The cell-cell adhesion molecule E-cadherin has been shown to suppress invasive growth of epithelial cells in vitro, and loss of its expression is thought to be important in invasion and metastatic potential of epithelial tumors in vivo. We retrospectively studied the level of E-cadherin expression in 50 primary head and neck squamous-cell carcinomas (HNSCC) by immunohistochemical methods, on frozen sections, using anti-E-cadherin monoclonal antibody (MAb) 6F9. It concerned patients with different stages of carcinoma of larynx or oral cavity who had been treated with curative intention 30 months or more before. Percentages of membranous stained tumor cells were scored in 1 of 5 categories. Scores were generally low, as in 11/50 lesions < or = 5% cells were stained, and in 19/50 lesions only 6-25% cells showed membranous staining. In 9 lymph-node metastases evaluated, E-cadherin expression was in the same range as in the primary tumors. There was a significant correlation between the level of membranous E-cadherin expression in the primary tumor and the degree of differentiation. No relation was found with tumor size (pT) or regional lymph-node classification (pN). Nevertheless, 29 patients surviving> or = 30 months without evidence of disease had significantly higher levels of membranous E-cadherin expression in their primary tumors than 10 patients with unfavorable clinical course clearly related to recurrent and/or metastatic HNSCC. Moreover, this could only partially be explained by distinctions in differentiation grade between both groups. Our results suggest that membranous E-cadherin expression has prognostic importance in patients with HNSCC.
Docetaxel is an active drug in patients with advanced squamous cell carcinoma of the head and neck.
HLA class I and II antigen expression in routinely processed head and neck squamous cell carcinoma (HNSCC) primary lesions was evaluated. Paraffin embedded samples from 66 squamous cell carcinomas and 7 verrucous carcinomas were studied immunohistochemically using recently developed anti-HLA class I monoclonal antibodies (MAbs) HClO and HCA2, and anti-HLA-DR rabbit serum. Percent stained tumor cells were scored in I of 5 categories. The scores of 40 tumors were compared t o the staining results obtained on frozen sections of the corresponding lesions, including those of the anticlass I MAb W6/32. High percentage-matched scores for paraffin and frozen sections were obtained, with HClO vs. HCIO, HClO vs. W6/32, and anti-HLA-DR vs. anti-HLA-DR showing the best correlations. In the squamous cell carcinomas HLA class I expression was high (Le., in 49/66 lesions more than 50% cells were stained), and correlated with the degree of differentiation, and inversely with the modified Jakobsson score. HLA class II expression (more than 5% cells stained) was found in 21/66 tumors and correlated inversely with the degree of differentiation. All verrucous carcinomas exhibited very high HLA class I expression, whereas class II was locally expressed in 517 lesions. Comparison of 4 subsites of HNSCC showed that carcinomas of the oral cavity had the highest HLA class I expression. This suggests susceptibility to CD8+ T cells, and together with the well developed submucosal lymphoid tissue, makes the oral cavity carcinomas probably well suited for local immunotherapeutic approaches in HNSCC.HLA antigens are supposed to play a role in the host's immune response towards neoplastic cells. On a variety of cancer cells both defective HLA class I and de novo class 11 expression have been described, mostly using immunohistochemistry on frozen tissue samples . Low expression of HLA class I antigens correlates with poor differentiation in colorectal cancer (Momburg et al., 1986) and in larynx carcinoma , and with poor prognosis in patients with loco-regional melanoma metastases (van Duinen et al., 1988). HLA class I1 expression in primary melanoma is associated with shorter disease-free survival (Brocker et al., 1985). The significance of HLA expression on tumor cells in relation to immunotherapy is mainly speculative, and has seldom been investigated. High HLA class I1 expression in regressing melanoma lesions following recombinant interleukin-2 (rIL-2)-based immunotherapy has been described by Rubin et al. (1989).Immunohistochemical analysis of HLA antigen expression is largely restricted to fresh frozen tissue. Routine tissue processing, i.e., formaldehyde-fixation and paraffin-embedding , denatures the antigens, and as a result the reactivity of most antibodies is lost. HCA2 and HClO MAbs, however, were prepared against free denatured HLA-A and -B locus heavy chains, respectively, and found to be reactive in paraffin sections of normal tissues (Stam et al., 1990). For detecting HLA class I1 antigen expression in frozen and paraffin secti...
Summary:MDS are mostly seen in the elderly. While the overall incidence is about 2-4 per 100 000 per year, this is 20-30 per 100 000 per year in the population over 70 years. 1 The cliniThirty-five patients with myelodysplastic syndromes (MDS) were treated with BMT between 1986 and 1994.cal course of MDS varies from an indolent form to a rapidly fatal disease. Patients die from infection or bleeding, comTheir median age was 41 years (range 23-60). Thirteen patients had transfusion-dependent refractory anaemia plications of transfusion, or acute leukaemia. Conventional treatment is not curative. 2 In cases with excess of blasts or (RA). Twenty-two patients suffered from more advanced stages of MDS, 15 being in complete remission following progression to AML, intensive chemotherapy may result in CR in 50-60% of patients, but the median (CR) after chemotherapy. In 31 recipients, pretransplant conditioning consisted of cyclophosphamide and remission duration is usually less than 12 months, while a median survival following chemotherapy of 7-15 months TBI with or without the addition of idarubucin; four patients were conditioned with other schedules. Donors has been recorded. 3,4 An increasing incidence of MDS is being observed in relatively young patients surviving after were genotypically HLA-identical and MLC-negative siblings in 32, and others in three cases. All patients chemotherapy, immunotherapy and/or radiotherapy for other diseases. These treatment-related MDS have an even received a graft depleted of 98% of T lymphocytes using counterflow centrifugation. Fourteen patients are alive worse clinical course. 4,5 Allogeneic BMT offers a potentially curative treatment and in continuous remission with a median follow-up of 20 months (range 15-113) after BMT. Seven patients for younger MDS patients. In a recent review, the probability of 5-year disease-free survival (DFS) following relapsed between 3 and 18 months after BMT and subsequently died. Fourteen transplantation-related deaths BMT in a group of 93 patients was 40%, while the actual DFS varied from 35 to 63% in six smaller studies with occurred. Outcome in patients under and over 40 years old was comparable. The probability of disease-free surshorter follow-up. 6 Median age in these patient groups ranged from 23 to 36 years, and a younger age was found to vival (DFS) at 2 years after BMT was 39% (95% confidence interval (CI), 22-56%). Considering patients with be a favourable prognostic factor. We report a retrospective study of our results of BMT in a group of 35 adults with HLA-identical and MLC-negative sibling donors transplanted for RA (n = 11) or more advanced stages of MDS. This patient group is relatively old as compared to the previously published series. 6 MDS in CR (n = 14), the probabilities of DFS were 73% (95% CI, 47-99%) and 42% (95% CI, 15-69%), respectively. This indicates that BMT with lymphocytedepleted grafts can cure a substantial number of relaPatients and methods tively old patients with MDS, especially when grafts from HLA-identi...
Polyethylene glycol-modified recombinant human interleukin-2 (PEG-IL-2) represents a cytokine with prolonged circulatory half-life and increased antitumor activity as compared to recombinant interleukin-2 (rIL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line-10 tumor cells into the flanks of strain-2 guinea-pigs results in a fast-growing tumor and regional lymph-node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5-6 animals were treated with repeated intratumoral and perilymphatic rIL-2 or PEG-IL-2 injections. PEG-IL-2 caused significant growth inhibition of both the primary tumor and the regional lymph-node metastases at lower doses and with less frequent administration than rIL-2. The best schedule for PEG-IL-2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (p less than 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-10 tumor cells, whereas no cures were seen after rIL-2 injections. PEG-IL-2 therefore appears to be a valuable substance for intratumoral immunotherapy.
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