Evaluation and clinical correlation of bone marrow angiogensis and level of serum angiogenic factors in acute leukemia

In this study serum angiogenic factors vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF] and tumour necrosis factor a [TNF a]] and cellular angiogenic factors [VEOF and VEGF-R2] were studied in 50 newly diagnosed acute leukemia patients, they were 24 ALL and 26 AML patients. The correlations of the studied angiogenic factors to each other and to the patients' survival and disease outcome were studied. During the follow-up period of 6 months, 22 patients died and 28 patients remained alive from whom 11 patients were refractory and 17 patients achieved complete remission. On comparison between pretreatment concentration levels of measured serum angiogenic factors [VEOF, TNF-alpha and HOF] in ALL, AML and the control group, all the comparisons were statistically significant [p<0.0001, <0.0001 and 0.02 1 respectively]. All serum markers were higher in AML group than control group, but only VEOF showed statistically significant elevation [p<0.0001], while in ALL patients, all markers were significantly higher than control group [p=0.01]. When comparing ALL and AML cases according to cellular angiogenic factors detected by immunocytochemistry, cellular VEGF-R2 was slightly higher in ALL group, while cellular VEGF was slightly higher in AML group. The comparisons were statistically non-significant for both angiogenic factors. As regards response to therapy, in ALL, cases with high sVEGF showed a statistically significant lower rate of complete remission than cases with low sVEGF [p=0.041]. The same results were obtained for AML but the comparison did not reach a significant level [p=0.082]. Serum VEOF was the only reliable marker to predict relapse in ALL [p=0.009] and AML [p=0.049]. On comparing serum VEGF to the outcome in ALL, high sVEGF cases showed a statistically significant higher rate of death than low sVEGF cases [prO.05], while in AML, the same results were obtained but the comparison did not reach a significant level. As regards the survival time, cases with low sVEGF level showed higher mean survival and 6-month survival than cases with high sVEGF level p=0.03]. A significant negative correlation was detected between serum VEGF and serum TNF-a [correlation coefficient [r]=-0.642, p<0.0001]. Conclusion: Serum angiogenic factors [VEGF, TNF-alpha and HOF] are markedly increased in cases of acute leukemia compared to normal controls. Cases with high sVEGF showed higher rate of death than cases with low sVEGF, so its targeting may provide a potent novel therapeutic approach in acute leukemias. VEGF may also be useful as a new prognostic factor and a predictor of relapse in different types of acute leukemia. Further studies with larger number of patients and longer duration of follow-up are recommended to throw more light on the significance of other angiogenic factors in relation to acute leukemia

Study of the expression of survivin and mutant p53 in pediatric acute lymphoblastic leukemia

Childhood acute lymphoblastic leukemia is the most common malignancy in children with a yearly incidence of 31/1000000 children younger than 15 years old. The peak incidence of childhood ALL is between 3 and 6 years of age with male predominance. The relative frequency of pediatric ALL in the NCI-Cairo University is 35.5% for the years 2003-2004. In this study survivin and mutant p53 expressions were studied in 64 newly diagnosed pediatric ALL patients. Their associations to the different prognostic factors of ALL and their association to each other were studied. In this study, 21 out of 64 ALL cases [32.8%] showed positive expression of survivin [17 patients were moderately positive, 2 patients were strong positive and 2 patients were weak positive] and 24 out of 64 studied ALL cases [37.5%] demonstrated positive expression of p53 [20 patients were strong positive, 3 patients were moderately positive and 1 patient was weak positive]. On comparing survivin expression with the different prognostic factors of ALL, the results were statistically significant as regards the percentage of blasts in the peripheral blood [p-value = 0.0068], and the percentage of blasts in the bone marrow [p-value = 0.05]. As regards LDH, ALP, and uric acid serum concentrations, no statistically significant differences were found [p-value = 0.154, 0.52 and 0.41 respectively]. No significant association was found between survivin expression and hepatosplenomegaly. As regards p53 expression compared with the different prognostic factors no statistically significant results were found. According to immunophenotyping [IPT], survivin was positive in 5 out of 14 cases [35.7%] of proB-ALL, 0% [0/11] C-ALL, 29.2% [7/24] preB-ALL, 75% [6/8] mature B-ALL and 42.9%[3/7] T-ALL. The results were statistically significant [p-value = 0.046], while p53 was positive in 4 out of 14 cases [28.5%] of proB-ALL, 36.4% [4/11] C-ALL, 41.6% [10/24] preB-ALL, 50% [4/8] mature B-ALL and 28.6% [2/7] T-ALL. The results were statistically non significant. No significant correlation was found between survivin and p53 expression in the studied ALL cases [p-value = 0.872]. In this study, a total of 23 patients successfully completed induction phase. All of them achieved complete remission. Two patients developed isolated bone marrow relapse at a median period of 7.5 months. The disease free survival for the 23 patients was 89.6% at a median of 11 months. The DFS for P53 positive [12/23] and p53 negative [11/23] patients was 91.7% and 90.9% respectively [p= 0.90]. The DFS for survivin positive [11/23] and survivin negative [12/23] patients was 85.7% and 93.7% respectively [p=0.49]. In conclusion, we could not find any association between p53 and survivin expressions and the different prognostic factors of pediatric ALL patients, [the only statistically significant results were obtained when comparing the blast count% in both the peripheral blood, and the bone marrow between survivin positive and survivin negative cases]. As regards the comparison of survivin expression and phenotyping of the studied patients, it was not expressed in C-ALL cases which are known to have a good prognosis. Further we could not decide whether positive p53 or survivin in ALL patients had an impact on DFS. Further studies with larger number of patients and longer duration of follow up are recommended to throw more light on the significance of p53 and survivin in relation to ALL patients

Study of some tumor markers and their use in breast cancer relapse

Tissue polypeptide antigen [TPA], cancer antigen 15-3 [CA15.3] and carcinoembryonic antigen[CEA] were evaluated by ELISA in 61 patients of breast cancer to evaluate their role in breast cancer relapse, as well as 16 apparently healthy age matched females as control group. The patients were divided into: Post operative group [26 patients] and relapse group [35 patients], eight patients with local recurrent breast cancer and 27 patients with distant metastasis at different sites. Statistically significant elevation was found for the three tested markers in the relapse group compared to the control and post operative group [P < 0.001], also a statistically significant elevation was found in CEA, CA15.3 and TPA in metastatic group compared to local recurrence group [P = 0.01, 0.03 and 0.01 respectively]. TPA level was statistically higher in grade III than in grade II [P = 0.0009]. In relapse group, right sided tumor showed statistically significant elevation of CEA, TPA than the left sided tumor [P = 0.005 and 0.03 respectively]. According to TNM staging CEA showed statistically significant correlation between Ml and Mo [P = 0.01]. In relapse group CA15.3 showed a statistically significant difference between tumor sized > 2 cm and tumor < 2cm [P = 0.04]. In the relapse group there was a statistically significant correlation between multiple lesions and solitary lesions [P = 0.02]. Among the same group there was a significant positive correlation between the percentage of L.N positivity and each of CEA, CA15.3 and TPA. [r - 0.04, 0.42 and 0.51] [P - 0.03, 0.02 and 0.003 respectively]. Another positive correlation was found between tumor size and L.N positivity [r = 0.44] [p = 0.01]. In both post - operative and relapse group there were positive correlations between CA15.3 and CEA [r - 0.45 and 0.56] [P = 0.02 and 0.001 respectively] Positive correlations were found similarly between TPA and CEA [r - 0.50] [P - 0.003] and CA15.3 and TPA [r - 0.57] [P<0.001] in relapse group. Evaluation of tumor markers, separately showed acceptable accuracy profiles regarding the relapse and distant metastatic patients, with CEA being the most sensitive marker, followed by CA15.3 and lastly TPA. In relapse group the most useful combinations for diagnosis could be [CEA and CA15.3] double combination and [CEA, CA15.3 and TPA] triple combination. In distant metastasis group, the combination of choice could be [CEA and TPA] or [CEA and CA15.3] double combinations and CEA, CA15.3 and TPA] triple combination. The use of the 3 markers merit is to be tried in greater number of breast cancer patients

Prognostic significance of some tumor markers in head and neck carcinomas

Carcinoembryonic antigen [CEA], ferritin, tissue polypeptide antigen [TPA] and alkaline phosphatase [ALP] isoenzymes were evaluated in 41 patients with head and neck cancer before and [2-6] months after receiving treatment. The study included as well 13 apparently healthy age matched individuals as control group. Statistically significant elevation was found for CEA, ferritin, TPA and ALP in the patients before treatment compared to the control [P = 0.001, 0.0001, 0.04, 0.001 respectively], another statistically significant elevation was found for all the studied markers in patients before treatment compared to their levels after treatment [P < 0.001 for CEA, ferritin, TPA and ALP and 0.001 for PALP]. Ferritin was the only marker that showed statistically significant elevation in grade III compared to grade I and II [p - 0.001]. A significant elevation could be detected in the level of TPA and PALP in patients with positive regional L.N mecastasis compared with those without regional L.N metastasis [P = 0.03 and 0.04 respectively]. A statistically significant positive correlation was detected between ferritin level and tumor grade [r = 0.5, P 4 X 001]. Also a statistically significant negative correlations were found between TPA and regional L.N metastasis [r = -0.3, P = 0.04] and between ALP and CEA mean values in treated patients [r = -0.4, p = 0.009] Evaluation of tumor markers, separately revealed that CEA and then ferritin showed higher sensitivity [97.6 percent and 94.6 percent respectively], followed by ALP and TPA [75.6 percent and 5 8.3 percent respectively]. The specificity of CEA was higher than the other studied markers [100 percent]. As regards double combination, it was found that [CEA and ferritin] combination showed the highest sensitivity and specificity followed by [CEA and ALP] and [ferritin and ALP] [sensitivity, [either abnormal] 89 percent, 90 percent and 81 percent for the three previous combination respectively, [both abnormal] 46 percent, 23 percent, and 32 percent respectively] [specificity, "either abnormal" and "both abnormal was 100 percent and 92 percent for [CEA and Ferritin] and [CEA and ALP] respectively, and 100 percent and 85 percent for [ferritin and ALP]. All the triple combinations showed much lower sensitivity and specificity. Sixty one of untreated patients gave PALP bands. After treatment a reduction in PALP percentage was seen in 82 percent of patients. This reduction in PALP activity correlated to tumor stage, being one of the prognostic factors. A strategy requiring 2 or more markers to be abnormal while having both sensitivity and specificity high in monitoring head and neck cancer patients or detecting recurrence could be attained by trying more tumor markers to make firm conclusion