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Objective: CD10 is expressed on the majority of follicle-center lymphomas and Burkitt lymphomas. CD10 has also been shown to be present in a variety of other neoplasms., Design: The aim of this study was a correlation of CD10 and several parameters: age, tumor size, presence of lymph node metastases, clinic stage, histologic grading, presence of local recurrences., Materials and Methods: The tissues of 77 consecutive patients with oral cavity squamous cell carcinoma were evaluated using immunostaining with monoclonal antibody for CD10., Main Outcome Measures: Highly significant correlations were found with the lymph node status, the presence of local recurrences and the histologic grading. The presence of CD10-positive cells was not correlated with the age of patients, tumor size and clinic stage., Results: The results of the present study show that in oral squamous cell carcinoma CD10 positivity is an indicator of worse prognosis. Another strong correlation was found with the presence of local recurrences. Also the histologic grade was significantly correlated with the CD10 positivity., Conclusion: Our results point to the fact that CD10 expression can, perhaps, have an important role in tumor invasion, probably facilitating the occurrence of metastases.

Background: The phosphodiesterases (PDEs) are responsible for the hydrolysis of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), to their corresponding monophosphates with a fundamental role in the transduction of the intracellular signals. At least 11 different enzymatic isoforms have been identified, which are listed according to their specificity or affinity for the substratum, identity of the amino acid sequence, cofactor, and inhibitor sensitivity. Variations in PDE activity have been found in different pathologies, and they have also been correlated to different pathological e/o physiological mechanisms, such as cellular differentiation, apoptosis, and tumor invasivity., Objectives: In this study, we have evaluated cAMP PDE activity in patients with carcinoma of the gingiva, with the purpose of correlating differences in its development and progression. The same enzymatic activity has been used to evaluate differences between patients with lymph node involvement (group N(+)), and patients without lymph node involvement (N(-))., Materials and Methods: The analysis of PDE activity and the cAMP assay was performed by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cAMP was confirmed with the enzyme-linked immunoabsorption assay (EIA)., Results and Conclusions: The differences between control and N(-) groups (P = 0.0433), and between control and N(+) groups (P = 0.0156) were statistically significant. PDE3A was also evaluated immunohistochemically in lymph-node negative and lymph-node positive cases. The differences between the two groups were statistically significant (P = 0.0397).

Background: Cyclic guanosine monophosphate (cGMP) is an essential second messenger metabolized by phosphodiesterases (PDEs)., Objectives: We looked for a possible correlation of PDE activities in human oral squamous cell carcinoma (OSCC) with and without lymph node metastases., Materials and Methods: The analysis of phosphodiesterase activity and the cGMP assay were done by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cGMP was confirmed with the enzyme-linked immunoabsorption assay., Results and Conclusions: cGMP PDE activity was 34.92 +/- 7.17 SD, 12.89 +/- 4.43 SD, and 35.88 +/- 8.76 SD (nmols/mg of protein), respectively, in controls, samples without lymph node involvement (N-), and specimens with lymph node metastases (N+). cGMP values were 1.97 +/- 0.63 SD, 3.30 +/- 1.47 SD, and 3.49 +/- 1.47 SD (nmols/mg of protein). Our data support the hypothesis of a role for cGMP and PDE in the progression of OSCC.

Purpose: Loss of normal p53 is correlated to the progression of several preneoplastic lesions to neoplasms, and overexpression of bcl-2 determines an alteration of programmed cell death. There is an increased awareness of the importance of apoptosis in cancerogenesis, and a strong correlation of Ki-67 with high tumor grade has been reported., Materials and Methods: The aim of our study was to investigate immunohistochemically the expression and relationship of p53, bcl-2, MIB-1, and the apoptotic index (AI) in normal oral epithelium, leukoplakia, dysplasia, and oral squamous cell carcinoma., Results: A strong correlation was found between p53 overexpression and cell proliferation (MIB-1) and the AI. An inverse relationship was found between bcl-2 expression and MIB-1 and AI. A significant inverse relationship was found between p53 and bcl-2. A good positive correlation was present between AI and MIB-1 expression., Conclusions: Apoptosis could be important to help to understand oral carcinogenesis., (Copyright 2002 American Association of Oral and Maxillofacial Surgeons)

Background: Carcinogenesis is thought to be dependent on neovascularization. Vascular endothelial growth factor (VEGF) is a glycoprotein that has the capability of increasing vascular proliferation and permeability. VEGF has been found to be expressed in several different types of tumours and it may contribute to the progression of malignant tumours. Increased microvessel density (MVD) has been described in oral squamous cell carcinoma (OSCC) and seems to be related to patient prognosis., Materials and Methods: Fifty-two cases of OSCC were evaluated in the present study. Immunostaining for VEGF and Factor-VIII was performed. The MVD was evaluated in G1, G2 and G3 tumours., Results: The differences between these 3 groups were statistically significant (p = 0.0331). MVD was also evaluated in lymph-node negative and lymph-node positive cases: the differences between these two groups were statistically significant (p < 0.0001). VEGF expression was evaluated in G1, G2 and G3 tumours. The differences between the 3 groups were not statistically significant (p = 0.289), even if an increasing trend in the VEGF positivity was evident from G1 to G3. The difference of VEGF expression between tumours with and without lymph node metastases was not significant (p = 0.196). No correlation was present between intensity of VEGF positivity and histological grading or lymph-node status and between VEGF and MVD., Conclusion: Our data showed that MVD was correlated with grading and lymph-node status, while no similar correlation was found for VEGF.

A large number of oral cancer patients show poor or partial response to chemotherapy and the mechanisms are poorly understood. At present, an MDR-1 product, the P-170 glycoprotein, is the best known of the P-170 family and is involved in resistance to natural product-based chemotherapeutics, including taxanes, anthracyclines, vinca alkaloids, podophyllotoxins and camptothecins. Although several reports suggest that P-170 is clinically relevant in haematological malignancies, its role in solid tumours is not well understood. Its overexpression has been found to be correlated with the poor outcome observed in patients treated with chemotherapy and presenting drug resistance. The aim of this study was to detect the protein expression patterns of MDR-1 product by immunohistochemistry in formalin-fixed-paraffin-embedded tissues. For these reasons, 30 oral SCC and 6 healthy oral mucosa specimens were tested with anti-P-170 antibodies using standard streptavidin-biotin-peroxide technique. Immunohistochemistry demonstrated that 4 cases (66.6%) of normal oral mucosa and 24 cases (80%) of oral SCC showed positivity. Four cases (13.4%) showed strong positivity in tumour areas and complete negativity in normal epithelial cells adjacent to the tumour. No staining was observed in stromal structures, with the exception of the lymphocytic compartment that showed a strong staining as reported in literature for CD56+ and CD8+ cells. Four G1 tumours (33%) and 2 G3 tumour (33%) showed strong positivity in areas with a higher degree of differentiation. P-170 positivity in normal epithelial cells of smoker patients, in differentiated area of neoplasia and negativity or zonal positivity in undifferentiated area of tumour suggested that activation of the MDR-1 gene or selection of intrinsically multidrug resistance neoplastic cells may occur at early stages of tumorigenesis of oral cancers, before the real evidence of cellular transformation. Thus the contact with possible chemical carcinogens, such as those of tobacco smoke, may induce activation of MDR-1 gene. This study was conducted only on untreated carcinomas so for this reason it cannot indicate the real incidence of acquired multidrug resistance. The data of MDR-1 product expression by immunohistochemistry in oral SCC might suggest that an overexpression of this protein could constitute a hallmark of potential more aggressive phenotype for this type of neoplasia and a rapid method for pre-screening tumours for a constitutive multidrug resistance in order to orientate the cancer treatment.

Background: A large number of oral cancer patients shows poor or partial response to chemotherapy and the mechanisms are poorly understood. Glutathione-S-transferase (GST) is one of the molecules involved in resistance to natural product-based chemotherapeutics. It is an enzyme able to conjugate several substances (metabolites, drugs) to reduct glutathione. Today several isoenzymes of GST are known: GST-alpha, GST-mu, GST-pi, GST-theta. Over-expression of glutathione S-transferase-pi class isozyme is often associated with malignant transformation. Several studies reported that GST-pi staining patterns and their distribution may be helpful in identifying high-risk oral lesions. However, GST is surely involved in resistance to alchilant agents., Objective: To verify the possibility of implication of GST in oral cancerogenesis and in natural chemioresistance, the authors examined the protein expression patterns by immunohistochemistry in paraffin-embedded specimens of primary untreated oral cancers (OSCC)., Methods: GST-a and GST-pi expression in 17 cases of OSCC at different degree of cellular differentiation have been evaluated by immunohistochemistry., Results: The GST-pi expression in primary tumours predominantly varied from mild to moderate levels. The GST-a expression was often quite similar to GST-pi expression with a few exceptions., Conclusions: Expression of GST enzymes is an important signal for multidrug resistance: positive staining for both GST-pi and GST-a could constitute a hallmark of chemoresistant groups of OSSC.