Total pharyngolaryngectomy for squamous cell carcinoma of the hypopharynx: A review

Objectives. To evaluate our experience with total pharyngolaryngectomy in the treatment of hypopharyngeal squamous cell carcinoma. Study Design: Retrospective analysis of consecutively treated patients in an academic otolaryngology, head and neck department. Methods. One hundred eighty patients who had total pharyngolaryngectomy performed for hypopharyngeal carcinoma were included in this study. Patients with a history of previous head and neck cancer were excluded. Clinicopathologic parameters were recorded and survival calculated using the Kaplan-Meier method. Results. One hundred sixty-two (90%) of the patients were male, and the patients had a mean age of 62 years. The majority (91%) of patients had advanced overall clinical stage disease (stage 3,4). Thirty-one (17.8%) and 43 (24%) patients developed locoregional and metastatic disease recurrence, respectively. The 2- and 5-year disease-specific survival rates were 72% and 52%, respectively. Advanced nodal stage, perineural invasion, lymphovascular invasion, and positive margins were predictors of poor survival on univariate analysis, and lymphovascular invasion was an independent prognostic factor on multivariate analysis. Conclusion: Surgery and postoperative radiotherapy remains the treatment against which other modalities should be compared for advanced stage hypopharyngeal squamous cell carcinoma.

Correlação da imunoexpressão do fator de choque térmico 1 (hsf1) com aspectos clinicopatológicos em carcinomas de células escamosas de língua oral

Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

Correlação da imunoexpressão do fator de choque térmico 1 (hsf1) com aspectos clinicopatológicos em carcinomas de células escamosas de língua oral

Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

Osteopontin expression correlates with melanoma invasion

Melanoma is one of the most aggressive cancers affecting humans. Although early melanomas are curable with surgical excision, metastatic melanomas are associated with high mortality. The mechanism of melanoma development, progression, and metastasis is largely unknown. In order to uncover genes unique to melanoma cells, we used high-density DNA microarrays to examine the gene expression profiles of metastatic melanoma nodules using benign nevi as controls. Over 190 genes were significantly overexpressed in metastatic melanomas compared with normal nevi by at least 2-fold. One of the most abundantly expressed genes in metastatic melanoma nodules is osteopontin (OPN). Immunohistochemistry staining on tissue microarrays and individual skin biopsies representing different stages of melanoma progression revealed that OPN expression is first acquired at the step of melanoma tissue invasion. In addition, blocking of OPN expression by RNA interference reduced melanoma cell numbers in vitro. Our observations suggest that OPN may be acquired early in melanoma development and progression, and may enhance tumor cell growth in invasive melanoma.

Cell invasion with proliferation mechanisms motivated by time-lapse data

Cell invasion involves a population of cells which are motile and proliferative. Traditional discrete models of proliferation involve agents depositing daughter agents on nearest- neighbor lattice sites. Motivated by time-lapse images of cell invasion, we propose and analyze two new discrete proliferation models in the context of an exclusion process with an undirected motility mechanism. These discrete models are related to a family of reaction- diffusion equations and can be used to make predictions over a range of scales appropriate for interpreting experimental data. The new proliferation mechanisms are biologically relevant and mathematically convenient as the continuum-discrete relationship is more robust for the new proliferation mechanisms relative to traditional approaches.