Characterisation and prognostic value of tertiary lymphoid structures in oral squamous cell carcinoma

BACKGROUND: Oral squamous cell carcinomas are often heavily infiltrated by immune cells. The organization of B-cells, follicular dendritic cells, T-cells and high-endothelial venules into structures termed tertiary lymphoid structures have been detected in various types of cancer, where their presence is found to predict favourable outcome. The purpose of the present study was to evaluate the incidence of tertiary lymphoid structures in oral squamous cell carcinomas, and if present, analyse whether they were associated with clinical outcome. METHODS: Tumour samples from 80 patients with oral squamous cell carcinoma were immunohistochemically stained for B-cells, follicular dendritic cells, T-cells, germinal centre B-cells and high-endothelial venules. Some samples were sectioned at multiple levels to assess whether the presence of tertiary lymphoid structures varied within the tumour. RESULTS: Tumour-associated tertiary lymphoid structures were detected in 21 % of the tumours and were associated with lower disease-specific death. The presence of tertiary lymphoid structures varied within different levels of a tissue block. CONCLUSIONS: Tertiary lymphoid structure formation was found to be a positive prognostic factor for patients with oral squamous cell carcinoma. Increased knowledge about tertiary lymphoid structure formation in oral squamous cell carcinoma might help to develop and guide immune-modulatory cancer treatments

Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma

Accepted manuscript version. The final publication is available at Springer via http://dx.doi.org/10.1007/s13277-015-4036-4Background: Staging of oral squamous cell carcinoma is based on the TNM system, which has been deemed insufficient for prognostic purposes. Hence, better prognostic tools are needed to reflect the biological diversity of these cancers. Previously, high numbers of specialized blood vessels called high-endothelial venules have been reported to be associated with prolonged survival in patients with breast cancer. In this study, we analysed the prognostic value and morphological characteristics of tumour-associated high-endothelial venules in oral cancer. Methods: The presence of tumour-associated high-endothelial venules was evaluated by immunohistochemistry in 75 patients with oral squamous cell carcinoma and analysed with correlation to clinicopathological parameters, patients’ survival, and vessel morphology. Ten of the samples were analysed at multiple levels to evaluate intratumoural heterogeneity. Results: The presence of tumour-associated high-endothelial venules was found to be associated with lower disease-specific death in multivariate regression analyses (P=0.002). High-endothelial venules were present in all (n=53) T1-T2 tumours, but only in two-thirds (n=14) of the T3-T4 tumours. The morphology of high-endothelial venules was heterogeneous and correlated with lymphocyte density. High-endothelial venules were found to be distributed homogeneously within the tumours. Conclusion: We found the presence of tumour-associated high-endothelial venules to be an easy-to-use, robust, and independent positive prognostic factor for patients with oral cancer. Absence of these vessels in advancedstage tumours might identify patients with more aggressive disease. Evaluating the presence of tumour-associated high-endothelial venules might help to tailor the treatment of oral cancer patients to their individual need

Laryngo-tracheal resections in the Nordic countries : an option for further centralization?

Purpose We aimed to obtain information on the number of Nordic centers performing tracheal resections, crico-tracheal resections, and laryngo-tracheal reconstructions, as well as the patient volume and the standard regimens associated with these procedures. Methods Consultants at all Departments of Otorhinolaryngology-Head and Neck Surgery (ORL-HNS, n = 22) and Thoracic Surgery (n = 21) in the five Nordic countries were invited (April 2018-January 2019) to participate in an online survey. Results All 43 departments responded to the survey. Twenty departments declared to perform one or more of the three types of tracheal resections. At five hospitals, departments of ORL-HNS and Thoracic Surgery perform these operations in collaboration. Hence, one or more of the tracheal operations in question are carried out at 15 centers. The median annual number of tracheal operations per center is five (range 1-20). Great variations were found regarding contraindications (relative and absolute) for surgery, the use of guardian sterno-mental sutures (all patients, 33%; selected cases, 40% of centers), prophylactic antibiotic therapy (cefuroxime +/- metronidazole, penicillin +/- metronidazole, clindamycin, imipenem, or none), post-operative follow-up time (range: children: 3-120 months; adults: 0-60 months), and the performance of postoperative bronchoscopy. Conclusions Fifteen centers each perform a low number of annual operations with significant variations in the selection of patients and the clinical setup, which raises the question if a higher degree of collaboration and centralization would be warranted. We encourage Nordic transnational collaboration, pursuing alignment on central management issues, and establishment of a common prospective database for future tracheal resection surgery.Peer reviewe

Stromal impact on tumor growth and lymphangiogenesis in human carcinoma xenografts

Squamous cell carcinomas (SCCs) arising in the oral cavity are associated with poor survival, mainly due to metastatic disease. In contrast, skin SCCs rarely metastasize and are usually curable. To study influence of tongue and skin stroma on cancer growth and induction of lymphangiogenesis, xenograft tumors of human carcinoma cells were established either in tongue or skin of BALB/c nude mice. Two oral and two skin SCC cell lines were used, as well as an endometrial adenocarcinoma cell line. Tongue tumors established from all cell lines were larger than corresponding skin tumors. Peritumoral lymphatic vessel density was up to five times higher in tongue than in corresponding skin tumors, and mRNA level of the lymphangiogenic growth factor vascular endothelial growth factor (VEGF)-C was twice as high in tongue tumors compared with corresponding skin tumors. Contrary to lymphatic vessel density, blood vessel density was higher in skin tumors than in tongue tumors. In a cohort of patient samples, lymphatic vessel density was found to be higher in tongue SCCs compared with skin SCCs, supporting a clinical relevance of our findings. Our results show that the tumor stroma has a profound impact on cancer growth and induction of lymphangiogenesis and angiogenesis. The difference in lymphatic vessel density between tongue and skin tumors may be important in directing metastatic potential of tumors arising in these organs

Transoral Robotic Surgery in the Nordic Countries : Current Status and Perspectives

Background: The five Nordic countries with a population of 27 M people form a rather homogenous region in terms of health care. The management of head and neck cancer is centralized to the 21 university hospitals in these countries. Our aim was to gain an overview of the volume and role of transoral robotic surgery (TORS) and to evaluate the need to centralize it in this area as the field is rapidly developing. Materials and Methods: A structured questionnaire was sent to all 10 Departments of Otorhinolaryngology-Head and Neck Surgery in the Nordic countries having an active programme for TORS in December 2017. Results: The total cumulative number of performed robotic surgeries at these 10 Nordic centers was 528 and varied between 5 and 240 per center. The median annual number of robotic surgeries was 38 (range, 5-60). The observed number of annually operated cases remained fairly low ( Conclusions: The present results showing a limited volume of performed surgeries call for considerations to further centralize TORS in the Nordic countries.Peer reviewe

Plectin as a prognostic marker in non-metastatic oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate. In general, patients diagnosed with small tumors have a fairly good prognosis, but some small tumors have an aggressive behavior leading to early death. There are at present no reliable prognostic biomarkers for oral cancers. Thus, to optimize treatment for the individual patient, there is a need for biomarkers that can predict tumor behavior. Method: In the present study the potential prognostic value of plectin was evaluated by a tissue microarray (TMA) based immunohistochemical analysis of primary tumor tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC. The expression of plectin was compared with clinicopathological variables and 5 year survival. Results: The statistical analysis revealed that low expression of plectin in the tumor cells predicted a favorable outcome for patients with non-metastatic disease (p = 0.008). Furthermore, the expression of plectin was found to correlate (p = 0.01) with the expression of uPAR, which we have previously found to be a potential prognostic marker for T1N0 tumors. Conclusions: Our results indicate that low expression of plectin predicts a favorable outcome for patients with non-metastatic OSCC and the expression level of plectin may therefore be used in the treatment stratification for patients with early stage disease

Prognostic markers in oral squamous cell carcinoma

Avhandlingen er basert på 5 artikler. Vi har retrospektivt innhentet klinisk informasjon om 133 pasienter diagnostisert med cancer i munnhulen ved UNN i perioden 1986-2001, og laget Tissue Micro Arrays (TMA) av tumorvev fra de respektive pasientenes svulster. Den første artikkelen er en epidemiologisk beskrivelse av materialet. Artikkel 2 og 3 omfatter ulike potensielle prognostiske markører for oral cancer, basert på immunhistokjemiske undersøkelser på TMA blokkene. I artikkel 2 er uPAR, PAI-1 de mest interessante, hvor vi finner en statistisk signifikant sammenheng mellom vevsuttrykk og sykdomsspesifikk overlevelse i pasienter med T1-svulster. I artikkel 3 er hovedfokuset på plectin. Uttrykket av plectin i vevet er statistisk signifikant knyttet til overlevelse for alle pasienter uten spredning av sykdommen til regional lymfeknuter(N0)ved diagnose. Vi fant også en sterk korrelasjon mellom uttrykket av uPAR og plectin i tumorvevet. I artikkel 4 har vi gjort undersøkelser på fullsnitt på 80 av svulstene for å kartlegge forekomsten av tertiære lymfoide organer (TLOs) i oral cancer, noe som ikke har vært gjort tidligere. Forekomsten av disse var også signifikant knyttet til prognose. Videre beskriver den siste artikkelen en indirekte, mer praktisk metode for å påvise disse immunologiske strukturene i vevet, ved å identifisere high endothelial venules (HEVs) i omgivelsene rundt TLOs. Pasienter med HEVs hadde signifikant mindre risiko for å dø av sykdommen enn de uten. Vår konklusjon er at vi har gjort flere interessante funn som fortjener å bli validert i en større studie

Clinicopathological characteristics of oral squamous cell carcinoma in Northern Norway: a retrospective study

BACKGROUND: The main aim of the study was to evaluate if patients with oral squamous carcinomas in Northern Norway differ from patients in other countries with regard to clinicopathological characteristics and also study the influence of risk factors. Such a comparison is of demographical interest, and also important for the interpretation of result from studies on prognostic biomarkers. METHODS: We describe clinicopathological characteristics of 133 North Norwegian patients diagnosed with squamous cell carcinoma of the oral cavity in the period 1986–2002, and evaluate the significance of different risk factors. RESULTS: The cohort consisted of 69 men and 64 women, giving male/female ratio of 1.1. Forty-seven of the 133 patients (35%) died of the disease within 5 years from diagnosis. There was no significant difference between the genders concerning time to disease specific death, even though men both smoked and drank more alcohol than women. As expected, the strongest predictors for disease specific death were tumour size and the presence of regional lymph node metastasis. We also found that heavy smokers and drinkers presented with more advanced disease, more often localized to the floor of mouth compared to non-smoking and abstinent patients, who more often presented with tumours of the mobile tongue. CONCLUSIONS: Our results correlate well with previously published clinicopathological data on comparable cohorts, which is important when considering the applicability of results from biomarker studies performed on this material compared to other cohorts, and vice versa

Plectin as a prognostic marker in non-metastatic oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate. In general, patients diagnosed with small tumors have a fairly good prognosis, but some small tumors have an aggressive behavior leading to early death. There are at present no reliable prognostic biomarkers for oral cancers. Thus, to optimize treatment for the individual patient, there is a need for biomarkers that can predict tumor behavior. Method: In the present study the potential prognostic value of plectin was evaluated by a tissue microarray (TMA) based immunohistochemical analysis of primary tumor tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC. The expression of plectin was compared with clinicopathological variables and 5 year survival. Results: The statistical analysis revealed that low expression of plectin in the tumor cells predicted a favorable outcome for patients with non-metastatic disease (p = 0.008). Furthermore, the expression of plectin was found to correlate (p = 0.01) with the expression of uPAR, which we have previously found to be a potential prognostic marker for T1N0 tumors. Conclusions: Our results indicate that low expression of plectin predicts a favorable outcome for patients with non-metastatic OSCC and the expression level of plectin may therefore be used in the treatment stratification for patients with early stage disease