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

Nagler, Rafael M.; Kerner, Hedviga; Laufer, Dov; Ben-Eliezer, Shoshana; Minkov, Ira; Ben-Itzhak, Ofer

doi:10.1016/s0304-3835(02)00265-3

Cited by 52 publications

(38 citation statements)

References 48 publications

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“…That is important with respect to both clinical-and pathogenesisrelated aspects of oral cancer, and the various characteristics of this cancer show that, indeed, a representative group of tongue cancer patients was analyzed in the current study. Both the total and the DFS survival probabilities were found to be similar to those found in other studies, as was the important predictive roles that tumor staging, grading, N, and depth values have (6,32). The fact that only a minority of the patients were smokers and that most of them were diagnosed at early stages is typical of previous Israeli tongue cancer series (32).…”

Section: Discussionsupporting

confidence: 82%

Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer

Nagler¹,

Bahar

Shpitzer

et al. 2006

Clinical Cancer Research

184

119

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Purpose: Oral squamous cell carcinoma (OSCC) is a common human malignancy. Circulatory epithelial tumor markers were previously investigated in the serum of OSCC patients but almost never in their saliva, in spite of the fact that there is a direct contact between the saliva and the oral cancer lesion. The purpose of the current study was to examine tumor markers in the saliva of OSCC patients. Experimental Design:We measured the concentrations of the six most studied epithelial serum circulatory tumor markers in the saliva of OSCC (tongue) patients. Results: Significant increases (of 400 %) in salivary concentrations of Cyfra 21-1, tissue polypeptide antigen, and CA125 were shown. Salivary concentrations of CA19-9, SCC, and carcinoembryonic antigen were increased without statistical significance. A concurrent analysis of the three significantly increased markers revealed sensitivity, specificity, and negative and positive predictive values of 71%, 75%, 71%, and 75%, respectively. Conclusions: The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.Oral squamous cell carcinoma (OSCC) is a common human malignancy, with an increasing incidence (especially in younger people) and a 5-year mortality rate of f50% (1 -4), which has not changed significantly in >50 years (5 -11). Its location and treatment in the mouth/face/neck result in a relatively high rate of related morbidity, as the treatment frequently results in a significant mutilation and compromised functions. OSCC includes both mobile (oral) and base of tongue cancer lesions. Most often, an oral cancer lesion is located at the lateral border of the tongue, whereas one located at the base of tongue is considered especially lethal. Clinically, it is important to note that the therapeutic modality currently offered to patients is based on traditional stage-predicting indices (based mostly on the tumor-nodemetastasis criteria) and on histologic grading. Unfortunately, these predictors are subjective and relatively unreliable, as often two tumors with identical staging and grading behave in totally different fashions, and although one responds to therapy, the other is lethal. Accordingly, there has been an ever-growing effort dedicated to the basic research of oral cancer, focusing on the identification of biological indicators for the diagnosis of its biological nature and aggressiveness. Circulatory tumor markers for OSCC were investigated in various studies (12 -21) and showed relatively moderate sensitivity and specificity values with relation to diagnosis, prognosis predicti...

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Section: Discussionsupporting

confidence: 82%

Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer

Nagler¹,

Bahar

Shpitzer

et al. 2006

Clinical Cancer Research

184

119

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“…Moreover, it may be of interest to note the reports which concern TUNEL staining and oral SCC. In our study related to tongue SCC tumors, we found a similar prevalence of positivity of TUNEL staining (48% vs 50%), also significantly correlated with poor prognosis [38]. …”

Section: Discussionmentioning

confidence: 61%

“…A similar stage-related role for c-erbB-1 related to an increase of SCC tumor burden and invasion was demonstrated by the dimethylbenzanthracene (DMBA)-induced tumor development in the animal model of hamster buccal pouch epithelium carcinoma [35, 36, 37]. Moreover, we have just concluded a study on a series of 55 patients with tongue SCC lesions in which c-erbB-2 was positively stained in 18% of samples (p < 0.0001) but in none of the surrounding nontumoral epithelium [38]. …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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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)!

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“…8,9 p53 and p27 staining methods are described in two other previous articles as a result of our group's investigating tongue cancer. 10,11 Skp2 staining. Five micron sections were deparaffinized with xylene and rehydrated in a series of ethanols.…”

Section: Methodsmentioning

confidence: 99%

Skp2 and salivary cancer

Ben‐Izhak

Akrish²,

Gan³

et al. 2009

Cancer Biology & Therapy

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Salivary malignancies are rare, heterogeneous, unpredictable in clinical behavior and seldom studied. Skp2 expression was examined in salivary malignancies (n = 75) for a prolonged period (20 years). In 40/75 (53%) cases Skp2 expression rate (staining level) was ≤4% while in the remainder (47%) it was >4%. Correlation between enhanced Skp2 and enhanced p53 staining levels was significant (p = 0.042), as were correlation rates between enhanced Skp2 and reduced p27 staining levels (p = 0.01) and enhanced Skp2 and enhanced TUNEL staining levels (p = 0.008). Survival probability rates dropped when Skp2 expression increased. Median patient survival for reduced-stained-tumor patients (≤4%) was 143 months and significantly lower, 49 months (p = 0.016), for enhanced-stained-tumor patients (>4%). Survival probability at five years was 82% for the former group (≤4%) and 47% for the latter (>4%). At 20 years, survival dropped to 35% and 18% respectively (p = 0.016). More extensive and aggressive therapy did not reduce mortality in patients with enhanced Skp2-expressing tumors. Significant correlations between poor survival and significantly altered expression rates of Skp2, p27, p53, TUNEL and heparanase in salivary malignancies, suggest a biological role in salivary cancer pathogenesis for these five markers. The findings may be used for prognostic and follow-up purposes.

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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

Cited by 52 publications

References 48 publications

Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer

Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer

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

Skp2 and salivary cancer

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