Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.
This is a retrospective study of Hodgkin's disease in children less than 15 years of age who were registered at Tata Memorial Hospital in India from January 1985 through December 1990. Clinicopathologic characteristics and response were evaluated in 147 patients and survival was calculated in 187. There were 126 boys and 21 girls (6:1). All patients were treated with combination chemotherapy and involved field radiotherapy. The COPP schedule was given to 108 patients. COPP/ABVD to 33, and ABVD to 6. Ninety-three patients (63%) had stage I or II disease and 54 (37%) had stage III or IV disease. B symptoms were observed in 65 patients (56%) and bulky disease in 40 (27%). Histologically, the most common subtype was mixed cellularity, seen in 95 patients (65%). Complete response was observed in 136 (89%), partial response in 6 (4%), and there were 4 treatment-related deaths. Relapse has been observed in 11%. Seven-year actuarial survival was 73% and event-free survival was 64%. Median survival has not yet been reached, with a median follow-up of 36 months.
Immunohistochemical staining was performed on 145 biopsies with a diagnosis of undifferentiated or poorly differentiated tumor in order to classify them into lymphoid, epithelial, or mesenchymal in origin. It was possible to arrive at a histogenetic diagnosis on immunostaining in 85.5% of cases. Immunostaining confirmed the diagnosis in 32.4% and contributed to diagnosis in 53.1%. Malignant lymphoma was the most common diagnosis (35.9%), followed by carcinoma (23.4%). A panel of antibodies consisting of anti-common leucocyte antigen (LCA), anti-epithelial membrane antigen (EMA), anti-cytokeratin (CK), anti-low to intermediate molecular weight cytokeratin (CAM 5.2), anti-S-100 protein (S-100), and anti-vimentin (VM) may resolve, to a large extent, some of the common diagnostic problems.
Fas and Fas ligand expression were investigated in twenty two cases of classical Hodgkin's disease (HD) by immunohistochemistry. While Reed-Sternberg (RS) cells in 7/22 (32%) cases expressed Fas ligand, reactive lymphoid cells expressed Fas ligand in only 2 (9%) cases. In 20/22 (91%) cases, the RS cells expressed Fas. A higher proportion of RS cells in the nodular sclerosis subtype expressed Fas as compared to the mixed cellularity subtype. In 18/22 (82%) cases, Fas expression was also noted in the reactive lymphoid cells. In eight cases, the reactive lymphoid cells were also analyzed by flow cytometry and a majority of them were CD4+CD45RO+. Most of these activated T-cells expressed Fas but were negative for Fas Ligand. To investigate the co-expression of Fas and Fas Ligand in the RS cells, six cases were subjected to Fas and Fas ligand immunostaining on consecutive sections. The co-expression was documented in the RS cells in four of six cases. These six cases with expression of both Fas and Fas ligand were investigated for the incidence of apoptosis. There was no statistically significant relationship between expression of Fas on reactive cells, expression of FasL on RS cells and the proportion of apoptotic reactive cells. In all these cases apoptosis was not observed in the RS cells. Thus Fas - FasL interactions may not lead to apoptosis of the RS cells.
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