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.

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. STUDY DESIGN: A retrospective survey. METHODS: Primary tumors for analyses were obtained from 118 patients diagnosed with SCC of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemical analysis was used to evaluate the expression of iNOS and p53. The expression pattern of iNOS was related to p53 expression, clinical data, and survival. RESULTS: High iNOS score was associated significantly with high nuclear p53 expression index (P = .006) and positive cytoplasmic p53 expression (P = .025). The score for iNOS expression was significantly lower in the largest (T4) tumors (P = .043). No association was seen between iNOS score and N or M class, tumor stage, or histologic differentiation. The score for iNOS expression was not related to overall survival. CONCLUSIONS: The expressions of iNOS and p53 seem to be inter-related in pharyngeal SCC, although the causality remains to be clarified. The expression of iNOS shows no prognostic value in pharyngeal SCC.

Homozygous M34T mutation of the GJB2 gene associates with an autosomal recessive nonsyndromic sensorineural hearing impairment in Finnish families.

CONCLUSION: The genetic and audiological data support the hypothesis that the p.M34T is a pathogenic mutation in the Finnish population. The p.M34T mutation displays an autosomal recessive pattern of inheritance and is associated with mild to moderate nonsyndromic sensorineural hearing impairment (SNHI) in the homozygous state. The audiograms often display a hearing impairment notch at 2-4 kHz in young patients, which may aid in the early diagnosis. OBJECTIVES: The aim of the study was to assess whether the p.M34T mutation in the GJB2 gene may associate with nonsyndromic SNHI. METHODS: We systematically reviewed the families with children diagnosed with nonsyndromic SNHI caused by a homozygous p.M34T mutation at the Kuopio and Oulu University Hospital Clinics. The children were re-examined and audiological and genetic data were obtained from their parents and healthy siblings to study genotype-phenotype correlation. RESULTS: We describe 11 patients from 6 families including 5 sibling pairs from 6 to 23 years of age with homozygous p.M34T genotype all having mild nonsyndromic SNHI. In addition, we found three patients with compound p.M34T mutation also exhibiting mild to moderate SNHI.

Reduced gamma-catenin expression and poor survival in oral squamous cell carcinoma.

OBJECTIVE: To investigate whether reduced expression of alpha-, beta-, or gamma-catenin predicts poor survival in oral squamous cell carcinoma (OSCC). DESIGN: Immunohistochemical analyses of a retrospective cohort. SETTING: University-affiliated hospital. PATIENTS: One hundred twenty-four patients with OSCC. MAIN OUTCOME MEASURE: The prognostic value of gamma-catenin expression on disease-specific survival in different T and N category groups in patients with OSCC. RESULTS: Reduced expression of gamma-catenin correlated with poor tumor differentiation of OSCC (P = .04). Patients with reduced gamma-catenin expression in the primary tumor had significantly more frequent lymph node metastasis than did patients with normal gamma-catenin expression (P = . 03). Reduced expression of gamma-catenin (004) but not of alpha-catenin (P = .25) or beta-catenin (P = .48) correlated with poor clinical outcome. Reduced gamma-catenin expression predicted poor disease-specific survival also in the 92 patients with T1 or T2 tumors (P = . 02). In multivariate analysis, advanced T category (P = . 04), neck lymph node metastases (P = . 01), and reduced gamma-catenin expression (P = . 05) were independently related to poor survival. CONCLUSIONS: Reduced expression of gamma-catenin was associated with poor differentiation of OSCC, with neck lymph node metastases, and, more importantly, with poor disease-specific survival. Loss of gamma-catenin expression seems to contribute to metastatic properties of OSCC. Evaluation of the expression pattern of gamma-catenin may be useful for predicting outcome in patients with OSCC.

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

BACKGROUND: 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 beta-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. METHODS: Primary tumors for analyses were obtained from 123 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 p53 as well as alpha-, beta-, and gamma-catenins. RESULTS: In the primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%), intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses (Kaplan-Meier), hypopharyngeal primary site (p =.02), high T class (p <.0005), presence of distant metastases (p =.02), low Karnofsky performance index (p <.0005), high nuclear p53 expression index (p =.01), and positive cytoplasmic p53 expression (p =.04) predicted poorer overall survival (OS). In Cox proportional hazards model, only T class (p =.0005), Karnofsky performance index (p =.005), and nuclear beta-catenin expression (p =.038) predicted poorer OS. CONCLUSION: Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). However, unlike more traditional variables, p53 expression is not an independent predictor of disease outcome in PSCC.