The role of CSE1L expression in cervical lymph node metastasis of larynx tumors / O papel da expressão de CSE1L na metástase em linfonodos cervicais de tumores laríngeos

Abstract Introduction: According to international reports, 30-40% of all head and neck cancers are larynx cancers, comprising 1-2.5% of all cancer types. Cervical nodal involvement has been reported to be 40% and 65% in T3 and T4 cases, respectively. Five-year survival in patients with cervical lymph node metastasis has been demonstrated to be 50% lower compared to patients with no metastasis. Chromosome segregation like 1 protein; is a DNA fragment isolated by Brinkmann et al. in 1995 that corresponds to yeast chromosome segregation protein. Studies on the effect of chromosome segregation like 1 protein expression in head and neck tumors are rare and it has been shown that nuclear chromosome segregation like 1 protein is over-expressed in these studies where gastrointestinal and breast tumors over-expressed cytoplasmic chromosome segregation like 1 protein. Objective: Chromosome segregation like 1 protein may regulate the proliferation and metastasis of T3-T4 glottic larynx cancer. The aim of this study is to show the relationship between chromosome segregation like 1 protein expression and cervical lymph node metastasis of T3-T4 glottic larynx cancer. Methods: A total of 57 male patients who were operated for T3-T4 glottic cancer in a tertiary referral hospital was included in this study. There were 28 patients with cervical lymph node metastasis and 29 patients without lymph node metastasis. Immunohistochemistry was carried out on formalin-fixed, paraffin-embedded archival glottic larynx tumour tissue. According to the percentage of immunoreactive cells, chromosome segregation like 1 protein status was analyzed. Results: Among the patients, who had no cervical lymph node metastasis, 15 patients showed weak nuclear staining, 12 patients showed moderate nuclear staining and only 2 patients showed high nuclear staining for chromosome segregation like 1 protein. Among the patients who had cervical lymph node metastasis, 18 patients showed high nuclear staining, 9 patients showed moderate staining and only one patient showed weak staining for chromosome segregation like 1 protein. None of the metastatic patients showed cytoplasmic staining and only one patient in the non-metastatic group showed cytoplasmic staining for chromosome segregation like 1 protein. There was a positive correlation between nuclear chromosome segregation like 1 protein expression and cervical lymph node metastasis (r = 0,668) and it was statistically significant (p < 0,001). Conclusion: Chromosome segregation like 1 protein expression is correlated with lymph node metastasis in T3-T4 glottic cancers. This may change the approach to cervical node treatment in patients with glottic cancers in future.

Resumo Introdução: De acordo com relatos internacionais, 30% a 40% de todos os casos de câncer de cabeça e pescoço são na laringe, compreendem 1% a 2,5% de todos os tipos de câncer. O envolvimento linfonodal cervical foi relatado em 40% e 65% nos casos T3 e T4, respectivamente. A sobrevida em cinco anos em pacientes com metástase linfonodal cervical demonstrou ser 50% menor em comparação com os pacientes sem metástase. A proteína chromosome seg-regation like 1 é um fragmento de DNA isolado por Brinkmann et al. em 1995 que corresponde à proteína de segregação cromossômica de levedura. Estudos sobre o efeito da expressão da proteína chromosome segregation like 1 em tumores de cabeça e pescoço são raros e os poucos estudos demonstram que a proteína chromosome segregation like 1 nuclear é superexpressa no núcleo, enquanto tumores gastrointestinais e de mama superexpressam a proteína chromosome segregation like 1 citoplasmática. Objetivo: A proteína chromosome segregation like 1 pode regular a proliferação e metástase do câncer glótico de laringe T3-T4. O objetivo deste estudo é mostrar a relação entre a expressão da proteína chromosome segregation like 1 em metástase de linfonodo cervical no câncer glótico de laringe T3-T4. Método: Foram incluídos neste estudo 57 pacientes do sexo masculino submetidos a cirurgias por câncer glótico T3-T4 em um hospital terciário. Havia 28 pacientes com metástase de linfonodos cervicais e 29 pacientes sem metástase linfonodal. A análise imunohistoquímica foi realizada em tecido de tumor glótico de laringe embebido em parafina e fixado em formol. De acordo com a porcentagem de células imunorreativas, analisou-se a expressão da proteína chromosome segregation like 1. Resultados: Entre os pacientes, que não tinham metástase linfonodal cervical, 15 apresentaram coloração nuclear fraca, 12 apresentaram coloração nuclear moderada e apenas 2 apresentaram coloração nuclear elevada para proteína chromosome segregation like 1. Entre os pacientes que apresentavam metástase linfonodal cervical, 18 pacientes apresentaram coloração nuclear elevada, 9 apresentaram coloração moderada e apenas um paciente apresentou coloração fraca. Nenhum dos pacientes com metástase apresentou coloração citoplasmática e apenas um paciente no grupo não-metastático mostrou coloração citoplasmática para a proteína chromosome segregation like 1. Houve uma correlação positiva entre a expressão nuclear da proteína chromosome segregation like 1 e a metástase de linfonodo cervical (r = 0,668), que foi estatisticamente significante (p < 0,001). Conclusão: A expressão da proteína chromosome segregation like 1 está correlacionada com metástases linfonodais em casos de câncer glótico T3-T4 e isso pode mudar a abordagem do tratamento cervical de câncer glótico no futuro.

The prognostic factors for clinical N1b patients in thyroid papillary carcinoma

Background: The aim of this study is to determine the prognostic factors which affect both disease-free survival (DFS) and overall survival (OS) in thyroid papillary carcinoma with clinical lateral lymph node metastasis. Methods: One hundred and three papillary thyroid carcinomas diagnosed in adult patients received therapeutic lateral neck dissection between December 1989 and June 2010 were analyzed retrospectively. All of the patients were classified as American Thyroid Association (ATA) intermediate risk category. Age, gender, tumor stage and size, multicentricity and bilaterality, vascular invasion and extrathyroidal invasion, ipsilateral/contralateral lymph node involvement, lymph node ratio, extranodal tumor extension, and development of recurrence were the factors which might affect disease-free and OS. Univariate and multivariate analyses were performed. ROC analysis was used to find the cutoff value for lymph node ratio. Results: One hundred and three patients were followed median 101 months. Locoregional or systemic recurrence developed in 20 patients (19.4%) while 7 patients (6.8%) had persistent disease. In multivariate analysis, lymph node ratio (P = 0.003, relative risk [RR] 5.4, 95% confident interval [CI] 1.7–16.5) and contralateral lymph node involvement (P = 0.02, RR 4.9, 95% CI 1.3–18.5) were the independent factors affecting DFS where contralateral lymph node involvement (P = 0.009, RR 44.4, 95% CI 2.5–765.2) was the only factor which affected OS. Conclusions: Lymph node ratio and contralateral metastasis affect DFS while contralateral metastases only affect OS in patients with N1b thyroid papillary carcinoma