Oral Oncology - Articles in Press

Comments on “Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples” by Saleh et al., Oral Oncol 46 (2010) 379–386 - Corrected Proof

Matilda Rentoft, Göran Laurell, Philip J. Coates, Björn Sjöström, Karin Nylander — 2010-07-26

We recently read the interesting article “Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples” in Oral Oncology, by Saleh et al. and would like to compare these data to a study that we ourselves recently published. The design of the two studies is very similar and both evaluated the use of archival samples for measuring gene expression changes in oral squamous cell carcinoma (OSCC) using microarray. The study by Saleh was performed on SCC from the buccal mucosa whereas we analysed SCC of the tongue.

Classic Kaposi’s sarcoma in Han Chinese and useful tools for differential diagnosis - Corrected Proof

Xin Wang, Xing Wang, Deguang Liang, Ke Lan, Wei Guo, Guoxin Ren — 2010-07-26

Summary: Kaposi’s sarcoma (KS) is a common AIDS-related malignant neoplasm in the head and neck region, especially in the oral cavity, but is rarely described in the HIV-negative and non-immunosuppressed individual. Our case is of interest, because it is the first case in which manifestation of the KS occurred in the face and head areas in a patient with a Han ethnic background who had an adequate immune system. The lesions were diagnosed as angiosarcomas twice. The clinical presentation, therapeutic options, and tools for differentiating Kaposi sarcoma from other vascular and nonvascular spindle cell lesions are presented, and the relevant literature is reviewed.

Association between the polymorphisms in exon 12 of hypoxia-inducible factor-1α and the clinicopathological features of oral squamous cell carcinoma - Corrected Proof

2010-07-26

Summary: Oral squamous cell carcinoma (OSCC) is a common malignancy. The incidence of OSCC is particularly high in some Asian countries because of the popularity of the habit of chewing areca. Hypoxia-inducible factor-1α (HIF-1α) is up-regulated in the hypoxic microenvironment to enhance tumor survival. Five polymorphisms have been identified in exon 12 of HIF-1α including the C1772T polymorphism causing P582S, and the G1790A polymorphism causing A588T of the HIF-1α protein. This study investigated the relationship between these functional polymorphisms and the risk of progression of OSCC. PCR and direct sequencing were utilized to compare the genotypic polymorphism and allelic frequency of HIF-1α in 96 normal controls and 305 OSCC patients. No statistically significant difference in C1772T and G1790A genotypes and allelic frequency between control and OSCC patients was found. However, multivariate analysis indicated that the A carrier of HIF-1α G1790A in OSCC patients was significantly higher in larger tumors than in the contrasting group with an adjusted odds ratio of 2.92. The T carrier of HIF-1α C1772T in buccal cancer patients was significantly higher in the non-areca-chewing group with an adjusted odds ratio of 0.111. The buccal cancer patients with C1772T or G1790A had lower recurrence frequency with an odds ratio of 0.266. These findings may suggest a correlation between the HIF-1α C1772T and G1790A polymorphisms and the growth of OSCC, and the decrease of OSCC recurrence frequency.

Angiogenin-mediated ribosomal RNA transcription as a molecular target for treatment of head and neck squamous cell carcinoma - Corrected Proof

Lili Chen, Guo-fu Hu — 2010-07-26

Summary: Squamous cell carcinoma of the head and neck (HNSCC) is the eighth most common disease, affecting approximately 640,000 patients worldwide each year. Despite recent advances in surgery, radiotherapy, and chemotherapy, the overall cure for patients with HNSCC has remained at less than 50% for many decades. Patients with recurrent and metastatic disease have a median survival of only 6–10months. Systemic chemotherapy is the only treatment option for those patients. New treatment options are thus desperately needed to supplement, complement, or replace currently available therapies. New agents that target molecular and cellular pathways of the disease pathogenesis of HNSCC are promising candidates. One class of these new agents is angiogenesis inhibitors that have been proven effective in the treatment of advanced colorectal, breast, and non-small cell lung cancers. Similar to other solid tumors, angiogenesis plays an important role in the pathogenesis of HNSCC. A number of angiogenic factors including vascular endothelial growth factor (VEGF) and angiogenin (ANG) have been shown to be significantly upregulated in HNSCC. Among them, ANG is unique in which it is a ribonuclease that regulates ribosomal RNA (rRNA) transcription. ANG-stimulated rRNA transcription has been shown to be a general requirement for angiogenesis induced by other angiogenic factors. ANG inhibitors have been demonstrated to inhibit angiogenesis and tumor growth induced not only by ANG but also by other angiogenic factors. As the role of ANG in HNSCC is being unveiled, the therapeutic potential of ANG inhibitors in HNSCC is expected.

Overexpression of p63 is associated with radiation resistance and prognosis in oral squamous cell carcinoma - Corrected Proof

Maximilian Moergel, Eva Abt, Marcus Stockinger, Martin Kunkel — 2010-07-26

Summary: Background: The tumor suppressor homologue p63 is expressed in basal and parabasal layers of intraoral mucosa. Full length transcripts with transactivational domain (TA forms) present with homology to p53 and implicate functions governing cell proliferation, differentiation and apoptosis control. To date studies show an increase of p63 expression in oral dysplasia and additionally high expression levels correlated with poor prognosis for patients with OSCC, whereas a possible link to radiation resistance of tumors has not been investigated yet. In the present study we tested the hypothesis for p63 being a marker of radioresistance and overall survival in OSCC. Methods: p63 Expression was labeled by immunohistochemistry in pre-treatment biopsies collected from 33 patients with OSCC. Quantification of the labeling index (Li) based on the relation of p63 positive cells to overall tumor cell count. Histological examination of the resection specimen allowed categorization of the radiation response. Statistical analyses of the association between Li and radiation response were performed. Survival analysis utilized Kaplan–Meier estimates and additionally a Cox regression model was built for p63 (Li), T stage, N-stage and chemotherapy and presented as hazard ratios. Results: All tumors had enhanced p63 expression. The median Li was 63.1% (range 36–87%). Tumors with a p63 positive cell count>63.1% showed increased resistance to radiation (p=0.027). Overall survival was higher (p=0.001) for patients with low Li ( median value) and multivariate Cox regression analysis confirmed the significance of p63 as a prognostic marker of survival. Conclusions: The results of this analysis advocate p63 expression in pre-treatment tumor tissue to be a marker of radiation resistance in OSCC, with high expression levels being associated with poor radiation response and shorter survival. The promising results of this biomarker should now be confirmed by a study with larger patient counts.

Hypopharyngeal carcinoma after radiation for tuberculosis: Radiation-induced carcinoma - Corrected Proof

2010-07-26

Summary: Radiation may cause radiation-induced cancers after a long latency period. In a group of 111 patients surgically treated for hypopharyngeal carcinoma, patients previously treated with radiotherapy for tuberculosis in the neck were compared to patients without previous radiotherapy. Seven patients (7.4%) underwent radiotherapy (median age 15years) and developed a hypopharyngeal carcinoma (median age 70years, median latency period 54.4year). Considering this long latency period and the localisation in the previous radiation field these tumours can be classified as potentially radiation-induced carcinomas. Patients with potentially radiation-induced carcinomas were significantly older when the hypopharyngeal carcinoma was diagnosed (p=0.048), were more frequently females (p=0.05) and had a worse 5-year regional control rate (p=0.048). When radiotherapy is considered in young patients the risk of induction of tumours has to be kept in mind.

Endothelins and their receptors as biological markers for oral cancer - Corrected Proof

Renata R. Hoffmann, Liliane S. Yurgel, Maria M. Campos — 2010-07-26

Summary: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies recognized nowadays, and represents a public health problem. Its early detection is the better alternative to provide a good quality of life for the patients. During the last years, several studies have identified potential biomarkers of OSCC progression and prognosis. Endothelins and their receptors are involved in several pathophysiological conditions and in various cancer types. The present review article discusses whether the endothelin system would represent a biomarker for OSCC.

Midkine expression in malignant salivary gland tumors and its role in tumor angiogenesis - Corrected Proof

2010-07-16

Summary: The aims of this study were to investigate midkine (MK) expression patterns in salivary gland tumors (SGTs) and to evaluate the correlation between MK expression and the degree of malignancy. We performed immunohistochemistry to examine MK expression in specimens of adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and pleomorphic adenoma (PA). In addition, we performed immunohistochemistry for CD31 and measured microvessel density (MVD), which is an indicator of angiogenesis. Immunohistochemistry showed that MK protein expression was significantly higher in specimens of malignant SGTs (ACC [P<0.01] and MEC [P<0.001]) than in benign SGT (PA) samples. Furthermore, MVD values tended to be higher in cases that exhibited high expression of MK, which indicated a significant correlation between the degree of MK expression and MVD (P<0.001). These results suggest that MK may play important roles in malignant transformation and tumor angiogenesis in SGTs.

Prognostic evaluation of oral tongue cancer: Means, markers and perspectives (I) - Corrected Proof

Ibrahim O. Bello, Ylermi Soini, Tuula Salo — 2010-07-16

Summary: Oral (mobile) tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity. Due to the inherent disadvantages of the mobile tongue OTSCC behaves aggressively and is generally associated with higher rates of occult metastasis and neck nodal metastasis than any other cancer of the oral cavity. The prognosis remains relatively poor and is still heavily reliant on TNM (tumor, node, metastasis) staging of the tumor despite a vast array of literature on possible prognostic indicators. This is a two-part article which examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this first part, we discuss the relative merits of the methods used in prognostic studies and the clinicopathologic prognostic factors.

Cytology and histology have limited added value in prognostic models for salivary gland carcinomas - Corrected Proof

2010-07-16

Summary: Univariate analyses on malignant salivary gland tumors report a strong relation of histological subtypes and prognosis. However, multivariate analyses with sufficient patients and reflecting the broad spectrum of putative prognostic factors are rare.In order to study the prognostic value of cytology and histology in salivary carcinoma we performed multivariate analyses on 666 newly diagnosed patients.In multivariate analyses sex, tumor size, N- and M-staging, localization, comorbidity, skin involvement and pain were independent predictors of survival. Histology was an independent prognostic factor, mainly because acinic cell carcinoma acted differently from the other histological subtypes. However, a simple prognostic model without cytology and/or histology has similar predictive power compared to more elaborate models.The added prognostic value of cytology and/or histology factors in salivary carcinoma is limited, largely due to the combined prognostic value of other prognostic factors such as tumor size, N- and M-classification and comorbidity.

Prognostic evaluation of oral tongue cancer: Means, markers and perspectives (II) - Corrected Proof

Ibrahim O. Bello, Ylermi Soini, Tuula Salo — 2010-07-16

Summary: Squamous cell carcinoma of the oral (mobile) tongue (OTSCC) is increasingly regarded as a biologically different entity compared to cancer affecting other oral sites. It is more aggressive and generally associated with a higher rate of metastasis. This is the concluding part of our two-part article that examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this part, we continue our discussion of the histopathologic and molecular prognostic factors, and serum and salivary biomarkers in of OTSCC, and emphasize the need to regard OTSCC as a high risk variant of oral cancer. We conclude with future direction of prognostic studies of OTSCC.