Quality of Life vs. Supportive Care Needs for Oral Cancer Caregivers: Are They Related?

Caregivers providing care for their family members with oral cancer usually endure the caregiving burden in silence, which affects their quality of life and necessitates the need for supportive care. The aim of this study is to determine the relationship between the quality of life (QOL) of oral cancer caregivers and their supportive care needs (SCN) in Malaysia. The Malaysian versions of the Caregiver Oncology Quality of Life Questionnaire (M-CarGOQoL) and the Comprehensive Needs Assessment Tool for Cancer Caregivers (M-CNAT-C) were self-administered by 56 family caregivers of oral cancer patients from five tertiary hospitals throughout Peninsular Malaysia and Sarawak between October and December 2021. Correlation and multiple regression analyses were employed, and the significance level was set at p < 0.05. The mean score for the QOL of caregivers was 76.16 ± 16.01, with the lowest scores in the psychological well-being (64.87 ± 30.12) and self-esteem (68.64 ± 28.29) domains. The mean score for SCN of caregivers was 36.42 ± 24.16, with the highest scores in the healthcare staff (58.44 ± 33.80) and information (55.35 ± 29.98) domains. The correlation between QOL and SCN was moderately inversed, (r(54) = 0.58, p < 0.01). There was a significant effect of caregiving duration (<3 h/day versus >3 h/day) on the combined dependent variables (QOL and SCN), F(2, 53) = 5.006, p < 0.01, partial η2 = 0.16. QOL and caregiving duration accounted for a significant 43% of SCN, R2 = 0.43, adjusted R2 = 0.41, F(2, 53) = 20.32, p < 0.01. In conclusion, oral cancer caregivers with poorer QOL have higher SCN. It is recommended that oral cancer caregivers be recognized by healthcare providers in order to deliver holistic patient care.

High referral accuracy for oral cancers and oral potentially malignant disorders using telemedicine.

OBJECTIVE: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral. SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions. RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®. CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.

Overexpression of gamma glutamyl hydrolase predicts extranodal extension in squamous cell carcinoma of the oral cavity.

OBJECTIVE: Extranodal extension (ENE) is an important prognostic factor in oral squamous cell carcinoma (OSCC). However, ENE is only confirmed postoperatively by histologic assessment of the lymph nodes after neck dissection. Accurate identification of ENE preoperatively would help in management of OSCC. STUDY DESIGN: We determined the expression of molecular markers gamma glutamyl hydrolase (GGH), cyclin-dependent kinase inhibitor-3 (CDKN3), and chromobox homolog-7 (CBX7) using immunohistochemistry in OSCC clinical samples (n = 35). The intensity of staining was scored using a semiquantitative index (HSCORE). The association between clinicopathologic parameters and expression of molecular markers with ENE status was analyzed using chi-square test. RESULTS: The number of positive nodes and the highest anatomic level of nodal involvement significantly correlated with ENE (P < .05). High GGH expression was significantly associated with ENE (P < .05), with an increased risk for ENE (odds ratio [OR] 9.9, 95% CI 1.08-91.47, P = .04), whereas no significant association was seen for CDKN3 and CBX7 expression with ENE. However, a trend toward significance was observed with a high level of CDKN3 and a low level of CBX7 expression with ENE. CONCLUSIONS: Gamma glutamyl hydrolase offers potential as a predictor for ENE in OSCC, whereas the role of CDKN3 and CBX7 need to be validated in a larger sample.

Prognostic Abilities of Pre- and Post-Treatment Inflammatory Markers in Oral Squamous Cell Carcinoma: Stepwise Modelling.

Background and Objectives: Studies examining the importance of inflammatory markers before treatment as prognosticators of OSCC are available, but information on post-therapy inflammatory markers and their prognostic significance is limited. This study aimed to evaluate the prognostic abilities of pre- and post-treatment inflammatory markers in patients with OSCC. Materials and Methods: In this retrospective analysis, information on 151 OSCC patients' socio-demographic, clinico-pathological, recurrence, metastasis, and survival data were gathered from clinical records. A multivariable Cox proportional hazards regression (stepwise model) was conducted to identify the prognostic predictors of OS and DFS. The multivariable models' performances were evaluated using Harrell's concordance statistics. Results: For OS, high pre-treatment LMR (HR 3.06, 95%CI 1.56, 5.99), and high post-treatment PLC (HR 3.35, 95%CI 1.71, 6.54) and PLR (HR 5.26, 95%CI 2.62, 10.58) were indicative of a poor prognosis. For DFS, high pre-treatment SII (HR 2.59, 95%CI 1.50, 4.48) and high post-treatment PLC (HR 1.92, 95%CI 1.11, 3.32) and PLR (HR 3.44, 95%CI 1.98, 5.07) were associated with increased mortality. The fitness of the OS and DFS stepwise Cox regression models were proven with a time-dependent AUC of 0.8787 and 0.8502, respectively. Conclusions: High pre-treatment levels of LMR and SII and high post-treatment levels of PLC and PLR are independent predictors of a poor prognosis for patients with OSCC.

Do Clear Cell Changes in Oral Squamous Cell Carcinoma Warrant It Being Recognised as a Variant?

Histological variants of oral squamous cell carcinoma (OSCC) include verrucous, basaloid, spindle cell, adenosquamous, papillary, and acantholytic types. Clear-cell changes in OSCC are rare. We report a case of a 65-year-old male Chinese patient who presented with a swelling in the lower-left mandible for three weeks, causing ill-fitting of his lower denture and an ulcer on the floor of the mouth. Histologically, the lesion showed a dense proliferation of malignant tumor cells arranged in islands and sheets consisting of squamoid cells intermixed with signet ring-shaped clear cells. The clear cells were negative for mucicarmine, periodic acid Schiff (PAS), periodic acid Schiff-diastase (PAS-D), and alcian blue (AB). Immunohistochemistry showed the tumor cells were immuno-positive for cytokeratin (CK) and p63, but CK7, CK20, and S100 were immuno-negative. Therefore, a metastatic tumor in the oral cavity was suggested. However, the CT scan did not show any primary tumors in other sites. Histopathologically, the surgical specimen showed signet-ring-shaped clear cells in the stroma with squamoid cells invading the underlying connective tissue from the surface epithelium, suggesting a diagnosis of clear cell changes in OSCC. Follow-up showed recurrent OSCC at the base of the tongue with lymph node metastasis and distant metastasis in the lung. Only a few cases of clear-cell changes have been reported, with most having a poor prognosis. This case report adds one more case of clear cell changes in the OSCC with a poor prognosis. We reviewed the literature to understand their clinical behavior. Due to the rarity of its (clear cell changes) occurrence, further research is required in order to obtain a better understanding of the clinical behavior and prognosis of these clear cell changes seen in OSCC.

Psychometric properties of the Malay Fonseca Anamnestic Index for temporomandibular disorders.

OBJECTIVE: This study translated/cross-culturally adapted the Fonseca Anamnestic Index (FAI) for temporomandibular disorders (TMDs) into Malay and psychometrically tested the Malay-FAI (FAI-M). METHODS: The FAI-M was created according to international guidelines. Internal consistency/test-retest reliability were assessed with Cronbach's alpha/intra-class correlation (ICC) coefficients. Construct and convergent validity were appraised by relating the FAI-M to the Global Oral Health (GOH) questionnaire and Short-form Oral Health Impact Profile (S-OHIP) using Kruskal-Wallis and Spearman's rho correlation (α = 0.05). RESULTS: Of the 243 participants enrolled, 54.7% (n = 133) had no TMDs, while TMDs were present in 45.3% (n = 110). The FAI-M presented very good internal consistency (α = 0.90) and test-retest reliability (ICC = 0.99). Theoretically predicted FAI-M score patterns matched the GOH categories, and strong correlations were discerned between FAI-M and S-OHIP (rs = 0.71). CONCLUSION: The FAI-M exhibited good psychometric properties and can be applied in Malay-speaking populations.

C-kit Expression in Oral Leukoplakia.

Oral leukoplakia is the most common potentially malignant oral disorder. Oral leukoplakia's malignant potential is independent of the histopathological grade, and the malignant transformation rate varies greatly from 3% to 50% even in the case of severe epithelial dysplasia. Ethnic & environmental variables may contribute to this variation. C-kit immunohistochemistry was performed on 15 oral leukoplakia (OL), two oral squamous cell carcinoma (OSCC), and two dentigerous cysts (DC). The objective of this study was to evaluate the c-kit expression in oral leukoplakia. The use of various immunohistochemical markers to differentiate between OLs with a high and low risk of malignant transformation has been investigated. Only four OL exhibited a faint cytoplasmic expression in basal cells. Whereas, OSCC and DC were devoid of c-kit expression. Thus, this may not be a unique marker for identifying OL at high-risk. Further research with larger sample size is required. Key Words: CD 117, Disease progression, Oral dysplasia, Oral leukoplakia, Risk prediction.

DNA Vaccines Targeting Novel Cancer-Associated Antigens Frequently Expressed in Head and Neck Cancer Enhance the Efficacy of Checkpoint Inhibitor.

HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner.

Translation and Adaptation of the Diagnostic Criteria for Temporomandibular Disorders into the Malay Language: Psychometric Evaluation of Contents.

AIMS: To develop the Malay DC/TMD through a formal cross-cultural adaptation (CCA) process for use in non-English speaking populations and to determine the reliability and validity of the Malay Graded Chronic Pain Scale (M-GCPS) and Malay Jaw Functional Limitation Scale (M-JFLS). METHODS: The English DC/TMD was translated into the Malay language using the forward-backward translation procedures specified in the INfORM guideline. The initial Malay instrument was pre-tested, and any discrepancies were identified and reconciled before producing the final Malay DC/TMD. Psychometric properties of the M-GCPS and M-JFLS were evaluated using a convenience sample of 252 subjects and were assessed using internal consistency and test-retest reliability, as well as face, content, concurrent, and construct validity testing. Internal consistency was assessed using Cronbach's alpha, while test-retest reliability was examined using intraclass correlation coefficient (ICC). Concurrent and construct validity of both domains were performed using Spearman ρ correlation test. In addition, construct and discriminant validity were appraised using Kruskal-Wallis and Mann-Whitney U tests, respectively. RESULTS: Cronbach's alpha values for the M-GCPS and M-JFLS were 0.95 and 0.97, respectively. The ICC was 0.98 for the M-GCPS and 0.99 for M-JFLS. The majority of the tested associations for both domains were found to be statistically significant, with good positive correlations. CONCLUSION: The M-GCPS and M-JFLS were found to be reproducible and valid. The Malay DC/TMD shows potential for use among Malay-speaking adults.

Can post-treatment oral cancer patients' concerns reflect their cancer characteristics, HRQoL, psychological distress level and satisfaction with consultation?

BACKGROUND: Oral cancer and its treatment impact patients' post-treatment outcomes, challenging clinicians to manage them optimally. Addressing patients' concerns is central to holistic patient-centred care. OBJECTIVES: This study aimed to determine post-treatment oral cancer patients' concerns and its relationship with patients' clinical characteristics, health-related quality of life (HRQoL), psychological distress and patient satisfaction with the follow-up consultation. METHODS: A total of 85 oral cancer patients were recruited from a three-armed pragmatic RCT study on the patient concerns inventory for head and neck cancer (PCI-H&N), which was conducted at six hospital-based oral maxillofacial specialist clinics throughout Malaysia. Malaysians aged 18 years and above and on follow-ups from 1 month to 5 years or more were eligible. Patients completed the PCI-H&N, functional assessment of cancer therapy -H&N v4.0 and Distress Thermometer at pre-consultation and satisfaction questionnaire at post-consultation. The data were analysed descriptively; multiple linear regression and multivariate logistic regression analyses were used to determine possible predictors of patients' HRQoL and psychological distress. RESULTS: 'Recurrence or fear of cancer coming back' (31.8%) was most frequently selected. 43.5% of patients selected ≥4 concerns. A significantly high number of concerns were associated with patients of '1-month to 1-year post-treatment' (n = 84%; p = 0.001). A significant association existed between 'time after treatment completed' and patients' concerns of 'chewing/eating', 'mouth opening', 'swelling', 'weight', 'ability to perform', 'cancer treatment' and 'supplement/diet-related'. 'Chewing/eating' was predicted for low HRQoL (p < 0.0001) followed by 'appearance' and 'ability to perform recreation activities' (personal functions domain). Patients with high psychological distress levels were 14 times more likely to select 'ability to perform recreation activities' and seven times more likely to select 'feeling depressed'. No significant association was identified between patients' concerns and patients' satisfaction with the consultation. CONCLUSION: Routine follow-up consultations should incorporate the PCI-H&N prompt list to enhance patient-centred care approach as the type and number of patients' concerns are shown to reflect their HRQoL and psychological distress.TRIAL REGISTRATION: NMRR-18-3624-45010 (IIR).

Inflammatory Responses in Oro-Maxillofacial Region Expanded Using Anisotropic Hydrogel Tissue Expander.

OBJECTIVE: Reconstruction of oral and facial defects often necessitate replacement of missing soft tissue. The purpose of tissue expanders is to grow healthy supplementary tissue under a controlled force. This study investigates the inflammatory responses associated with the force generated from the use of anisotropic hydrogel tissue expanders. METHODS: Sprague Dawley rats (n = 7, body weight = 300 g ± 50 g) were grouped randomly into two groups-control (n = 3) and expanded (n = 4). Anisotropic hydrogel tissue expanders were inserted into the frontal maxillofacial region of the rats in the expanded group. The rats were sacrificed, and skin samples were harvested, fixed in formalin, and embedded in paraffin wax for histological investigation. Hematoxylin and eosin staining was performed to detect histological changes between the two groups and to investigate the inflammatory response in the expanded samples. Three inflammatory markers, namely interleukin (IL)-1α, IL-6, and tumor necrosis factor-α (TNF-α), were analyzed by immunohistochemistry. RESULT: IL-1-α expression was only observed in the expanded tissue samples compared to the controls. In contrast, there was no significant difference in IL-6, and TNF-α production. Histological analysis showed the absence of inflammatory response in expanded tissues, and a negative non-significant correlation (Spearman's correlation coefficient) between IL-1-α immune-positive cells and the inflammatory cells (r = -0.500). In conclusion, tissues that are expanded and stabilized using an anisotropic self-inflating hydrogel tissue expander might be useful for tissue replacement and engraftment as the expanded tissue does not show any sign of inflammatory responses. Detection of IL-1-α in the expanded tissues warrants further investigation for its involvement without any visible inflammatory response.

Analysis of octamer-binding transcription factor-4 expression in oral leukoplakia.

BACKGROUND: Oral potentially malignant disorders have a risk for malignant transformation but are difficult to reliably identify and predict which patients are at the risk for malignant transformation. OCT4 has been hypothesized to play a key oncogenic driver in a variety of solid tumors. A deeper understanding of the aberrant molecular pathways which lead to carcinogenesis needs to be identified by the potential markers. AIMS: To assess the OCT4 stemness factor in oral leukoplakia for its potential risk to malignant transformation. SETTINGS AND DESIGN: 20 cases of oral leukoplakia were obtained from archives at Oral Cancer Research & Coordinating center (OCRCC) Malaysia Subjects and Methods: 20 cases of oral leukoplakia were assessed by OCT4 immunohistochemically. Oral squamous cell carcinoma was used as a control. RESULT: no expression of OCT 4 was observed in any cases of oral leukoplakia. CONCLUSION: The molecular mechanisms of Oct4 regulation and in particular of its switch on and off in tissues depends upon its microenvironment, which makes it challenging in fundamental and applied research fields of regenerative medicine and cancer therapy. It's better that patients should undergo multiple biopsies for the early detection of malignant transformation with close follow-up during the first two to three years, a large amount of work remains to be done with multi-marker panel investigation, as cure rates have remained constant over three decades.

Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models.

BACKGROUND: Given that aberrant activation of epidermal growth factor receptor family receptors (ErbB) is a common event in oral squamous cell carcinoma, and that high expression of these receptor proteins is often associated with poor prognosis, this rationalizes the approach of targeting ErbB signaling pathways to improve the survival of patients with oral squamous cell carcinoma. However, monotherapy with the ErbB blocker afatinib has shown limited survival benefits. OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma. METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models. RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models. CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.

In vitro evaluation of dual-antigenic PV1 peptide vaccine in head and neck cancer patients.

Peptide vaccines derived from tumour-associated antigens have been used as an immunotherapeutic approach to induce specific cytotoxic immune response against tumour. We previously identified that MAGED4B and FJX1 proteins are overexpressed in HNSCC patients; and further demonstrated that two HLA-A2-restricted 9-11 amino acid peptides derived from these proteins were able to induce anti-tumour immune responses in vitro independently using PBMCs isolated from these patients. In this study, we evaluated the immunogenicity and efficacy of a dual-antigenic peptide vaccine (PV1), comprised of MAGED4B and FJX1 peptides in HNSCC patients. We first demonstrated that 94.8% of HNSCC patients expressed MAGED4B and/or FJX1 by immunohistochemistry, suggesting that PV1 could benefit the majority of HNSCC patients. The presence of pre-existing MAGED4B and FJX1-specific T-cells was detected using a HLA-A2 dimer assay and efficacy of PV1 to induce T-cell to secrete cytotoxic cytokine was evaluated using ELISPOT assay. Pre-existing PV1-specific T-cells were detected in all patients. Notably, we demonstrated that patients' T-cells were able to secrete cytotoxic cytokines upon exposure to target cells expressing the respective antigen post PV1 stimulation. Furthermore, patients with high expression of MAGED4B and FJX1 in their tumours were more responsive to PV1 stimulation, demonstrating the specificity of the PV1 peptide vaccine. Additionally, we also demonstrated the expression of MAGED4B and FJX1 in breast, lung, colon, prostate and rectal cancer suggesting the potential use of PV1 in these cancers. In summary, PV1 could be a good vaccine candidate for the treatment of HNSCC patients and other cancers expressing these antigens.

Multi-ethnic variations in the practice of oral cancer risk habits in a developing country.

OBJECTIVE: To elucidate ethnic variations in the practice of oral cancer risk habits in a selected Malaysian population. METHODS: This retrospective case-control study involves 790 cases of cancers of the oral cavity and 450 controls presenting with non-malignant oral diseases, recruited from seven hospital-based centres nationwide. Data on risk habits (smoking, drinking, chewing) were obtained using a structured questionnaire via face-to-face interviews. Multiple logistic regression was used to determine association between risk habits and oral cancer risk; chi-square test was used to assess association between risk habits and ethnicity. Population attributable risks were calculated for all habits. RESULTS: Except for alcohol consumption, increased risk was observed for all habits; the highest risk was for smoking + chewing + drinking (aOR 22.37 95% CI 5.06, 98.95). Significant ethnic differences were observed in the practice of habits. The most common habit among Malays was smoking (24.2%); smoking + drinking were most common among Chinese (16.8%), whereas chewing was the most prevalent among Indians (45.2%) and Indigenous people (24.8%). Cessation of chewing, smoking and drinking is estimated to reduce cancer incidence by 22.6%, 8.5% and 6.9%, respectively. CONCLUSION: Ethnic variations in the practice of oral cancer risk habits are evident. Betel quid chewing is the biggest attributable factor for this population.

Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance.

BACKGROUND: Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy. OBJECTIVES: The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes. MATERIALS AND METHODS: Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software. RESULTS: Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC. CONCLUSION: Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways.

Prognostic significance of VEGF-C in predicting micrometastasis and isolated tumour cells in N0 oral squamous cell carcinoma.

BACKGROUND: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a well-known independent prognostic factor. However, the identification of occult tumour cells within the lymph nodes has remained a challenge for the pathologist as well as the clinician. OBJECTIVE: The aim of this study was to determine the prevalence of micrometastasis and isolated tumour cells (ITCs) in pathologically staged N0 OSCC of the tongue and buccal mucosa and to assess its correlation with vascular endothelial growth factor C, (VEGF-C) expression in the primary tumour. METHODS: Thirty-four cases of N0 OSCC comprising of 17 cases each from the tongue and buccal mucosa were evaluated by immunohistochemistry for VEGF-C expression. The corresponding lymph nodes from levels I and II were pathologically examined and cross-detected for micrometastasis and ITCs with desmoglein 3 (DSG3). RESULTS: The prevalence of micrometastasis and ITCs in OSCC of the tongue and buccal mucosa was 23.5% and 17.6%, respectively. A total of 12 out of 151 lymph nodes contained micrometastatic tumour foci and ITCs. A higher expression of VEGF-C in the primary tumour was associated with a greater probability for the occurrence of micrometastasis and ITCs in the lymph nodes. CONCLUSION: High expression of VEGF-C in the primary tumour may be a good determinant for detection of occult tumour cells in the lymph nodes of OSCC cases.

Caveolin 1 (Cav-1) and actin-related protein 2/3 complex, subunit 1B (ARPC1B) expressions as prognostic indicators for oral squamous cell carcinoma (OSCC).

Caveolin-1 (Cav-1) and Actin-Related Protein 2/3 Complex, Subunit 1B (ARPC1B) have been implicated in various human cancers, yet its role in tumorigenesis remains controversial. Therefore, this study aims to determine the protein expression of these two genes in oral squamous cell carcinomas (OSCCs) and to evaluate the clinical and prognostic impact of these genes in OSCC. Protein expressions of these two genes were determined by immunohistochemistry technique. The association between Cav-1 and ARPC1B with clinico-pathological parameters was evaluated by Chi-square test (or Fisher exact test where appropriate). Correlation between the protein expressions of these 2 genes with survival was analyzed using Kaplan-Meier and Cox regression models. Cav-1 and ARPC1B were found to be significantly over-expressed in OSCC compared to normal oral mucosa (p = 0.002 and p = 0.033, respectively). Low level of ARPC1B protein expression showed a significant correlation with lymph node metastasis (LNM) (p = 0.010) and advanced tumor staging (p = 0.003). Kaplan-Meier survival analyses demonstrated that patients with over-expression of Cav-1 protein were associated with poor prognosis (p = 0.030). Adjusted multivariate Cox regression model revealed that over-expression of Cav-1 remained as an independent significant prognostic factor for OSCC (HRR = 2.700, 95 % CI 1.013-7.198, p = 0.047). This study demonstrated that low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients.

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications.

BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC.