Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival.

AIMS: Metallothionein (MT) has been implicated in several aspects of cancer pathobiology, such as differentiation, proliferation, apoptosis and invasion. The aim of the present study was to evaluate the clinical significance of MT expression in mobile tongue squamous cell carcinoma (SCC). METHODS AND RESULTS: MT protein expression was assessed immunohistochemically on 49 mobile tongue SCC specimens, and was analysed in relation to clinicopathological characteristics, and overall and disease-free patient survival. All of the examined mobile tongue SCC cases showed MT positivity in tumour cells; however, neither MT overexpression nor staining intensity was significantly associated with clinicopathological parameters. MT cellular distribution was significantly associated with histopathological grade of differentiation and depth of invasion (P = 0.0188 and P = 0.0484, respectively). MT staining intensity was identified as a significant predictor of overall patient survival at both univariate (P = 0.0377) and multivariate (P = 0.0472) levels. Twenty-seven (55.10%) of the examined SCC cases showed MT positivity in squamous tongue epithelium adjacent to the tumour, the MT positivity being correlated with depth of invasion (P = 0.0281), vascular invasion (P = 0.0194), and the existence of lymph node metastases (P = 0.0194). CONCLUSIONS: MT may be implicated in the development and progression of mobile tongue SCC and could be considered as a useful clinical marker for patient management and prognosis.

Expression of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival.

BACKGROUND: DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, minimizing cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma (SCC). METHODS: MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. RESULTS: MSH2 expression was significantly associated with depth of invasion (P=0.0335), tumor shape (P=0.0396) and muscular invasion (P=0.0098). MLH1 expression was significantly associated with lymph node metastases (P=0.0484) and borderline with perineural invasion (P=0.0699). MGMT expression was significantly associated with depth of invasion (P=0.0472), tumor shape (P=0.0187), perineural invasion (P=0.0115) and lymph node metastases (P=0.0032) and borderline with vascular invasion (P=0.0755). MSH2 expression was significantly associated with disease-free patients' survival in univariate analysis (P=0.0441), being also identified as an independent prognostic factor in multivariate analysis (P=0.0451). CONCLUSIONS: The present study supported evidence for possible implication of MSH2, MLH1 and MGMT proteins in the formation and progression of mobile tongue SCC.

Peroxisome proliferator-activated receptor-γ in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.

PURPOSE: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor, implicated in various aspects of cancer biology, such as differentiation, proliferation, invasion and angiogenesis. The present study aimed to evaluate the clinical significance of PPAR-γ in mobile tongue squamous cell carcinoma (SCC). METHODS: PPAR-γ protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples obtained from an equal number of patients. PPAR-γ expression and intensity of immunostaining were statistically analyzed in relation with clinicopathological characteristics, mitotic index and patients' survival. RESULTS: Elevated PPAR-γ expression was more frequently observed in patients with reduced depth of invasion (P = 0.0111). Moderate/intense PPAR-γ staining intensity was more frequently observed in patients with no evidence of muscular infiltration (P = 0.0229) and reduced depth of invasion (P = 0.0176). Mobile tongue SCC patients presenting enhanced PPAR-γ expression had significantly longer overall and disease-free survival times compared to those with low PPAR-γ expression (log-rank test, P = 0.0162 and P = 0.0114, respectively). CONCLUSIONS: PPAR-γ immunoreactivity in mobile tongue SCC was correlated with clinicopathological characteristics crucial for patients' management and prognosis. PPAR-γ may be considered as a useful prognostic marker in mobile tongue SCC and a potential therapeutic target for tongue cancer chemoprevention and treatment.

Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongue.

BACKGROUND: Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. METHODS: Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. RESULTS: Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. CONCLUSION: Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue.

Women and squamous cell carcinomas of the oral cavity and oropharynx: is there something new?

PURPOSE: Incidence of squamous cell carcinoma (SCC) of the oral cavity and oropharynx is increasing in French female patients. The objective of this study was to study the clinical and demographic characteristics and the prognosis of this female population. Secondary outcomes were to determine if a subgroup of patient had a different prognosis. MATERIALS AND METHODS: A prospective study from 1989 to 2002 of all female patients presenting SCC of the upper aerodogestive tract was conducted. Data for 171 women were extracted. Clinical and histological features were analyzed using chi(2) and log-rank tests along with the Kaplan Meier method and multivariate analysis using the Cox regression procedure. RESULTS: Mean patient age was 62 years. Of the study population, 48.5% used tobacco and 34.5% used alcohol. The relative risk of death for overall and cancer-specific survival increased for patients below the age of 45 or over the age of 70 (95% Cl; 0.3-1.05; P = .0085). Tobacco consumption decreased cancer-specific and overall survival (P = .0008 and .0001, respectively). The other prognostic factors we found were tumor and nodal status, previous or simultaneous cancer, oral cavity primary site. CONCLUSIONS: Prognosis of oropharyngeal and oral squamous cell carcinomas is less favorable in females who smoke as well as in younger and older women. With these patients, the oversight must be closer. Smoking, however, should be stopped.

Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome.

To determine whether human papillomaviruses (HPV) positive tonsillar squamous cell carcinoma (SCC) represent a specific entity, we studied the prevalence of HPV association and of tobacco/alcohol exposure in a series of 52 cases of tonsillar SCC cases. p53, p16, and pRb levels, deregulated by viral oncoproteins were assessed. Forty patients reported tobacco/alcohol exposure, 10 reported no exposure. HPV DNA was found in 32/52 (62%) cases, (HPV16 genotype in 27). All patients with no history of tobacco-alcohol exposure presented HPV positive tumor (p=0.0008). A strong correlation was observed between positive HPV status, decrease in pRB and increase in p16 expression level. 5 year overall survival rate was higher in HPV16 positive patients than in HPV negative (71% versus 36%; p=0.023). HPV status remained a significant prognostic factor in multivariate analysis. Tonsillar SCC can thus be divided in HPV positive and negative subgroups with different oncogenesis and response to treatment.