Squamous cell carcinoma of the tongue: the prevalence and prognostic roles of p53, Bcl-2, c-erbB-2 and apoptotic rate as related to clinical and pathological characteristics in a retrospective study.

In the current study, we examined the clinical characteristics and survival probability rates of 116 patients treated for squamous cell carcinoma (SCC) of the tongue. In 55 randomly selected patients these data were correlated with the immunohistological analysis of the tumor and apoptosis-related markers, p53, Bcl-2, c-erbB-2 (Her-2/neu), and to the apoptosis rate assessment by the terminal dUTP nick-end-labeling (TUNEL) method. The overall 5-year survival probability was 55%, which might be the result of the low incidence of smoking and/or alcohol consumption among the patients (21%), the early diagnosis (65% at Stages I-II) and the low histological grades (91% good-moderate). Radiotherapeutic or surgical treatment of the neck did not alter the survival probability achieved by local surgery for Stage I patients, but significantly improved survival for Stage II patients. Independent tumor-related variables which significantly worsened the probability of survival were found. Concomitant non-oral cancer was found to be a poor variable for prognosis prediction. Positive staining of p53, TUNEL (apoptosis rate), c-erbB-2 and Bcl-2 was found in 60, 48, 18 and 15% of the lesions, respectively (P<0.0001). The possible biological significance of these markers in tongue SCC is discussed in relation to the current literature, and an independent role for TUNEL and p53 is suggested.

The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma.

BACKGROUND: Loss of the cell-cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma. MATERIALS AND METHODS: The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin-embedded tissue sections from 80 patients with colorectal carcinoma. RESULTS: Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression. CONCLUSIONS: Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma.

Pediatric nasopharyngeal carcinoma: better prognosis and increased c-Kit expression as compared to adults.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) in children is distinguishable from the adult form by its close association with Epstein-Barr virus (EBV) infection, a higher rate of undifferentiated histology, and a greater incidence of advanced locoregional disease. PATIENTS AND METHODS: Sixteen NPC patients, < or =20 years of age were identified from our 1976-2001 tumor registry records. Clinical stage, treatment, recurrence, and survival were evaluated. Sections were stained by immunohistochemistry for p53, Bcl-2, Ki67, and c-Kit and by in situ hybridization for EBER. Obtained data were compared to 32 adult patients. All patients had undifferentiated or non-keratinizing NPC. RESULTS: EBER was positive in 100% of children, compared to 90% of adults. Comparing children to adults, median Ki67 index was 49% and 30%, p53 positive tumors were 69% and 94%, positive Bcl-2 was 63% and 72%, and positive c-Kit was 88% and 28%, respectively. CONCLUSION: No parameter had significant predictive values for survival, although c-Kit expression had a trend for better prognosis in the pediatric group. By univariate analysis of all 48 cases, positive c-Kit was associated with better survival (P = 0.029), largely due to the better survival of the pediatric group. By multivariate analysis, increased stage (P = 0.006) and older age (P = 0.044) correlated with worse prognosis.

Prognostic role of apoptotic, Bcl-2, c-erbB-2 and p53 tumor markers in salivary gland malignancies.

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)!

Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma.

BACKGROUND: Low levels of p27(Kip1) are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27(Kip1) for degradation, was overexpressed and was inversely related to p27(Kip1) levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2-dependent p27 degradation was recently discovered, but its role in human malignancies is unknown. METHODS: Quick-frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, transferred to nitrocellulose, and probed with highly specific monoclonal antibodies directed against Cks1, Skp2, and p27(Kip1). The expression of Cks1 was also examined by immunohistochemistry using formalin-fixed, paraffin-embedded tissue sections from the same patients. RESULTS: A strong correlation was found between Cks1 levels and Skp2 expression and loss of tumor differentiation. A significant inverse relation was also observed between levels of Cks1 and p27(Kip1) and overall survival. CONCLUSIONS: The results of the current study suggest that increased expression of Cks1 may have an important causative role in decreasing levels of p27 in patients with aggressive colorectal carcinoma.