Heparanase expression levels inversely correlate with the survival rates of salivary gland cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy and an attractive target for anticancer drug development.

Molecular remission according to FISH and multiplex RT-PCR can be achieved by imatinib within 1 yr of therapy. There is a good correlation between the FISH, multiplex and RQ-PCR results in terms of the kinetics of disappearance of the BCR-ABL transcript and the predictability of each method for the other. Although RQ-PCR is the most sensitive method for molecular follow-up, FISH and multiplex RT-PCR can be used as complementary tools, at least during the early period of treatment.

We have earlier shown an advantage in overall survival for malignant lymphoma (ML) patients who received combined Interleukin-2 (rIL-2) and interferon alpha (IFN-alpha) immunotherapy after autologous stem cell transplantation (AutoSCT) in comparison with historic controls. On the basis of these results, we initiated a control prospective randomized multicenter 2-arm study, comparing the same combined immunotherapy treatment versus control for patients with malignant lymphoma after AutoSCT. One hundred nine patients were included in this study. After AutoSCT, patients were randomized either to the treatment group or to the control group. Patients in the treatment group received daily subcutaneous injections of rIL-2 6x10 IU/m/d for 5 consecutive days followed by 2-weeks rest period. Subsequently, they were treated daily with rIL-2 6x10 IU/m/d combined with INF-alpha 3x10 U/d for 5 consecutive days per week for 4 consecutive weeks. After 4 weeks of rest, IFN-alpha 3x10 U was administered for the next 6 months 3 times per week. Patients in the control group were followed up at the outpatient clinic. There was a significant enhancement of survival (P=0.05) and a clear trend in disease-free survival in favor of NHL patients receiving post-AutoSCT immunotherapy, in comparison with the control group. Eighty-nine percent of patients with NHL treated with immunotherapy were alive and 64% were disease free. In the control group, 66% of patients survived and 46% were disease free. Among the HL patients no significant differences were observed regarding survival, disease-free survival, and relapse rate. No serious toxicity events were observed. These results suggest that outpatient administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in NHL patients, but not HL patients after AutoSCT.

Salivary malignancies are rare, heterogeneous, unpredictable in clinical behavior and seldom studied. Skp2 expression was examined in salivary malignancies (n = 75) for a prolonged period (20 years). In 40/75 (53%) cases Skp2 expression rate (staining level) was ≤4% while in the remainder (47%) it was >4%. Correlation between enhanced Skp2 and enhanced p53 staining levels was significant (p = 0.042), as were correlation rates between enhanced Skp2 and reduced p27 staining levels (p = 0.01) and enhanced Skp2 and enhanced TUNEL staining levels (p = 0.008). Survival probability rates dropped when Skp2 expression increased. Median patient survival for reduced-stained-tumor patients (≤4%) was 143 months and significantly lower, 49 months (p = 0.016), for enhanced-stained-tumor patients (>4%). Survival probability at five years was 82% for the former group (≤4%) and 47% for the latter (>4%). At 20 years, survival dropped to 35% and 18% respectively (p = 0.016). More extensive and aggressive therapy did not reduce mortality in patients with enhanced Skp2-expressing tumors. Significant correlations between poor survival and significantly altered expression rates of Skp2, p27, p53, TUNEL and heparanase in salivary malignancies, suggest a biological role in salivary cancer pathogenesis for these five markers. The findings may be used for prognostic and follow-up purposes.

Salivary malignancies are rare, heterogeneous, unpredictable in their clinical behavior and seldom studied. This study focused on examining the expression of mutated p53, the most prevalent mutated gene related to human cancer, in a rather large cohort of salivary malignancies (n = 70) and for a prolonged period (20 years). P53 was found to be a most powerful predictor for poor survival and more so when the tumor concurrently expressed TUNEL and heparanase markers, dramatically dropping the survival probability of the patients to 0! Survival probability at 6 years for patients with tumors stained negatively vs. positively for p53, TUNEL and heparanase was 100% vs. 49% while at 18 years this probability dropped to 67% vs. 0%, respectively (p = 0.023). Significant correlation rates were found between age and poor survival, age and p53, and p53 and other co-existing malignancies. These findings support mutated p53 as a prognostic predictor and a pivotal player in salivary carcinogenesis. Significantly more extensive therapy applied to salivary p53-positive patients did not improve mortality rate, questioning the justification for such extensive therapy and emphasizing the need to understand p53, TUNEL and heparanase biological pathways and develop additional therapeutic tools for fighting salivary cancer.