Prognostic Role of Apoptotic, Bcl-2, c-erbB-2 and p53 Tumor Markers in Salivary Gland Malignancies

Abstract

Objective: The clinical characteristics and survival probability rate of 36 patients with salivary gland malignancies and 10 patients with benign salivary tumors were summarized in relation to the immunohistological analysis of the tumor, apoptotic-related markers and apoptosis rate. The expression of the markers examined – Bcl-2, c-erbB-2, p53 – was detected in paraffin sections of the tumors by the streptavidin-biotin peroxidase method following heat-induced antigen retrieval, and the apoptosis rate was determined by the TUNEL method. Results: The overall 5-year survival probability was 61% for patients with malignant tumors and 100% for those with benign tumors. The survival probability of patients over 60 at diagnosis was significantly lower than that of younger patients. Patients whose malignant tumors were larger than 2 cm at diagnosis had worse survival than those with smaller tumors. The survival probability of patients whose malignant tumors were located in the submandibular glands was significantly lower than that of patients whose malignancies were located in the parotid and minor salivary glands. The survival probability of patients who demonstrated positive staining for c-erbB- 2 or TUNEL was lower than for those with negative staining. Gender, the existence of concomitant non-salivary malignancies and ethnic origin had no significant impact on survival. Conclusions: Our results demonstrated significant positive staining in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue examined for TUNEL, c-erbB-2, Bcl-2 and p53, pointing to a biological role for all four markers in the tumorigenic process which is yet to be elucidated. Significant reduction in survival was related to the specific location of the tumor in the submandibular gland, its size and older age of patient. Survival was also found to be significantly reduced when positive staining was demonstrated in the tumor tissue for TUNEL or c-erbB-2, more so for concomitant positive staining of both markers. Clinically, the most important result of the current study is that the survival rate of the patients examined with salivary tumors larger than 2 cm, with positive staining for both TUNEL and c-erbB-2, was 0 (p = 0.0001)!

The prognostic role of phospho-Src family kinase analysis in tongue cancer

“…EGFR was shown to be involved in the pathogenesis of oral cancer (Nestor et al 2007), yet it was never studied in relation to either TUNEL or to phospho-Src family kinase which might be important with respect to further elucidating the pathogenesis of the disease. It has been demonstrated that this proto-oncogene ampliWcation and/or protein overexpression is associated with poor prognosis in breast carcinoma and other human neoplasms, including stomach, renal, pancreatic, ovarian and salivary gland carcinomas (Quenel et al 1995;Hanna et al 1999;Nagler et al 2003). Further credence for these results is found in the reported mutual pro-carcinogenic role for c-erbB-2 and phospho-Src family kinase, previously shown in other cancers (though never in oral SCC).…”

TUNEL – an efficient prognosis predictor of salivary malignancies

“…In this regard, it is interesting to note that previous studies found the level of positive TUNEL staining to be relatively high not only in salivary glands malignancies but also in oral cancer (Loro et al, 1999;Nagler et al, 1999Nagler et al, ,2003. Our results are also supported by multiple recent studies of various nonsalivary malignancies which demonstrated that high scores of Ki67 and p53 staining predict a higher tumourogenic grade, a higher rate of metastasis spread and a poorer prognosis, whereas low scores of Ki67 and p53 are associated with prognostically better histopathologic features (Saleh et al, 2000;Ben-Izhak et al, 2001Jalava et al, 2006).…”

DNA Methyltransferase Inhibitor, Zebularine, Delays Tumor Growth and Induces Apoptosis in a Genetically Engineered Mouse Model of Breast Cancer

“…The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay (R&D Systems) was conducted on formalin-fixed and paraffin-embedded sections as previously described (18). An avidin-conjugated horseradish peroxidase bound to the biotinylated DNA fragments was used to generate a brown precipitate in the presence of diamenobezidine (Vector Laboratories Inc.).…”