Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status.
AIMS: To correlate vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma with the clinicopathological characteristics and prognosis; and to assess whether p53 gene status is associated with VEGF expression in human cancers. METHODS: Tumour specimens from 45 patients with oral squamous cell carcinomas were examined. Expression of VEGF was determined using an immunohistochemical method, and a tumour was considered positive when more than 5% of the neoplastic cells showed VEGF immunoreactivity. The p53 gene status was screened using a polymerase chain reaction--single strand conformation polymorphism analysis. RESULTS: VEGF positive staining was detected in 19 (42.2%) of the 45 cases. VEGF immunoreactivity did not correlate with the histological degree of tumour differentiation, clinical stages, or lymph node metastasis. The patients with VEGF positive tumours had a significantly worse prognosis than those with VEGF negative tumours. The five year overall survival rate of the VEGF negative patients was 76.5%, as compared with 48.8% for the VEGF positive patients. No significant association between VEGF expression and the p53 gene status of the tumours was found. CONCLUSIONS: VEGF is a good prognostic indicator of the survival of patients with oral squamous cell carcinoma. The p53 gene status does not seem to be associated with VEGF expression in these cancers. (+info)
Use of wood stoves and risk of cancers of the upper aero-digestive tract: a case-control study.
BACKGROUND: Incidence rates for cancers of the upper aero-digestive tract in Southern Brazil are among the highest in the world. A case-control study was designed to identify the main risk factors for carcinomas of mouth, pharynx, and larynx in the region. We tested the hypothesis of whether use of wood stoves is associated with these cancers. METHODS: Information on known and potential risk factors was obtained from interviews with 784 cases and 1568 non-cancer controls. We estimated the effect of use of wood stove by conditional logistic regression, with adjustment for smoking, alcohol consumption and for other sociodemographic and dietary variables chosen as empirical confounders based on a change-in-estimate criterion. RESULTS: After extensive adjustment for all the empirical confounders the odds ratio (OR) for all upper aero-digestive tract cancers was 2.68 (95% confidence interval [CI] : 2.2-3.3). Increased risks were also seen in site-specific analyses for mouth (OR = 2.73; 95% CI: 1.8-4.2), pharyngeal (OR = 3.82; 95% CI: 2.0-7.4), and laryngeal carcinomas (OR = 2.34; 95% CI: 1.2-4.7). Significant risk elevations remained for each of the three anatomic sites and for all sites combined even after we purposefully biased the analyses towards the null hypothesis by adjusting the effect of wood stove use only for positive empirical confounders. CONCLUSIONS: The association of use of wood stoves with cancers of the upper aero-digestive tract is genuine and unlikely to result from insufficient control of confounding. Due to its high prevalence, use of wood stoves may be linked to as many as 30% of all cancers occurring in the region. (+info)
Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state.
We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent. (+info)
Time trends in the mortality rates for tobacco- and alcohol-related cancers within the oral cavity and pharynx in Japan, 1950-94.
Mortality data of oral cancer over 40 years in Japan were analyzed to investigate time trends of the disease site-specifically and discuss the relation between these trends and the changing patterns of consumption of tobacco and alcohol beverages. Mortality rates were adjusted to the world standard population. In the males, overall oral cancer (ICD-9: 141-149) mortality rates have increased consistently from the lowest value of 1.25 (per 100,000 per year) in 1956 to 2.40 in 1992. The rates for females were constantly lower than those for males, and formed a modest peak of 0.96 in 1979. Regarding site-specific mortality rates, tongue cancer (141) presented a decreasing trend, while oro/hypopharyngeal (146, 148) and mouth (143-145) cancers showed increasing patterns, particularly in males. When the changing patterns of male truncated rates for ages 35-64 were compared with those of the annual consumption of cigarette and alcohol per capita, the time trend of oro/hypopharyngeal cancer mortality was analogous to cigarette consumption rather than to alcohol consumption, mouth cancer vice versa, and tongue cancer was not related to tobacco or alcohol consumption. The present findings suggest that tobacco and alcohol have different site-specific effects on the development of cancers within the oral cavity and pharynx. (+info)
The prognostic significance of allelic imbalance at key chromosomal loci in oral cancer.
Forty-eight primary oral squamous cell carcinomas (SCC) were screened for allelic imbalance (AI) at 3p24-26, 3p21, 3p13, 8p21-23, 9p21, 9q22 and within the Rb, p53 and DCC tumour suppressor genes. AI was detected at all TNM stages with stage 4 tumours showing significantly more aberrations than stage 1-3. A factional allelic loss (FAL) score was calculated for all tumours and a high score was associated with development of local recurrence (P = 0.033) and reduced survival (P = 0.0006). AI at one or more loci within the 3p24-26, 3p21, 3p13 and 9p21 regions or within the THRB and DCC genes was associated with reduced survival. The hazard ratios for survival analysis revealed that patients with AI at 3p24-26, 3p13 and 9p21 have an approximately 25 times increase in their mortality rate relative to a patient retaining heterozygosity at these loci. AI at specific pairs of loci, D3S686 and D9S171 and involving at least two of D3S1296, DCC and D9S43, was a better predictor of prognosis than the FAL score or TNM stage. These data suggest that it will be possible to develop a molecular staging system which will be a better predict of outcome than conventional clinicopathological features as the molecular events represent fundamental biological characteristics of each tumour. (+info)
Expression of Ricinus communis receptors on epithelial cells in oral carcinomas and oral wounds.
The histological distribution of receptors for Ricinus communis Fraction 1 (RCA1) in oral carcinomas and in oral epithelial cells during wound healing has been studied by use of fluorescein-tagged RCA1. Biopsies from 15 human oral carcinomas and adjacent normal mucosa showed RCA1 receptors at the cell membranes in the basal and spinous layer of the normal epithelium, whereas receptors could not be demonstrated in invading islands of the tumors. In healing oral wounds from eight humans and three monkeys, RCA1 receptors were demonstrated both in normal epithelium adjacent to the wounds and in the epithelial outgrowth from the wound margin. Titrations, however, showed that the epithelial outgrowth reacted more weakly than did the normal adjacent epithelium. These results support previous in vitro studies showing changes in carbohydrate composition of moving normal cells and of malignant cells, a finding that may be of interest in relation to formation of metastases. (+info)
Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers.
Oral cancer is the most common cancer in males and third most common in females in India, the main causative agent being the use of chewing tobacco with or without betel quid (BQ). However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In this study, the prevalence of GSTM1 and GSTT1 null genotypes (GSTM1*2 and GSTT1*2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leukoplakia patients and exfoliated cells from 82 healthy controls both of Indian ethnicity were analysed. GSTM1*1 (active) was present in 83% and GSTT1*1 (active) was present in 78% of all control subjects, while prevalence of GSTM1*2 and GSTT1*2 null genotypes was significantly higher among oral leukoplakia cases. The prevalence of GSTM1*2 in leukoplakia cases was 81.6% compared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (CI), 1047] and GSTT1*2 was 75.5% in the cases versus 22% in controls (OR, 11; 95% CI, 5-22). Combined null genotypes of GSTM1 and GSTT1 prevailed in 60.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive oxygen species, lipid peroxidation products and tobacco-derived carcinogens that have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genotypes of both GSTM1 and GSTT1 increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic population. (+info)
Localization of a putative tumor suppressor gene in the sub-telomeric region of chromosome 8p.
Several regions of chromosome arm 8p are frequently deleted in a variety of human malignancies including those of the prostate, head and neck, lung, and colon, suggesting that there is more than one tumor suppressor gene on this chromosome arm. Both laryngeal and oral squamous cell carcinomas exhibit three distinct and nonoverlapping regions of deletion on 8p. We have further refined the localization of the putative suppressor in 8p23 by using eight microsatellite loci to create a high resolution deletion map of 150 squamous cell carcinomas of the larynx and oral cavity. These new data demonstrate that there are two distinct classes of deletion within this relatively small region of the chromosome and suggest two possible locations for the gene within the D8S264 to D8S1788 interval. We also determined that there is little difference between the allelic loss frequencies of microsatellites mapping near the telomeric ends of other chromosome arms and loci mapping to more centromere proximal regions of the same arm. These data suggest that the high allelic loss frequencies seen at 8p23 loci are not the result of a generalized instability of chromosome ends and are instead consistent with the activation of a specific suppressor gene. (+info)