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Notes: Abstract Background: The aim was to investigate the expression of a panel of biomarkers such as prolactin (PRL), p53, Bcl-2, c-erb B2, Ki-67, CD44, and factor VIII-related antigen (FVIII-RA) in primary tumors of stage II and stage III breast cancer and its correlation with disease prognostication. Methods: The streptavidin-biotin peroxidase complex technique was used for the detection of these antigens. Cytoplasmic staining pattern was observed for PRL, Bcl-2, and Ki-67. Staining pattern for p53 was nuclear. Membranous and/or cytoplasmic staining was noted for c-erb B2 and CD44. Microvessel staining was noted for FVIII-RA. Results: Of the 93 primary breast tumors analyzed, positivity for PRL was noted in 82%, for p53 in 56%, for Bcl-2 in 73%, for c-erb B2 in 68%, and for Ki-67 and CD44 in 78% each. The microvessel count (MVC) for FVIII-RA ranged from 0.0 to 29.0, with a median of 6.0, which was used as a cutoff. MVC $ 6.0 was noted in 51% of breast tumors. With increasing tumor size, the higher frequency of positivity of MVC $ 6.0 (P 5 .0001), CD44 (P 5 .001), PRL (P 5 .002), and c-erb B2 (P 5 .008), and higher frequency of Bcl-2 negativity (P 5 .033), was noted. In stage III patients, a higher positivity of the following biomarkers was noted, compared with stage II patients: MVC $ 6.0 (P 5 .0004), PRL (P 5 .0002), c-erb B2 (P 5 .001), and CD44 (P 5 .005). Further, Bcl-2 positivity was significantly lower in patients with stage III disease compared with those with stage II disease (P 5 .024). In patients with nodal involvement, the frequency of c-erb B2 (P 5 .006), MVC $ 6.0 (P 5 .011), and PRL (P 5 .032) was higher than in those without nodal involvement. Moreover, in these patients, with the increase in the number of involved lymph nodes, there was a significant increase in frequency of CD441 (P 5 .0004) and PRL1 (P 5 .013) tumors. Abnormal expression of one biomarker was seen in 7% of tumors, of two biomarkers in 4%, of three in 15%, of four in 19%, of five in 28%, of six in 20%, and of all seven biomarkers in 7% of tumors. The frequency of an increasing number of biomarkers coexpressed was higher in stage III patients compared with stage II patients (P 5 .00003). In the total number of patients (n 5 93), tumors with Bcl-2 negativity (P 5 .00001), MVC $ 6.0 (P 5 .001), PRL positivity (P 5 .02), and CD44 positivity (P 5 .034) had a significantly poorer overall survival (OS) compared with their respective counterparts. In stage II patients (n 5 40), only p53 expression was significantly associated with reduced relapse-free survival (P 5 .009) and OS (P 5 .040). In multivariate analysis, p53 expression was an independent prognostic factor that influenced relapse-free survival (P 5 .034) of stage II breast cancer patients. However, it failed to attain statistical significance for OS. In stage III patients (n 5 53), tumors with Bcl-2 negativity (P 5 .0005) and MVC $ 6.0 (P 5 .039) had a significantly poorer OS compared with their respective counterparts. In multivariate analysis of stage III patients, Bcl-2 was the only independent prognostic factor (P 5 .001) for predicting OS. There was a significant association between coexpression of the biomarkers and OS (P 5 .001). The OS rates decreased with the increase in number of abnormally expressed biomarkers. Conclusions: p53 expression in primary tumors was an independent prognostic factor that influenced relapse-free survival in patients with stage II disease. In stage III patients, lack of Bcl-2 expression was independently associated with a poor prognosis and, thus, may be an indicator of aggressive phenotype.

Notes: Abstract PURPOSE: This study was undertaken to evaluate the clinical use of Bcl-2, c-Myc, and p53 oncoproteins, either singly or in combination, as prognostic discriminants relative to recurrence and overall survival in patients with Dukes B or C colorectal carcinoma. METHODS: Analyses were made on archival pathology tissues of 48 patients with colorectal cancer. The oncoproteins were localized using commercially available monoclonal antibodies: clone 124 for Bcl-2, 9E11 for c-Myc, and DO-7 for p53. The avidin-biotin peroxidase complex method was used. Patients were followed up for a period of 2 to 36 months. RESULTS: Expression of Bcl-2 and c-Myc was cytoplasmic, whereas nuclear p53 immunoreactivity was localized in the tumor cells. Sixty percent (29/48), 65 percent (31/48), and 37 percent (18/ 48) of the tumors showed overexpression of Bcl-2, c-Myc, and p53 oncoproteins, respectively. Fifty-four percent (18/ 33) and 100 percent (9/9) of moderately and poorly differentiated tumors, respectively, were positive for Bcl-2 (P〈0.01). No such correlation was noted for c-Myc and p53 oncoproteins. Univariate analysis showed that patients with Bcl-2 and c-Myc overexpression were associated with poorer overall survival than patients with Bcl-2-negative (P〈0.0124) and c-Myc-negative (P〈0.036) tumors. In addition, when patients were subgrouped according to Dukes stage, a statistically significant poorer overall survival was observed in Dukes C patients with Bcl-2-positive tumors (P〈0.017). Furthermore, multivariate analysis revealed that coexpression of three oncoproteins was predictive of a worse prognosis than for those individuals expressing none of the oncoproteins (P〈0.031) and only one positive oncoprotein (P〈0.014). CONCLUSION: These findings suggest that oncoprotein coexpression possesses significant prognostic and potential therapeutic value; incorporation of molecular markers into future prospective randomized trials is advisable.

Notes: Abstract Background: The goal was to investigate the potential correlation between overexpression of CD44, high microvessel count (MVC), and p21ras with length of relapse-free and overall survival in patients with colorectal adenocarcinomas. Methods: CD44, factor VIII-related antigen (FVIII-RA), and p21ras were localized immunohistochemically in patients with colorectal adenomatous polyps (n=8) and adenocarcinomas (n=98). The correlation between the expression of CD44, MVC in the areas with highest density, and p21ras with relapse-free and overall survival time was investigated. Data were analyzed statistically using univariate and multivariate systems. Results: In patients with adenomatous polyps, the positivity of CD44, FVIII-RA, and p21ras was 75%, 62%, and 88%, respectively. In patients with colorectal carcinomas the positivity of CD44 was 55%, and for p21ras it was 52%. The median of FVIII-RA was 4 MVC (range, 0.0 to 32.33). MVC was greater than 4 in 53% of the patients with colorectal carcinomas. In univariate analysis, a significantly longer relapse-free time (CD44:P=.0004; FVIII-RA:P=.0006) and overall survival time (CD44:P=.0001; FVIII-RA:P=.001) were observed for patients with CD44-negative tumors and MVC below 4 as compared to those with CD44-positive tumors and MVC greater than 4. Similar observations were noted in patients with Dukes B and C disease and the rectum as the site of tumor. In multivariate analysis, only CD44 correlated significantly with both relapse-free (P=.0003) and overall survival (P=.00001). Conclusion: Univariate analysis showed CD44 and MVC to be independent predictors of prognosis in colorectal carcinomas. Multivariate analysis showed that CD44 positivity was the most important indicator of an unfavorable prognosis for relapse-free and overall survival in patients with colorectal cancer. Thus, it can be deduced that whether CD44 is positive or negative in patients with colorectal cancer may have prognostic importance and in the future may be used as a factor in the pathologic evaluation of tumor specimens. This hypothesis needs to be tested prospectively in a larger number of patients.

Notes: Abstract Many genetic abnormalities disclosed even in somatic cells like peripheral blood lymphocytes may mark footprint(s) of malignancy(ies). The present cytogenetic study on peripheral blood lymphocytes of sporadic breast cancer patients (n = 20) and their first degree relatives (n = 39) reports abnormalities of chromosomes 16, 5, 12, and 17 respectively in 17.59%, 8.33%, 6.48%, and 5.57% cells of patients and 15.83%, 8.33%, 7.5%, and 5% cells of their first degree relatives. These common chromosomal abnormalities pave the way to assume why first degree relatives of sporadic breast cancer patients are at increased risk of developing the same or other malignancies.