Matti Pukkila

Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators in early-stage oral tongue cancer

Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early‐stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low‐risk and high‐risk categories would represent a major advancement in their management.

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma

Background: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth. Aims: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation. Methods: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records. Results: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome. Conclusions: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.

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

Aims—To investigate the expression of α, β, and γ 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 α, β, and γ 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 γ catenin expression was significantly associated with poor histological differentiation. No association was found between α or β catenin expression and clinicopathological characteristics. In univariate analysis, patients whose tumours had nuclear β catenin expression had shorter overall survival than patients with no nuclear expression. In Cox multivariate analysis, nuclear β catenin expression, tumour status (T class), and Karnofsky performance index were independent prognostic factors of overall survival. Conclusions—Reduced expression of γ catenin is associated with dedifferentiation in primary squamous cell carcinoma of the oropharynx and hypopharynx. The fact that nuclear β catenin expression independently predicts short overall survival suggests that it might be a valuable prognostic marker in pharyngeal squamous cell carcinoma.

Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression

BackgroundEpithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT.MethodsImmunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.ResultsTumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).ConclusionTWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.

Evolution of Mild Obstructive Sleep Apnea after Different Treatments

Study Objectives: To evaluate the prognosis of mild obstructive sleep apnea in relation to different treatment modalities.

Accuracy of the current TNM classification in predicting survival in patients with sinonasal mucosal melanoma

The first International Union Against Cancer (UICC) TNM classification for aerodigestive malignant mucosal melanoma was not published until 2009, and since then, only a few studies have evaluated the accuracy of this staging system. Our aim was to evaluate the accuracy of this UICC staging system for sinonasal malignant mucosal melanoma (SMMM) in a nationwide survey.

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.

The impact of weight reduction in the prevention of the progression of obstructive sleep apnea: an explanatory analysis of a 5-year observational follow-up trial

BACKGROUND Obstructive sleep apnea (OSA) is a chronic progressive disease, and it is well-documented that severe OSA is associated with an increased cardiovascular morbidity and mortality. Weight reduction has been shown to improve OSA; however, we need further evidence to determine if it may prevent the progression of OSA in the long term. The aim of our study was to assess the impact of weight change during a 5-year observational follow-up of an original 1-year randomized controlled trial. METHODS The participants were divided into the two groups according to the weight change at 5-year follow-up using the 5% weight loss as a cutoff point, which was later referred to as the successful (n = 20) or unsuccessful groups (n = 27). The change in apnea-hypopnea index (AHI) was the main objective outcome variable. RESULTS Fifty-seven patients participated in the 5-year follow-up. At 5 years from the baseline, the change in AHI between the groups was significant in the successful group (-3.5 [95% confidence interval {CI}, -6.1 to -0.9]) compared with the unsuccessful group (5.0 [95% CI, 2.0-8.5]) (P = .002). Successful weight reduction achieved an 80% reduction in the incidence of progression of OSA compared to the unsuccessful group (log-rank test, P = .016). CONCLUSIONS A moderate but sustained weight reduction can prevent the progression of the disease or even cure mild OSA in obese patients.

Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma: Prognostic implications

The role of p53 expression in human neoplasms is still controversial, and it has been associated with both favorable and unfavorable outcome of the patients. Also cytoplasmic expression of p53 protein has been reported to affect survival in some cancers. Furthermore, an association between p53 and β‐catenin expression has been demonstrated. We studied the expression of p53 in a large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its relation to catenin expression, histologic differentiation, clinical data, and prognosis.

Inducible Nitric Oxide Synthase Expression in Pharyngeal Squamous Cell Carcinoma: Relation to p53 Expression, Clinicopathological Data, and Survival†

Objective To investigate the expression of inducible nitric oxide synthase (iNOS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC) and its relation to p53 expression, histologic differentiation, clinical data, and prognosis.