Miguel Angel Gonzalez-Moles

Oral lichen planus: controversies surrounding malignant transformation

Studies of the malignant potential of oral lichen planus (OLP) have been hampered by inconsistencies in the diagnostic criteria used for OLP, the criteria adopted to identify a true case of malignant transformation in OLP, the risk factors for malignant transformation and the optimum management of patients to ensure the early diagnosis of transformation. Consensus remains elusive, and leading workers in this field have recently published conflicting reports on the malignant potential of OLP and on the important question of the advisability of excluding patients with epithelial dysplasia or a tobacco habit from studies on this issue. The present review outlines these debates and proposes a possible a molecular basis for the malignant transformation in this disease.

Importance of tumour thickness measurement in prognosis of tongue cancer

Eighty-one patients who underwent surgery for cancer of the tongue were retrospectively studied to evaluate the influence on survival of some clinical and pathologic parameters. These parameters and data on the patients current status were gathered by the study of tissue sections, using haematoxylin-eosin staining, and from medical records. The 5-year survival rate was 68.5%. Univariate analysis showed that the parameters influencing survival were: T (P<0.01), pathologic T (P<0.01), N (P<0.05), pathologic N (P<0.05), extracapsular nodal spread (P<0.05), locoregional recurrence (P<0.01), and tumour thickness (P<0.05). Multivariate analysis showed that tumour thickness had the greatest influence on survival. Patients with tumour thickness of < or = 3 mm had a 5-year survival of 85.7%, significantly greater (P<0.05) than the rates of 58.3 and 57% for patients with tumour thickness of 4-7 mm and >7 mm, respectively. Wider studies are required to unify criteria for the measurement of this important prognostic parameter.

A role for substance P in cancer promotion and progression: a mechanism to counteract intracellular death signals following oncogene activation or DNA damage.

In the present review we discuss a central role for substance P (SP) in carcinogenesis. We suggest that one mechanism to induce mitogenesis of tumor cells is the activation of neurokinin-1 receptor (NK1R) through SP, linking cancer promotion and progression to a neurokinin-mediated environment. After reviewing the role of both SP and its receptor NK1R in normal and neoplastic cells we propose the use of neurokinin-1 receptor antagonists as a novel and promising approach for treating patients with cancer.

Oral health in the elderly patient and its impact on general well-being: a nonsystematic review.

Data on the oral health of the elderly depict a worrying situation, with an elevated prevalence of caries and moderate periodontal disease, frequent edentulism, and numerous cases of dry mouth and oral cancer. There is wide evidence that periodontitis is a risk factor for certain systemic diseases, and impaired oral health has been associated with mastication and nutritional problems, especially among the elderly, with highly negative effects on their quality of life. In this nonsystematic review, the authors discuss the importance of evaluating the oral health of the geriatric population in a comprehensive manner, beyond simple clinical assessments.

Evaluation of the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lysozyme and lactoferrin in elderly patients with dry mouth – a pilot study

OBJECTIVES To evaluate the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lactoferrin and lysozyme, in a sample of elderly individuals with dry mouth. MATERIAL AND METHODS Twenty elderly institutionalised subjects with dry mouth and with a certain degree of independence for daily life activities were included in this pilot study. A randomised, double blind and cross-over design was used. The study variables comprised subjective dry mouth sensation, the severity of discomfort assessed by means of a visual analogical scale (VAS), the Oral Health Impact Profile (OHIP), the presence of signs and symptoms of dry mouth, sialometry and Candida albicans culture. All the variables were recorded before and after each of the two periods of the study. RESULTS The 20 selected subjects we made up of 16 women and four men, with a mean age of 81.3 years. Improvement was observed on analysing the data between the first and second intervention period in terms of the OHIP values, the presence of dry mouth, and the need to drink fluids to swallow. However, the improvement in certain variables before and after treatment did not take a positive course in all cases, and some subjects even improved with placebo. CONCLUSIONS The evaluated mouthwash and oral gel improved some subjective and clinical aspects in elderly individuals with dry mouth, though a placebo effect cannot be entirely discarded.

Expression of substance P and neurokinin‐1‐receptor in laryngeal cancer: linking chronic inflammation to cancer promotion and progression

Sir: Substance P (SP) is an undecapeptide that belongs to the tachykinin family and has been implicated in a myriad of physiological processes. In recent years it has been demonstrated that SP acts through the neurokinin-1 receptor (NK1R) as a mitogen on several human cancer cell lines. It seems that the SP ⁄ NK1R system could play an important role in the development of cancer, as SP may be a universal mitogen in NK1R-expressing tumour cell types. However, in their pioneer work on SP receptors in human primary neoplasms, Henning and coworkers did not study squamous cell carcinoma. Although NK1R has been recently described in the Hep-2 laryngeal carcinoma cell line, this is, to our knowledge, the first study of SP and NK1R expression in laryngeal cancer. We reviewed 114 consecutive cases of laryngeal carcinoma treated surgically from the Department of Otolaryngology. Surgical procedure, site of the primary tumour and TNM staging were recorded. None of the patients had received radiotherapy and ⁄ or chemotherapy prior to surgery. Of the 114 patients, 78 (68%) remained disease free at the end of the follow-up period (average 40 months, range 12–96 months). Tumour differentiation was recorded according to World Health Organization criteria. Cases were also carefully staged to conform to the American Joint Committee on Cancer Staging and End Results Reporting. The presence of adjacent non-neoplastic epithelium was also recorded. Laryngeal non-neoplastic epithelium consisted of pseudostratified squamous epithelium. The histological and immunohistochemical analyses were performed without any knowledge of the clinical stage, treatment or further course of the disease. For the detection of SP and NK1R we used monoclonal antibodies against SP (Sigma, St Louis, MO, USA) and NK1R (Sigma-Aldrich, Madrid, Spain), as previously described. The number of tumour cells showing immunoreactivity (brown staining) and its location were noted. Groups were formed according to the percentage of positive cells (0–24, 25–49, 50–74 and >75%). SP and NK1R expression in non-neoplastic epithelium adjacent to tumour was also recorded in the same way. The presence of basal and suprabasal expression was also recorded. The relationship between SP and NK1R expression and clinical and pathological parameters was determined by v analysis and Fisher’s exact test. All P-values corresponded to two-sided significance testing. The relationship of survival to the expression of proteins was examined using the Kaplan–Meyer method and multivariate survival analysis. SP was immunoreactive in 93 out of 97 samples of non-neoplastic epithelium close to the tumour. Reactivity was found mainly in the basal layers (Figure 1A), with >75% reactive cells. Out of 114 cases, 111 studied showed homogeneous SP expression, with 90 tumours scored as ++++ (Figure 1B). Only three cases were classified as negative. Six were considered +, seven ++ and eight +++. All 17 metastases studied were immunoreactive for SP (Figure1C). All cases showed the same expression as the primary tumour (+++ ⁄ ++++). Out of 97 cases, the basal layers were reactive for NK1R in 72 (Figure 2A). Ninety of 97 samples were positive for NK1R, with >25% of tumour cells reactive (Figure 2B). Reactivity was detected both in the membrane and cytoplasm. We did not find any relationship between expression in primary carcinomas and clinicopathological parameters or survival (data not shown). All cases of metastases (17 out of 17) were found to express NK1R in most tumour cells (+++ ⁄ ++++) (Figure 2C). SP participates in acute inflammation and activates key proteins involved in mitogenic pathways, such as mitogen-activated protein kinases (MAPKs), stimulating DNA synthesis. We found both membranous and cytoplasmic SP immunoreactivity, which can be explained on the basis of NK1R internalization. Cytoplasmic reactivity has also been reported in lymphocytes of children who go on to develop acute lymphoblastic leukaemia. The ubiquitous presence of SP in laryngeal tumours may represent a common mechanism of tumour progression. In fact, an intriguing question is why some lymphocytes in normal mucosa express SP, whereas those in metastatic lymph nodes do not. We propose a SP link between chronic mucosal inflammation and cancer, with submucosal lymphocytes secreting SP, as has been described in neoplastic lymphocytes. In addition, it has been demonstrated that the activation of NK1R by SP or SP analogues induces

Suprabasal expression of Ki-67 antigen as a marker for the presence and severity of oral epithelial dysplasia.

Suprabasal expression of Ki‐67 is assessed as a marker for oral dysplasia. The study involved non‐neoplastic epithelium adjacent to 74 oral squamous cell carcinomas.

Epstein-Barr virus latent membrane protein-1 (LMP-1) expression in oral squamous cell carcinoma.

Objectives Epstein‐Barr virus (EBV) is frequently associated with malignant cell transformation through the action of the oncoprotein latent membrane protein‐1 (LMP‐1). The present study aimed to determine the presence of EBV in oral squamous cell carcinomas (OSCCs) and the expression of LMP‐1 in neoplastic cells of EBV‐positive OSCCs.

Analysis of Ki-67 expression in oral squamous cell carcinoma: Why Ki-67 is not a prognostic indicator

OBJECTIVES To analyze the prognostic value of Ki-67 in oral cancer and its relationship with Ki-67 expression in precancerous epithelium. MATERIAL AND METHODS We studied 79 tumors from 65 patients. Immunohistochemistry study with Mib-1 monoclonal antibody was used to detect Ki-67 expression in tumor tissue and adjacent non-tumor tissue. The influence of different variables on survival was studied with univariate and multivariate analyses. RESULTS Ki-67 expression was significantly higher in well-differentiated versus poorly-differentiated carcinomas. The survival time of these patients was affected by the clinical presentation, T, N, stage, and surgical treatment. Ki-67 expression had no impact on survival. An association was found between the parabasal expression of Ki-67 in adjacent non-tumor epithelium and Ki-67 expression in the tumor. CONCLUSIONS Ki-67 lacks prognostic value, probably because it is a marker of the total fraction of proliferating cells, corresponding not only to cells in constant proliferation but also to proliferating cells destined for terminal differentiation.

Methylation in oral cancer and pre-cancerous lesions (Review)

There is considerable interest in the analysis of epigenetic alterations in cancer, including oral cancer and pre-cancerous lesions. These processes affect or inactivate the functions of genes without altering their structure or sequence. One example is the methylation of the promoter region of some genes involved in cell cycle control. Knowledge of methylation patterns is very important for understanding the expression of genes in normal and pathological situations. This review provides an update on research into this issue in oral cancer and pre-cancerous lesions. A greater understanding of this epigenetic alteration could not only assist the diagnosis and prognosis of oral cancer but could also open up novel therapeutic approaches. The presence of methylation in specific tumour suppressor genes could modify their function and alter cell cycle control, so the patients could have an increased risk of developing cancer and also a higher degree of malignancy. The most frequently and extensively studied methylated genes in oral premalignant lesions are p16, MGMT, RARβ2, E-cadherin and DAP-kinase.