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Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods.The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low.Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.

Summary Plasma prolactin (PRL) and carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 74 patients with adenocarcinoma of colon and rectum. The markers were correlated with disease stage, histological grade and progression/remission of disease. The circulating preoperative median PRL and CEA levels were significantly higher in colorectal cancer patients than in their respective controls. PRL was elevated in all Dukes stages and in all histological grades of the tumour whereas the rise in CEA was more pronounced in Dukes D. Out of 74 patients, 29% (21/74) developed recurrent disease and 31% (23/74) responded to the treatment. With regard to monitoring recurrence(s), the predictive value of PRL was 94% which was significantly greater than that of CEA which was only 62%. In patients who developed liver metastases PRL remained elevated whereas CEA showed more than 100-fold increase. Therefore, we feel that CEA is a better marker for monitoring patients who developed liver metastases. From our results, we suggest that PRL can be used as a better overall marker for detecting recurrence(s) in patients with colorectal adenocarcinoma.Recently, we have published data on circulating prolactin levels in patients with breast cancer (80% of these had advanced disease i.e. with stage III and IV). The data mainly concern relationship between circulating prolactin and histologic grade, estrogen-and progesterone-receptor (ER, PR) and 2 years postoperative survival (Bhatavdekar et al., 1990a). We have also found plasma prolactin useful both as an indicator of disease progression and as short-term prognosticator in patients with advanced breast cancer (Bhatavdekar et al., 1990b;1992). In light of the interesting and convincing results obtained by us in breast cancer patients, we have now tested the significance of prolactin in colorectal cancer, another common cancer in this region, by comparing simultaneously prolactin results with those of CEA.In this study therefore, we have compared the sensitivity and specificity of prolactin and CEA and thus the relative usefulness of these markers in monitoring recurrences in patients with colorectal adenocarcinomas. In addition, plasma prolactin and CEA levels were also correlated with disease stage and histologic grade. Plasma PRL and CEA were assayed using double antibody RIA kits (Diagnostic Products Co., USA). The assays were performed in duplicate with an intra-and inter-assay coefficient of variation (CV) of 3-5% and 5-8% respectively. PRL values > 15.0 ng ml-' for males, > 20.0 ng ml-' for premenopausal and > 10.0 ng ml-' for postmenopausal females were considered for % elevation. CEA levels above 5.0 ng ml-' was regarded as % elevated.Criteria for positive tests were: continual rise in the marker level after an initial fall or persistent high level of the marker as an indicator of relapse and/or no response to treatment. Statistical analysisThe statistical significance of differences between various groups was calculated by Mann-Whitney U-test. a-value

A retrospective study was performed on 69 breast cancer patients (stage II, N = 18; advanced disease, N = 51) in order to assess the prognostic value of circulating prolactin (PRL), CEA, CA 15-3, insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) by RIA/IRMA. These markers were compared with short-term prognosis (two years). Significant difference was observed only for PRL ( < 20.0 ng/ml vs. > 20.0 ng/ml), which provide an independent predictor of short-term prognosis in advanced breast cancer.

There is growing interest in assessing multistep carcinogenesis and predicting its course using different molecular markers. TP53 is a tumor suppressor gene and appears to be one of the molecular targets of tobacco-related carcinogens in oral cancer. The present study evaluated the role of p53 expression in patients with leukoplakia and carcinoma of the tongue. p53 expression was studied by immunohistochemistry. All patients with leukoplakia of the tongue were male tobacco users. Nuclear staining of p53 was observed in 79% of those patients. Fifty percent, 25% and 4% of the patients expressed 1+, 2+ and 3+ nuclear staining, respectively. When leukoplakia patients were graded according to histopathology, 67% had hyperplasia and 33% had dysplasia. Nuclear p53 accumulation was 88% in hyperplasia and 62% in dysplasia. In patients with tongue cancer, nuclear accumulation of p53 was seen in only 19% of the tumors, with a staining intensity of 1+ in 13%, 2+ in 2% and 3+ in 4% of the tumors. The prevalence of nuclear p53 positivity (79%) was significantly higher in patients with leukoplakia than in patients with tongue cancer (19%; chi2 = 34.32, r = -0.45, df = 1, p = 0.0001; odds ratio (OR) = 16.66, 95% CI, 5.25-52.86). Therefore, leukoplakia patients who show p53 expression have a higher risk of developing tongue cancer than those who do not show p53 expression. As the percentage of positivity of nuclear p53 was very low, none of the clinicopathological parameters or disease status showed any significant association with it. The interesting finding is that none of the female cancer patients showed nuclear p53 expression. Therefore, p53 accumulation is believed to be an early event in neoplastic progression of the tongue.