A simple novel prognostic model for early stage oral tongue cancer.

The prognostication of patient outcome is one of the greatest challenges in the management of early stage oral tongue squamous cell carcinoma (OTSCC). This study introduces a simple histopathological model for the prognostication of survival in patients with early OTSCC. A total of 311 cases (from Finland and Brazil) with clinically evaluated early stage OTSCC (cT1-T2cN0cM0) were included in this multicentre retrospective study. Tumour budding (B) and depth of invasion (D) were scored on haematoxylin-eosin-stained cancer slides. The cut-off point for tumour budding was set at 5 buds (low <5; high ≥5) and for depth of invasion at 4mm (low <4mm; high ≥4mm). The scores of B and D were combined into one model: the BD predictive model. On multivariate analysis, a high risk score (BD score 2) correlated significantly with loco-regional recurrence (P=0.033) and death due to OTSCC (P<0.001) in early stage OTSCC. The new BD model is a promising prognostic tool to identify those patients with aggressive cases of early stage OTSCC who might benefit from multimodality treatment.

CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma.

We investigated the expression of CD44 and MMP-9 in primary oral squamous cell carcinoma (OSCC) and evaluated their association with each other and clinicopathological factors as well as their prognostic value during long term follow up. Histological samples from 138 OSCC patients were immunohistochemically stained for the expression of CD44 and MMP-9. The staining results were compared with conventional prognostic factors and their impacts to patients' prognosis were also studied with survival analyses. Irregular staining of CD44 in tumour cells was associated with poor tumour differentiation (p=0.003), higher clinical stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong stromal MMP-9 staining intensity was correlated with poor tumour differentiation (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour cells was related to poor disease free and overall survival (p=0.001 and p<0.001, respectively). In multivariate analysis CD44 staining was a significant independent predictor for overall (p=0.03) and disease free survival (p=0.003). MMP-9 expression showed no statistical significance in survival analyses. Strong stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in tumour cells, but had no prognostic significance in the present cohort. However, irregular staining of CD44 predicted more advanced disease and shortened survival of the patients.

Versican expression in pharyngeal squamous cell carcinoma: an immunohistochemical study.

AIMS: To study the expression of versican, a large proteoglycan involved in repressing adhesion between cells and the extracellular matrix in pharyngeal squamous cell carcinoma (PSCC), and its relation to the expression of p53 and catenins, histological differentiation, clinical data, and prognosis. METHODS: For the retrospective survey, primary tumours for analyses were obtained from 118 patients diagnosed with PSCC of the oropharynx or hypopharynx. The immunohistochemical expression of versican was studied and was related to the expression pattern of p53 and catenins, in addition to clinical data and survival. RESULTS: In the primary tumours, strong stromal versican expression was graded as low in 59 (50%) and high in 59 (50%) cases. In addition, intracellular versican staining was seen in nine (8%) tumours. In local lymph node metastases, strong stromal versican staining was significantly more frequent compared with the primary tumours (p = 0.018). Strong stromal versican staining was more frequently seen in less advanced tumours (p = 0.015). There was no association between versican expression and the other investigated variables (p53, catenins, TNM status, and histological grade). Neither stromal nor intracellular versican expression predicted overall survival in these patients. CONCLUSIONS: Versican was more strongly expressed in the stroma of local metastases and in the earlier stages of disease in PSCC. However, versican expression was not an independent prognostic factor in this entity.

Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma.

Several malignant tumours accumulate hyaluronan (HA), a matrix component suggested to promote cancer cell growth and migration. The expression and prognostic value of HA was analysed in a cohort of 151 oral squamous cell carcinoma (SCC) patients with adequate archival tumour material and follow-up data. The tumour samples were stained using a biotinylated HA-specific probe. Normal squamous epithelium showed a strong and homogeneously distributed staining for HA. The most superficial layers were HA-negative. In moderate (n=11) and high grade (n=16) dysplasias an irregular HA staining was observed around invasive cancer. Malignant transformation in oral squamous cell epithelium changed the staining toward irregular with focal reduction of HA. The well (n=92) or moderately differentiated (n=47) carcinomas had a strong HA staining intensity. In poorly differentiated tumours (n=12) the HA staining was weaker and mainly intracellular. The stromal tissue showed usually moderate (n=69) or strong (n=67) HA staining intensity with no statistically significant correlation with the degree of tumour differentiation. At the end of the follow-up (median 52 months) 66 (43%) patients had died because of an oral SCC. A significant difference in overall survival (OS) and disease free survival (DFS) (P=0.0002 and 0.0020, respectively) was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival. In Cox's multivariate analysis HA staining was a significant independent predictor of OS (P=0.011) and DFS (P=0.013). These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.

Nuclear beta catenin expression is related to unfavourable outcome in oropharyngeal and hypopharyngeal squamous cell carcinoma.

AIMS: To investigate the expression of alpha, beta, and gamma catenins in oropharyngeal and hypopharyngeal squamous cell carcinoma and their relations to each other, as well as to clinical data, tumour differentiation, and prognosis. METHODS: Primary tumours for analysis were obtained from 138 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemistry was used to evaluate the expression of alpha, beta, and gamma catenins. The expression patterns of all catenins were related to clinical data and survival. RESULTS: The expression patterns of all three catenins were significantly interrelated. Reduced gamma catenin expression was significantly associated with poor histological differentiation. No association was found between alpha or beta catenin expression and clinicopathological characteristics. In univariate analysis, patients whose tumours had nuclear beta catenin expression had shorter overall survival than patients with no nuclear expression. In Cox multivariate analysis, nuclear beta catenin expression, tumour status (T class), and Karnofsky performance index were independent prognostic factors of overall survival. CONCLUSIONS: Reduced expression of gamma catenin is associated with dedifferentiation in primary squamous cell carcinoma of the oropharynx and hypopharynx. The fact that nuclear beta catenin expression independently predicts short overall survival suggests that it might be a valuable prognostic marker in pharyngeal squamous cell carcinoma.

Isolated sphenoid sinus diseases: report of 39 cases.

OBJECTIVE: To detail the underlying pathological conditions, symptoms, signs, and outcomes of patients with isolated sphenoid sinus involvement. DESIGN: A retrospective survey. SETTING: An academic referral center of a university hospital. PATIENTS: All 39 patients, aged 7 to 85 years, treated in the Department of Otorhinolaryngology, Kuopio University Hospital, Kuopio, Finland, from 1988 through 1997 for isolated sphenoid sinus disease. RESULTS: Sinusitis was characterized as acute in 26 patients, subacute in 5 (including 1 pyocele), and chronic in 8 (including 2 fungal infections). No tumors were found. Isolated sinus cysts were excluded from the study. Headache, the main symptom in 32 patients (82%), was localized most commonly on the vertex. Other common complaints were rhinitis, dizziness, eye symptoms, and fever. In 2 patients, the finding was occult. Eight patients (21%) presented with cranial nerve deficits, and 1 patient had an intracranial complication. Sinus irrigation was performed in 16 patients (41%) and sphenoidotomy was performed in 10 (26%). Fifteen patients (38%) were treated with antibiotic drugs alone. Within 3 months, 31 (84%) of 37 patients had recovered from the illness; 5 still experienced headaches despite having normalized radiographic findings; and 1 had permanent unilateral visual loss. Two patients were lost to follow-up. CONCLUSIONS: Sphenoid sinus opacity is mostly inflammatory in origin. Despite the benign nature of the disease, there is a risk of complications with high morbidity and mortality. Early and, if necessary, aggressive therapy to guarantee drainage of the sinus is recommended.

Merkel cell carcinoma of the auricle.

Merkel cell carcinoma is a rare, although increasingly recognized, malignant tumor of the skin. The most common site of occurrence is the head and neck (50%). Only five cases of this tumor on the auricle have been reported previously. We present a further such case. The incidence, clinical features, diagnosis, prognosis, and treatment of the Merkel cell carcinoma are discussed.

The "toughening" phenomenon in rat's auditory organ.

In audiological "toughening" or "conditioning" phenomenon prior exposure to moderate noise reduces the extent of hearing deterioration caused by the subsequent exposure to traumatic test noise known to cause inner ear damage. "Toughening" has been demonstrated in many mammalian laboratory animals such as guinea pig and chinchilla but not in rat or mouse. Our aim was to study the occurrence of this phenomenon in the rat. Ninety-one white male Wistar rats were divided into four groups: unexposed control group (U, n = 10), "conditioning" only (C, n = 32), "conditioning" plus test noise (C + T, n = 36) and test noise only (T, n = 13). Groups C and C + T were "conditioned" for 10 hours with 4.0 kHz OBN between 55 and 95 dB sound pressure levels (SPLs). After 10 hours rest groups C + T and T were exposed to the same noise at 105 dB SPL for 13 hours. The hearing thresholds were determined by auditory brainstem response audiometry (ABR) either immediately after or 3 weeks after the exposures. After that the animals were sacrificed. The cochleas were removed and perilymphatically fixed and further processed for quantitative cytocochleograms. Both the temporary (TTS) and the permanent threshold shifts (PTS) were smaller in animals which had been "conditioned" prior exposure to traumatic noise. Yet only 95 dB SPL "conditioning" gave statistically significant difference (p < 0.05) in PTS. From our results we conclude that "conditioning" effect seems to be present also in the rat. However to confirm this, further experiments are needed. The mechanisms behind "conditioning" are still unknown and also to clarify them, further efforts are needed.