Apoptosis is a genetically determined process playing an active role in tissue size regulation, morphogenesis and removing damaged cells that could be potentially dangerous for their host. Several agents involved in apoptosis regulation, such as the bcl-2 family components, act as oncogenes and are involved in oral carcinogenesis. Aim of this study is to explore bcl-2 immunoreactivity in oral cancers and to assess its potential clinico-pathological implications. Ninety oral squamous cell carcinoma and 10 normal mucosal formalin-fixed, paraffin-embedded samples were analysed for bcl-2 expression by immunohistochemistry. Normal oral mucosa showed a cytoplasmic pattern of bcl-2 immunoreactivity in the basal cell layers. Seventy-four cases of carcinoma (83%) showed no immunoreactivity, at variance with 16 cases (17%) manifesting consistent cytoplasmic positivity. Overall, the peripheral cells of differentiating epithelial tumour islands were intensely stained, with decreasing immunoreactivity toward the centre of the neoplastic nests. Fully keratinised tumour cells showed inconspicuous or absent bcl-2 immunoreactivity. No statistically significant correlations could be demonstrated between bcl-2 immunoreactivity and the sex of the patients, tumour size and with the occurrence of lymph node metastases. Though a direct correlation was found between bcl-2 immunoreactivity and increasing tumour stage, this did not reach statistical significance. Furthermore, G1 and G3 tumours displayed higher percentages of bcl-2-positive cells in comparison with G2 neoplasms and the different distribution of bcl-2 immunoreactivity in G2 and G3 was statistically significant (p<0.05). Finally, patients with absent or low (scores 0 and 1) bcl-2 immunoreactive tumours manifested poorer overall survival rates in comparison with patients with moderate or high (scores 2 and 3) bcl-2 immunoreactive tumours but the difference was not statistically significant. In normal oral mucosa bcl-2 protein is selectively present in the basal cell layers and possibly participates in the control of the terminal keratinocytes differentiation. The study of bcl-2 immunoreactivity possibly may be useful for better characterising and predicting the prognosis of oral SCC but cooperative studies are needed to assess its applications in the clinical practice.

Aged↗

PubMedDate not supplied

The NM23 gene and its expression in oral squamous cell carcinoma.

The murine nm23, a putative metastasis suppressor, has three human homologues, NM23-H1, -H2, and -H3b. Several reports have suggested a low metastatic potential for neoplasms with a high expression of NM23-H1 gene, while other studies have not shown this relationship. These apparent differences in the role of NM23 in metastasis suppression might be explained by unability to discriminate between the expression of the two genes NM23-H1 and NM23-H2. The NM23-H2 product is not related to tumor progression and metastasis suppression. Two studies on human oral squamous cell carcinoma (OSCC) have been reported, both showing the NM23 product to be a metastasis suppressor factor. However, none of these two studies distinguished NM23-H1 from NM23-H2. The aim of this study was to detect the protein expression pattern of NM23-H1 product in 24 OSCCs by immunohistochemistry in paraffin-embedded tissues using a monoclonal antibody non-cross-reactive with NM23-H2. The NM23-H1 positive group showed lower frequency of lymph node metastasis, and a better grading than the NM23-H1 negative group supporting the role of NM23-H1 as metastasis suppressor factor which may be useful for predicting tumor metastasis in OSCC.

Aged↗

PubMedDate not supplied

Immunocytochemical detection of hMSH2 and hMLH1 expression in oral SCC.

BACKGROUND: The loss of DNA mismatch repair system was reported in hereditary non-poliposis colon cancer and in other tumours. The aim of this study was to detect the protein expression pattern of hMSH2 and hMLH1 in oral squamous cell carcinoma (SCC) by immunohistochemistry in paraffin-embedded tissues. MATERIALS AND METHODS: 5 specimens, obtained from healthy oral mucosa, and 20 from oral SCC were tested with anti-hMSH2 and anti-hMLH1 monoclonal antibodies. RESULTS: Six cases (30%) showed nuclear positivity in differentiated areas (G1) and cytoplasmic positivity in areas with a lower degree of differentiation, four cases (20%) showed only cytoplasmic positivity, and only one (5%) no staining. One case of oral SCC (5%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity; six cases (30%) showed nuclear positivity in differentiated areas (G1) and cytoplasmic positivity in areas with a lower degree of differentiation, three cases (15%) showed only cytoplasmic positivity. CONCLUSIONS: These data suggest that examination of hMSH2 and hMLH1 protein expression by immunohistochemistry is important in oral SCC. The analysis of mismatches expression in these cases of oral SCC might suggest that an absent nuclear staining for both hMSH2 and hML1 could constitute a hallmark of potential phenotype mutator for this type of neoplasia.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Beta- and gamma-catenin expression in oral squamous cell carcinomas.

Cell-cell adhesion is mediated by cadherins (integral membrane proteins) which form a complex with catenins (cytoplasmatic proteins). Down-regulation of cadherins and more recently of catenins has frequently been detected in many types of human carcinomas, in which it has been associated to tumor progression. While E-cadherin expression has been extensively studied in many forms of human cancers, including oral SCC, less is known about the expression levels of catenins in oral SCCs. The objective of this study was to evaluate the role of these proteins in the carcinogenetic process of the oral cavity. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 30 cases of intraoral squamous cell carcinomas at different degree of cellular differentiation. As already reported for E-cadherin, the beta- and gamma-catenin expression showed an inverse relationship with the degree of differentiation, being the membranous expression of both catenins homogeneously reduced in less differentiated oral squamous cell carcinomas (grade 3). More interestingly, a decreased expression of these molecules was also found at the invasive front of grade 2 and sometimes of grade 1 carcinomas, thus suggesting a more aggressive biological behavior of these cancer cells. An absent staining for both beta- and gamma-catenins could constitute a hallmark of aggressive biological behavior even in tumor still well or moderately differentiated, at least in the peripheral invading front constituted by less differentiated tumor cells.

Adult↗

PubMedDate not supplied

Immunocytochemical detection of hMSH2 and hMLH1 expression in oral melanoma.

BACKGROUND: The DNA mismatch repair system (MMR) plays an important role in the maintenance of genomic stability. To date few studies have been performed on hMSH2 and hMLH1 expression and melanoma of the head and neck region. A study of two cases revealed no mutations of the mismatch repair genes hMSH2 and hMLH1. MATERIALS AND METHODS: To verify the possibility of implication of hMSH2 and hMLH1 alterations in melanocytic cancerogenesis, the authors examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in 9 paraffin-embedded oral melanoma. RESULTS: One case (11%) showed nuclear positivity for hMSH2, 3 cases (33%) showed cytoplasmic positivity, and five cases (55%) showed no staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Four cases (44%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Two cases (22%) showed nuclear positivity, and three cases (33%) showed cytoplasmic positivity. CONCLUSIONS: The analysis of mismatch repair genes can be a new molecular diagnostic tools for the detection of patients at high risk of developing melanoma and other neoplasia, or metastasis and recurrences.

Adaptor Proteins, Signal Transducing↗