Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52%), 2p22.3(52%), 1q21.3-q22(54%), 6p21.32(59%), 20p13(61%), 7q34(52% and 72%),8p11.23-p11.22(80%), 8q11.1-q24.4(54%), 9q13-q34.3(54%), 11q23.3-q25(57%); 14q21.3-q31.1(54%); 14q31.3-q32.33(57%), 20p13-p12.3(54%) and 20q11.21-q13.33(52%). The most frequently deleted chromosome region was located on 3q26.1 (54%). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23-p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that were amplified and resulted in consequent over-expression of the MGAM and ADAM9 genes that may be utilized as biological markers for OSCC.
Imatinib mesylate--Gleevec (US), Glivec (worldwide), STI571--is an oral cancer drug that selectively inhibits several protein tyrosine kinases associated with human malignancy. The drug is used for the treatment of chronic myeloid leukemia, malignant gastrointestinal stromal tumors, and some other conditions. Treatment with imatinib is generally well tolerated but not without the risk of adverse effects. The risk of severe adverse events is low. Cutaneous side effects of this drug are common but muco-cutaneous lichenoid eruption with nail changes is very rare. We report a case of lichenoid eruption during imatinib therapy involving the skin, mucous membranes, and nails that cleared in spite of ongoing imatinib therapy.
A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.
The prevalence of oral mucosal lesions in Malaysia was determined by examining a representative sample of 11,707 subjects aged 25 years and above throughout the 14 states over a period of 5 months during 1993/1994. A two-stage stratified random sampling was undertaken. A predetermined number of enumeration blocks, the smallest population unit in the census publication, was selected from each state. With the selected enumeration block, a systematic sample of living quarters was chosen with a random start. The survey instrument included a questionnaire on sociodemographic characteristics and a clinical examination. The clinical examination was carried out by 16 specially trained dental public health officers and the diagnosis calibrated with a final concordance rate of 92%. The age in the sample ranged from 25 to 115 years with a mean of 44.5+/-14.0. The sample comprised 40.2% males and 59.8% females; 55.8% were Malays, 29.4% Chinese, 10.0% Indians and 1.2% other ethnic groups. Oral mucosal lesions were detected in 1131 (9.7%) subjects, 5 (0.04%) had oral cancer, 165 (1.4%) had lesions or conditions that may be precancerous (leukoplakia, erythroplakia, submucous fibrosis and lichen planus) and 187 (1.6%) had betel chewer's mucosa. The prevalence of oral precancer was highest amongst Indians (4.0%) and other Bumiputras (the indigenous people of Sabah and Sarawak) (2.5%) while the lowest prevalence was amongst the Chinese (0.5%).
Proliferating cell nuclear antigen (PCNA) is a well known marker for cell proliferation. It tends to accumulate in the late G1 and S-phase of the cell cycle. A monoclonal antibody (MoAb) against PCNA is now available and it can react with paraffin-embedded specimens. In the present study, PCNA immunohistochemical staining of 36 cases of oral cancer specimens obtained from surgery were investigated. The results showed differing nuclear staining patterns for PCNA in normal, hyperplastic and dysplastic epithelium, early cancer and 3 levels of differentiation for squamous cell carcinoma of the oral cavity. It appears that PCNA can be a useful marker in delineating normal epithelium and hyperplastic epithelium from dysplasia in the oral cavity. The use of PCNA staining may further emphasize the conventional histopathological grading of well-differentiated, moderately-differentiated and poorly-differentiated oral squamous cell carcinoma but is still dependent on basic criteria as observed without immunostaining. PCNA expression for all grades of squamous cell carcinoma are present at the deep, infiltrative margins.