Correlation of tumor markers p53, bcl-2 and cathepsin-D with clinicopathologic features and disease-free survival in laryngeal squamous cell carcinoma

Various recognized prognostic factors in squamous cell carcinoma (SCC) of the larynx influence the therapeutic options offered to an individual patient in order to extend the survival expectancy. Additional prognostic indicators are required in specific patient subgroups. The present study used a standard immunohistochemical technique in order to retrospectively evaluate the accumulation of p53 gene product and the immunoreactivity of bcl-2 protein and cathepsin-D as possible prognostic markers of laryngeal SCC. Formalin-fixed, paraffin-embedded tumor materials were obtained from a series of 64 patients with cancer of the larynx. Immunostaining was evaluated by computerized image analysis. The accumulation of p53 protein was found in 57.8% (37/64) of the patients and was associated with large tumor size. The percentage of p53-positive neoplastic cells increased in high-grade carcinomas, particularly when they simultaneously demonstrated cathepsin-D immunoreaction in stromal cells (P = 0.049); bcl-2 immunoexpression was found to be generally limited. Cathepsin-D immunostaining was observed in tumor parenchymal and stromal cells (31.25% and 37.5% of all cases, respectively); it was found to be useful in defining patient subgroups with differences in relapse-free survival. Among patients with positive lymph nodes, those with cathepsin-D immunopositive tumor cells were at higher risk for relapsing (P = 0.0395). Although the classical prognostic factors of laryngeal carcinoma retain their predominance, cathepsin-D immunoreactivity may serve as an additional prognosticator in specific patient subgroups

Cyclin D1 protein tissue detection in laryngeal cancer

Cyclin D1 (CCND1) is a set of periodic regulatory proteins that is believed to govern cell cycle transit from G1 into S phase. Overexpression of CCND1 leads to abnormal cellular proliferation which underlies processes of tumorigenesis; CCND1 can thus function as a cooperative oncogene in cell transformation. In the present study we investigate the immunohistochemical expression of CCND1 in a well-documented series of 58 laryngeal squamous cell carcinomas (LSCC) and search for statistical associations between CCND1 index and various clinicopathological parameters including several immunomarkers’ expression as well as patients’ disease-free survival. Tissue sections from archival paraffin blocks were stained using the avidin-biotin-peroxidase complex method; the H-295 rabbit polyclonal antibody was applied at dilution of 1: 150. The percentage of CCND1 immunoreactive tumor cells for each tumor was counted by an image analysis system. CCND1 staining was confined to cell nuclei and, in the examined samples, ranged from undetectable (i.e. 0% of tumor cells, n = 6) to the majority of tumor cells (i.e. 89% of tumor cells) with mean value: 15.73%. In tumor adjacent, non invasive lesions, strong CCND1 staining was noticed in areas with cellular atypia. In cases with nodal metastases, no change in CCND1 expression in the nodal metastases compared with the primary tumors was observed. p53 protein accumulation in malignant cells was positively linked with CCND1 index (Mann-Whitney U: 205.5, p = 0.034). CCND1 expression appears to be an early event in processes of tumorigenesis and tumor progression in some LSCC. Apart from p53 protein accumulation, CCND1 immunohistochemical expression does not seem to correlate with nodal metastasis, disease recurrence or any other clinicopathological prognostic indicator. Copyright (C) 2005 S. Karger AG, Basel

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