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Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.
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INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cetuximab/uso terapêutico , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fenótipo , Receptor de Morte Celular Programada 1/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
BACKGROUND: We aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance. METHODS: We retrieved 96 HNSCC patients who underwent primary surgery. Real-time quantitative RT-PCR was used to analyze a panel of 42 genes coding for major druggable proteins. Univariate and multivariate analyses were performed to assess the prognostic significance of overexpressed genes. RESULTS: Median age was 56 years [35-78]. Most of patients were men (80%) with a history of alcohol (70.4%) and/or tobacco consumption (72.5%). Twelve patients (12%) were HPV-positive. Most significantly overexpressed genes involved cell cycle regulation (CCND1 [27%], CDK6 [21%]), tyrosine kinase receptors (MET [18%], EGFR [14%]), angiogenesis (PGF [301%], VEGFA [14%]), and immune system (PDL1/CD274 [28%]). PIK3CA expression was an independent prognostic marker, associated with shorter disease-free survival. CONCLUSIONS: We identified druggable overexpressed genes associated with a poor outcome that might be of interest for personalizing treatment of HNSCC patients.
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Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Classe I de Fosfatidilinositol 3-Quinases/genética , Quinase 6 Dependente de Ciclina/genética , Receptores ErbB/genética , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-met/genética , RNA Mensageiro/análise , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
INTRODUCTION: To assess the patient's satisfaction in a day-surgery unit in oncology for a surgical diagnosis or therapeutic act. METHODS: Between October 2013 and February 2014, we conducted a satisfaction survey from the validated questionnaire COPS-D. This questionnaire analyse the patient's stages in the care system, from the preoperative consultation to the return home: 9 stages with 23 items rated 1 (bad) to 5 (excellent). It was sent by postmail 3 weeks after their hospitalization. RESULTS: Four hundred and sixty-seven questionnaires were mailed, with a response's rate to 38% (172/467). Participant's characteristics: 88% are women, 45% are full time workers, 54% of senology. Two-third of the assessments were rated 4 or 5. Five percent were rated 1 or 2. The patient's exit is the least preferred step. The operating room's assessment is the most preferred by patients. Sixty-one percent of participants have written a free comment, 31% are positives, 36% are negatives, and 32% are mixed. The wait was the negative recurrent comment (21%). DISCUSSION: Most participants are very satisfied. Improving the wait before the operation and output is already underway. Studies are now needed to assess the care's safety and the economic aspect of day-surgery.
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Procedimentos Cirúrgicos Ambulatórios/psicologia , Institutos de Câncer , Neoplasias/psicologia , Satisfação do Paciente/estatística & dados numéricos , Centros Cirúrgicos , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/cirurgia , Salas Cirúrgicas , Fatores de TempoRESUMO
Cancers of the upper aerodigestive tracts are the fourth most common cancer in France. The main risk factors are smoking and alcohol. They do not necessarily present specific signs, making their early diagnosis difficult. A change in the patient's general condition is a late sign leading to a poor prognosis of the disease.
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Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Feminino , França/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Fatores de RiscoAssuntos
Neoplasias de Cabeça e Pescoço/terapia , Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imunoterapia , Microcirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Infecções por Papillomavirus/complicações , Vacinas contra PapillomavirusRESUMO
Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56(bright) NK cells among CD45(+) hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56(bright)CD16(+) NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN-derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node-positive melanoma.
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Células Matadoras Naturais/imunologia , Linfonodos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Antígeno CD56/imunologia , Antígeno CD56/metabolismo , Citotoxicidade Imunológica/imunologia , Feminino , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Excisão de Linfonodo , Linfonodos/citologia , Linfonodos/patologia , Metástase Linfática , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/patologia , Melanoma/cirurgia , Receptores de IgG/imunologia , Receptores de IgG/metabolismoRESUMO
The objective was to assess the feasibility and safety of transoral robotic surgery (TORS)-assisted free flap reconstruction for hypopharyngeal carcinoma after radiation therapy. The study evaluated the feasibility, surgical margins, the need for a tracheotomy, a nasogastric tube as well as surgery-related complications. Two patients underwent TORS-assisted free flap reconstruction after radiation therapy. The resection margins were free of tumor in both patients. A tracheotomy was performed in one patient who had been decannulated on the sixth postoperative day. One patient resumed satisfactory oral feeding in the fourth postoperative month and the second patient on postoperative day 7. No intraoperative complication and one postoperative complication (neck hematoma) were reported. After a follow-up period of 24 and 30 months, no local recurrence was observed. TORS is feasible for hypopharyngeal resection and assisted free flap reconstruction after radiation therapy. It represents a further step in the development of minimally invasive surgery for the treatment of head and neck cancers with laryngeal preservation.
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Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico/cirurgia , Neoplasias Hipofaríngeas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos de Cirurgia Plástica/métodos , Robótica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
INTRODUCTION: Surgery of extensive skull base tumour results of a defect of soft and hard tissue and dura. Free flap reconstruction provides tissue to restore the defect and separate the intracranial content from the bacterial flora of the nasal fossae. Vertical and transverse rectus abdominis myocutaneous free flap are usually used. This study was designed to compare our experience of latissimus dorsi free flap reconstruction of extensive skull base defects after tumour resection with the literature concerning the use of other types of free flaps. MATERIAL AND METHOD: All extensive skull base tumour resections with latissimus free flap reconstruction made in the head and neck oncology unit of the Institut Curie, Cancer Centre, between January 2004 and December 2009 were reviewed. RESULTS: Two infectious complications were observed (11.7%), two cases of CSF leak (11.7%), one case of wound dehiscence following tumour resection comprising the nasal skin (5.9%) and one case of partial distal necrosis of the flap in a zone of skin resection (5.9%) were observed. No flaps were lost. Two latissimus dorsi donor site haematomas were observed (11.7%). CONCLUSION: When reconstruction of extensive skull base defect need free flap, the latissimus dorsi free flap is a reliable solution.
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Retalhos de Tecido Biológico , Músculo Esquelético/transplante , Procedimentos de Cirurgia Plástica/métodos , Neoplasias da Base do Crânio/cirurgia , Base do Crânio/cirurgia , Adolescente , Adulto , Idoso , Artéria Carótida Externa , Criança , Feminino , Seguimentos , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Veias Jugulares , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Transplante de Pele , Adulto JovemRESUMO
AIMS: Metallothionein (MT) has been implicated in several aspects of cancer pathobiology, such as differentiation, proliferation, apoptosis and invasion. The aim of the present study was to evaluate the clinical significance of MT expression in mobile tongue squamous cell carcinoma (SCC). METHODS AND RESULTS: MT protein expression was assessed immunohistochemically on 49 mobile tongue SCC specimens, and was analysed in relation to clinicopathological characteristics, and overall and disease-free patient survival. All of the examined mobile tongue SCC cases showed MT positivity in tumour cells; however, neither MT overexpression nor staining intensity was significantly associated with clinicopathological parameters. MT cellular distribution was significantly associated with histopathological grade of differentiation and depth of invasion (P = 0.0188 and P = 0.0484, respectively). MT staining intensity was identified as a significant predictor of overall patient survival at both univariate (P = 0.0377) and multivariate (P = 0.0472) levels. Twenty-seven (55.10%) of the examined SCC cases showed MT positivity in squamous tongue epithelium adjacent to the tumour, the MT positivity being correlated with depth of invasion (P = 0.0281), vascular invasion (P = 0.0194), and the existence of lymph node metastases (P = 0.0194). CONCLUSIONS: MT may be implicated in the development and progression of mobile tongue SCC and could be considered as a useful clinical marker for patient management and prognosis.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Metalotioneína/biossíntese , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Língua/mortalidadeRESUMO
The prevalence of metastatic basal cell carcinoma (MBCC) varies between 0.0028% and 0.55% of all cases. In total, more than 300 MBCC have been reported in the literature. We report the case of a 72 year old lady, who presented in September 2009 with a 10-year history of a progressively growing, giant, facial basal cell carcinoma (BCC). Clinical and imaging evaluations identified large local invasion with bone and meningeal involvement. Treatment consisted of an extensive surgery including left eye exenteration and meningeal resection followed by radiotherapy. A solitary lung metastasis was identified five months after the primary tumor resection. As the lesion remained solitary but had increased in size five months later, the patient finally accepted a surgical resection. A right upper-lobe pneumonectomy was performed and pathologic examination confirmed the metastasis as a MBCC.
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Carcinoma Basocelular/secundário , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Pulmonares/secundário , Neoplasias Cutâneas/patologia , Nódulo Pulmonar Solitário/secundário , Idoso , Carcinoma Basocelular/patologia , Progressão da Doença , Feminino , Testa/patologia , Osso Frontal/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Metástase Linfática , Imageamento por Ressonância Magnética , Invasividade Neoplásica , Exenteração Orbitária , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that has been considered to play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. The present study aimed to evaluate the clinical significance of RCAS1 expression in mobile tongue squamous cell carcinoma (SCC). MATERIAL/METHODS: RCAS1 protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples obtained from an equal number of patients and was statistically analyzed with clinicopathological characteristics and overall and disease-free patients' survival. RESULTS: Enhanced RCAS1 expression was significantly associated with reduced depth of invasion (p=0.0069), low mitotic index (p=0.0251) and no evidence of muscular invasion (p=0.0098). A borderline association between RCAS1 expression and stromal inflammatory reaction was also noted (p=0.0660). RCAS1 expression was not associated with overall and disease-free survival. CONCLUSIONS: Our data support evidence for possible implication of RCAS1 at the early stage of tumor progression in mobile tongue SCC, whereas the survival prediction using RCAS1 expression as a clinical marker seems uncertain for this type of malignancy.
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Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias da Língua/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias da Língua/patologiaRESUMO
BACKGROUND: Histone deacetylases (HDACs) have been associated with tumor development and progression in several types of human malignancy and HDAC inhibitors are currently being explored as anti-cancer agents in clinical trials. The aim of the present study was to evaluate the clinical significance of HDAC-1 and -2 protein expression in mobile tongue squamous cell carcinoma (SCC). METHODS: HDAC-1 and -2 protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. RESULTS: HDAC-1 overexpression was significantly associated with younger patients' age (P = 0.0381) and male gender (P = 0.0345), poor histopathological grade of differentiation (P = 0.0236) and the presence of lymph node metastases (P = 0.0104). Intense HDAC-1 staining intensity was significantly associated with male gender (P = 0.0127), increased stromal infiltration reaction (P = 0.0125) and well-defined shape of tumor invasion (P = 0.0396). HDAC-2 overexpression did not show significant correlations with any clinicopathological parameters, whereas intense HDAC-2 staining intensity was significantly associated with the presence of muscular invasion (P = 0.0466) and advanced depth of invasion (P = 0.0251). Mobile tongue SCC patients with HDAC-1 overexpression presented shorter overall and disease-free survival compared to those with no evidence of HDAC-1 overexpression (log-rank test, P = 0.0651 and 0.0247, respectively). CONCLUSIONS: The present study supported evidence that HDACs may participate in the formation and progression of mobile tongue SCC, reinforcing their possible use as biomarkers as also the therapeutic utility of HDAC inhibitors in mobile tongue SCC chemoprevention and treatment.
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Carcinoma de Células Escamosas/patologia , Histona Desacetilase 1/análise , Histona Desacetilase 2/análise , Neoplasias da Língua/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/secundário , Tecido Conjuntivo/patologia , Intervalo Livre de Doença , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Fatores Sexuais , Taxa de Sobrevida , Língua/patologia , Neoplasias da Língua/enzimologiaRESUMO
Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4(+) and CD8(+) TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8(+) TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.
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Antígenos CD/fisiologia , Proteínas Reguladoras de Apoptose/fisiologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Receptores de Antígenos de Linfócitos T/fisiologia , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Proteínas Reguladoras de Apoptose/análise , Antígeno B7-1/análise , Antígeno B7-H1 , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Proteína 2 Ligante de Morte Celular Programada 1 , Receptor de Morte Celular Programada 1 , Estudos Prospectivos , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: There is no consensus regarding the therapeutic utility of sentinel lymph node biopsy (SLNB) versus that of nodal observation (NO) in melanoma. OBJECTIVE: To prospectively evaluate a standardized counseling procedure and its effect on patient choices to undergo SLNB or NO. METHODS: In four centers, patients with melanoma eligible for SLNB or NO received a complete counseling procedure that included verbal information from dermatologists and surgeons, a detailed information sheet, and a written consent form. Data collected included patient and tumor characteristics, counseling conditions, and specialties of informing doctors. Factors influencing patients' choices were studied using multivariate analysis. RESULTS: Of 343 consecutive patients, 309 were offered SLNB and NO and received complete verbal and written information from a dermatologist alone (62%) or in association with a surgeon (38%). Approximately half took advice from trusted persons, and half asked for additional time before making a decision; 268 (86.7%) ultimately decided to undergo SLNB. Multivariate analysis showed that older patients, those with a head and neck melanoma, and those informed without a surgeon present were more likely to prefer NO. CONCLUSIONS: This counseling procedure was easily implemented in clinical practice. Patients favored SLNB but were able to understand uncertainties and express preferences.
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Melanoma/psicologia , Melanoma/secundário , Aceitação pelo Paciente de Cuidados de Saúde , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Aconselhamento Diretivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Educação de Pacientes como Assunto , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor, implicated in various aspects of cancer biology, such as differentiation, proliferation, invasion and angiogenesis. The present study aimed to evaluate the clinical significance of PPAR-γ in mobile tongue squamous cell carcinoma (SCC). METHODS: PPAR-γ protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples obtained from an equal number of patients. PPAR-γ expression and intensity of immunostaining were statistically analyzed in relation with clinicopathological characteristics, mitotic index and patients' survival. RESULTS: Elevated PPAR-γ expression was more frequently observed in patients with reduced depth of invasion (P = 0.0111). Moderate/intense PPAR-γ staining intensity was more frequently observed in patients with no evidence of muscular infiltration (P = 0.0229) and reduced depth of invasion (P = 0.0176). Mobile tongue SCC patients presenting enhanced PPAR-γ expression had significantly longer overall and disease-free survival times compared to those with low PPAR-γ expression (log-rank test, P = 0.0162 and P = 0.0114, respectively). CONCLUSIONS: PPAR-γ immunoreactivity in mobile tongue SCC was correlated with clinicopathological characteristics crucial for patients' management and prognosis. PPAR-γ may be considered as a useful prognostic marker in mobile tongue SCC and a potential therapeutic target for tongue cancer chemoprevention and treatment.
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Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidade , PPAR gama/análise , Neoplasias da Língua/química , Neoplasias da Língua/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glossectomia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgiaRESUMO
BACKGROUND: DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, minimizing cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma (SCC). METHODS: MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. RESULTS: MSH2 expression was significantly associated with depth of invasion (P=0.0335), tumor shape (P=0.0396) and muscular invasion (P=0.0098). MLH1 expression was significantly associated with lymph node metastases (P=0.0484) and borderline with perineural invasion (P=0.0699). MGMT expression was significantly associated with depth of invasion (P=0.0472), tumor shape (P=0.0187), perineural invasion (P=0.0115) and lymph node metastases (P=0.0032) and borderline with vascular invasion (P=0.0755). MSH2 expression was significantly associated with disease-free patients' survival in univariate analysis (P=0.0441), being also identified as an independent prognostic factor in multivariate analysis (P=0.0451). CONCLUSIONS: The present study supported evidence for possible implication of MSH2, MLH1 and MGMT proteins in the formation and progression of mobile tongue SCC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/análise , Carcinoma de Células Escamosas/patologia , Metilases de Modificação do DNA/análise , Enzimas Reparadoras do DNA/análise , Reparo do DNA/genética , Proteína 2 Homóloga a MutS/análise , Proteínas Nucleares/análise , Subunidades Proteicas/análise , Neoplasias da Língua/patologia , Proteínas Supressoras de Tumor/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Núcleo Celular/patologia , Progressão da Doença , Intervalo Livre de Doença , Epitélio/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Leucócitos Mononucleares/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Proteína 1 Homóloga a MutL , Invasividade Neoplásica , Fatores Sexuais , Taxa de Sobrevida , Língua/patologiaRESUMO
BACKGROUND: Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. METHODS: Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. RESULTS: Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. CONCLUSION: Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/imunologia , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Inflamação/patologia , Linfócitos do Interstício Tumoral , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Células Estromais/patologia , Neoplasias da Língua/imunologiaRESUMO
The French national health insurance reimbursement system has recently changed from a global hospital funding system to casemix-based funding. The authors studied the factors likely to influence the length of hospital stay for free flap reconstructions after surgery for cancers of the oral cavity or pharynx. Data concerning 207 oral cavity or pharynx free flap reconstructions were extracted from a prospective registration. Lengths of hospital stay were compared by an analysis of variance F test or a nonparametric Kruskal-Wallis test, and transfusion rates were compared by Chi-square test or Fisher's exact test, as appropriate. The median length of hospital stay was 24 days (range: 7-145 days). Length of hospital stay was significantly longer according to the type of flap (p<0.005), in N2-N3 patients (p<0.02), a PINI score more than 10, a 3-4 American Society of Anesthesiologists (ASA) score, the presence of a tracheotomy and in patients requiring transfusion (p<0.0001). As the nodal status, the American Society of Anesthesiologists (ASA) score of the patient, the need of tracheotomy and the type of flap cannot be corrected, the management of preoperative haemoglobin and nutritional status are the sole factors which can improve the length of hospital stay. In the context of the new casemix-based funding, this study raises the problem of harvesting of the fibula flap, management of preoperative haemoglobin and nutritional status.