Timo Atula

Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue

Background:The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial–mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types.Methods:Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above.Results:A significant correlation between Bmi-1 protein expression and recurrence (log-rank test, P=0.005) was detected. Snail and c-myc expression did not correlate with prognosis. Snail expression correlated with histopathological grade (Fishers exact test, P=0.007) and with the invasion depth of tumours (χ2-test, P=0.037).Conclusion:Negative Bmi-1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients.

Assessment of cervical lymph node status in head and neck cancer patients: palpation, computed tomography and low field magnetic resonance imaging compared with ultrasound-guided fine-needle aspiration cytology

OBJECTIVE Since the assessment of lymph node metastases in head and neck cancer patients remains a major problem, the findings of different imaging methods and the role of these methods in the clinical management are compared. MATERIAL AND METHODS Palpation, computed tomography (CT) and low field magnetic resonance imaging (MRI; 0.1 T) are evaluated and compared with ultrasound-guided fine-needle aspiration cytology (US-guided FNAC) prospectively in 105 consecutive patients with a primary cancer in the head and neck region. RESULTS In the subgroup of 86 patients with palpable normal necks, CT showed lymph nodes fulfilling the radiologic criteria for malignancy in 27% (23/86), MRI in 17% (10/60) and US in 14% (12/86) of the patients US guided FNAC usually showed malignancy in necks containing lymph nodes with central necrosis on CT, but the enlarged lymph nodes that were also common on the contralateral side were often benign on cytology. In 5 patients, FNAC under US-guidance showed malignancy although none of them had lymph nodes fulfilling the radiologic criteria for malignancy. In the other subgroup of 19 patients with palpable metastatic necks, 2 patients had bilateral metastases detected by all imaging methods but not by palpation. CONCLUSION CT is superior to low field MRI in depicting small pathologic lymph nodes. Unlike lymph node structure, lymph node size is not a highly reliable criterion for malignancy. The findings must be correlated in relation to the primary disease. Since FNAC under US-guidance offers additional information about enlarged lymph nodes and since it can show malignancy in small lymph nodes not found by other methods, it can be recommended for most head and neck cancer patients irrespective of the use of CT or MRI.

High CIP2A immunoreactivity is an independent prognostic indicator in early-stage tongue cancer

Background:No reliable prognostic markers exist for squamous cell carcinoma of the tongue, and its prognosis can even in early stages be unpredictable and survival poor despite treatment. A potential marker is oncoprotein cancerous inhibitor of PP2A (CIP2A), which acts as a prognostic marker in gastric and non-small cell lung cancers.Methods:We collected specimens of 73 stage T1N0M0 and T2N0M0 oral squamous cell carcinomas of the tongue, as well as samples from normal oral mucosa, dysplastic lesions, and invasive carcinomas (n=39). All samples were stained for CIP2A by immunohistochemistry. Survival curves were constructed according to the Kaplan–Meier method. The Cox proportional hazard model served for univariate and multivariate survival analysis.Results:High CIP2A immunoreactivity predicted poor survival in tongue cancer patients (P=0.027, logrank test). In multivariate survival analysis, CIP2A was an independent prognostic factor (HR 2.02, 95% confidence interval 1.07–3.82, P=0.030). Cytoplasmic CIP2A expression was higher in severe dysplasia than in mild dysplasia.Conclusion:Our results suggest that high CIP2A expression characterises aggressive disease. Acting as a prognostic marker it might be of help when choosing patients for adjuvant treatment in tongue cancer patients.

Complications of Acute Sinusitis in Children

Acute sinusitis is often a mild, self-limiting disease. However, in some cases, especially among children, sinusitis may become a severe, even life-threatening, disease. To examine the nature of complications of acute sinusitis, we studied the cases of children treated at the Helsinki University ENT Hospital, because of a complication caused by acute sinusitis from January 1997 to September 1998. There were 12 children (4 girls, 8 boys), whose ages ranged from 16 months to 16 years. One child had an epidural abscess, one got meningitis and cavernous sinus thrombosis, five had orbital cellulitis, one of whom lost her vision permanently in one eye, and five had preseptal cellulitis. All the children were treated with intravenous antibiotics and all, except the youngest, were treated with a direct sinus puncture. An operation (intranasal antrostomy, orbital drainage, functional endoscopic sinus surgery or adenoidectomy) was performed on six patients. In the majority of children, acute sinusitis is a mild self-limiting disease. However, severe complications still exist. When a complication of sinusitis is suspected, it is of utmost importance that the child be sent immediately to a hospital for proper diagnosis and treatment.Acute sinusitis is often a mild, self-limiting disease. However, in some cases, especially among children, sinusitis may become a severe, even life-threatening, disease. To examine the nature of complications of acute sinusitis, we studied the cases of children treated at the Helsinki University ENT Hospital, because of a complication caused by acute sinusitis from January 1997 to September 1998. There were 12 children (4 girls, 8 boys), whose ages ranged from 16 months to 16 years. One child had an epidural abscess, one got meningitis and cavernous sinus thrombosis, five had orbital cellulitis, one of whom lost her vision permanently in one eye, and five had preseptal cellulitis. All the children were treated with intravenous antibiotics and all, except the youngest, were treated with a direct sinus puncture. An operation (intranasal antrostomy, orbital drainage, functional endoscopic sinus surgery or adenoidectomy) was performed on six patients. In the majority of children, acute sinusitis is a mild self-limiting disease. However, severe complications still exist. When a complication of sinusitis is suspected, it is of utmost importance that the child be sent immediately to a hospital for proper diagnosis and treatment.

Human papillomavirus, Epstein–Barr virus, human herpesvirus 8 and human cytomegalovirus involvement in salivary gland tumours

Human papillomaviruses (HPV) are involved in the etiology of both benign and malignant epithelial lesions. The occurrence of HPV types 16 and 18 in gynecological squamous cell carcinomas is also well known. Of the herpesviruses, Epstein-Barr virus (EBV) is associated with, for example, undifferentiated nasopharyngeal carcinoma, endemic Burkitts lymphoma and immunoblastic lymphoma, and human herpesvirus 8 (HHV-8) with Kaposis sarcoma. As little is known about the etiological factors of salivary gland tumours, the presence of HPV, EBV, HHV-8 and human cytomegalovirus (CMV) in these tumours were examined. Fresh tissue samples obtained from 19 consecutive pleomorphic adenomas and 19 malignant salivary gland tumours were analyzed with polymerase chain reaction. Two samples showed EBV DNA positivity, a lymphoma of the parotid gland and a pleomorphic adenoma arising in the nasal cavity. HPV, HHV-8 and CMV DNA were not detected in any of the tumour samples. The results indicate that HPV, HHV-8 and CMV do not seem to have any role in the etiology of salivary gland neoplasms.

Basal cell adenocarcinoma of the parotid gland: a case report and review of the literature.

Basal cell adenocarcinoma is a rare salivary gland tumour. A DNA diploid parotid gland basal cell adenocarcinoma, with a low mitotic rate, in a 78-year-old female patient is described. Total removal of the affected salivary gland without sacrificing the facial nerve gave a good therapeutic result.

Fine-needle aspiration cytology of submandibular gland lesions.

The usefulness of fine-needle aspiration cytology (FNAC) in the diagnosis and treatment of submandibular gland lesions is not well known. The 210 FNACs taken from submandibular gland lesions at Turku University Central Hospital between 1984 and 1991 were reviewed. Of these FNACs, 78 samples from primary lesions were confirmed histologically. Within this subset 10 FNACs were taken from benign neoplasms, all of which were correctly classified (sensitivity 100 per cent; specificity 88 per cent). Only four of the 14 FNACs from malignant lesions were cytologically considered malignant (sensitivity 29 per cent). On the other hand, four FNACs raised a false suspicion of malignancy (specificity 6 per cent). Out of 54 FNACs from non-neoplastic lesions 43 were correct (sensitivity 80 per cent; specificity 63 per cent). There were 104 patients (123 FNACs), who had not been operated on: the follow-up of these patients shows that in this subset of FNACs there were no false malignant but probably one false benign finding (1 per cent). We conclude that FNAC can offer valuable information about the type of the submandibular gland lesion, but the decision of operative and other treatment should not be based solely on the result of FNAC.

How many sentinel nodes should be harvested in oral squamous cell carcinoma

The number of harvested lymph nodes when performing sentinel lymph node (SLN) biopsy remains controversial. The aim of this study was to examine the maximum number of nodes to be harvested for histopathological analysis. We also wanted to determine if the level of radioactivity within a SLN or its size were indicators for the likelihood of nodal metastases. The SLNs from 34 neck dissection specimens from patients with T1/T2 N0 oral and oropharyngeal carcinomas were included. Altogether 76 SLNs were measured for radioactivity and lymph node dimensions and volume. Tumour was identified in 16 of 76 nodes (positive nodes), and the remaining 60 nodes were free from tumour (negative nodes). In 9 of 16 cases, metastases were in the hottest node. Two patients had more than one positive SLN: the first and fourth hottest in one and the second and fourth hottest nodes in another contained tumour. However, all patients would have been staged accurately if only the hottest three sentinel nodes had been retrieved. Lymph nodes that contained tumour had a greater maximum diameter than non-metastatic SLNs. To stage the neck accurately, only the three hottest lymph nodes required sampling.

Expression of toll-like receptors in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma—an in vivo and in vitro study

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past decades in many western countries. This trend is mainly attributed to the human papillomavirus (HPV). Cancer-related actions of immunological defense systems are being intensively researched. Human toll-like receptors (TLRs) are a family of pattern recognition receptors that participate in the immunological defense against pathogens, but their actions are also linked to cancer. The expression of TLRs in cervical epithelium alters both during the clearance of HPV infection and the HPV-induced neoplasia, but the expression of TLRs has not been studied in OPSCC. Thirty-five paraffin-embedded, formalin-fixed, squamous cell carcinoma tissue specimens were analyzed for TLRs 2, 3, 4, 5, 7, and 9 and HPV and p16 statuses. The TLR 9 expression was lower in HPV-positive tumors compared with HPV-negative tumors. TLR 7 was expressed in all cancer specimens, but elevated expression was evident in HPV and/or p16-positive tumors. The majority of p16-positive tumors did not express TLR 5, whereas its expression was stronger in p16-negative tumors. The results of in vitro analysis of five human OPSCC cell lines and one human oral tongue squamous cell carcinoma cell line agree with the in vivo trends: low levels of TLR 5 and high levels of TLR 7 in p16-positive OPSCC. Overall, TLR 7 and 9 expression patterns are demonstrated here to relate to the HPV status in vivo and TLR 5 and 7 expression patterns to the p16 status in vivo and in vitro.

Toll‐like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue

BACKGROUND Toll-like receptor 9 (TLR9) is a cellular receptor, which recognizes bacterial and host-derived DNA. Stimulation of TLR9 induces cellular invasion via matrix metalloproteinase 13 (MMP-13). The aim of this study was to evaluate the role of TLR9 in invasion of oral tongue squamous cell carcinoma (OTSCC). METHODS The effects of TLR9 ligands on oral squamous cell carcinoma cell lines were studied with invasion and migration assays, as well as in a myoma organotypic model. RESULTS The TLR9 ligand, CpG-ODN, increased invasion and migration in OTSCC lines. These effects were reduced by TLR9 siRNA or inhibition with TLR9 antibodies. Immunohistochemical analysis of tissues from 195 patients with OTSCC revealed that TLR9 was expressed in 181/195 carcinomas. The expression of TLR9 was higher in the malignant cells than in the normal epithelium. High TLR9 expression was associated with high MMP-13 expression and poor differentiation. High TLR9 expression was also identified as an independent predictor of poor prognosis (HR 1.810, 95% CI [1.053-3.112]). CONCLUSION Toll-like receptor 9 mediates OTSCC invasion and migration in vitro and is an independent prognostic factor of OTSCC. Inhibition of TLR9 may be a novel therapeutic opportunity in oral cancer.