old (median= 37.9 years) for good responders (n.s). All refractory HL, except one for whom histological type could not be defined because of a too small biopsy, had a nodular sclerosis (NS) histological type. The histological type was NS in 13 responding patients and mixed cellularity for the 2 others (n.s). The semi-quantitative immunohistochemical study used bcl2, p53, Ki67, TiA1 and c-kit antibodies. The results were statistically evaluated using a Wilcoxon sum rank test. Ki67 was strongly expressed on Hodgkin (Hg) and Reed-Sternberg (RS) cells whatever patients were refractory or responders to chemotherapy. By contrast, p53 and bcl2 had a significantly higher expression on Hg or RS cells in refractory patients (median= 90%&60%) compared to responding HL (median= 42.5 & 8%)( p=0.0001 & p=0.026 respectively). The cytotoxic marker TiA1 stained a significantly higher number of small lymphocytes in refractory HL (median= 53 per high power field (hpf)) compared to responding patients (median= 24/hpf)(p=0.0003). C-kit antibody was negative on Hg or RS cells but stained significantly more mastocytes in refractory HL (median= 13/hpf) comparing to responders (median= 3.8/hpf) (p=0.001). These results indicate that some immunohistochemical markers may be useful for predicting the response to therapy of HL. A high expression of bcl2 and p53 in refractory HL supports the notion that an intact apoptosis cascade is essential for killing effect of chemotherapy. The increase of TiA1 and c-kit positive cells emphasizes the importance of the environmental non neoplastic cells in HL. A larger study is mandatory to confirm these preliminary results.