RESUMEN
The progression of genital human papillomavirus (HPV) infections into preneoplastic lesions suggests that infected/malignant cells are not adequately recognized by the immune system. In this study, we demonstrated that cervical/vulvar cancer cells secrete factor(s) that affect both the maturation and function of dendritic cells (DC) leading to a tolerogenic profile. Indeed, DC cocultured with cancer cell lines display both a partially mature phenotype after lipopolysaccharide (LPS) maturation and an altered secretory profile (IL-10high and IL-12p70low). In addition, tumor-converted DC acquire the ability to alter T-cell proliferation and to induce FoxP3+ suppressive T cells from naive CD4+ T cells. Among the immunosuppressive factors implicated in DC alterations in genital (pre)neoplastic microenvironment, we identified receptor activator of nuclear factor kappa-B ligand (RANKL), a TNF family member, as a potential candidate. For the first time, we showed that RANKL expression strongly increases during cervical progression. We also confirmed that RANKL is directly secreted by cancer cells and this expression is not related to HPV viral oncoprotein induction. Interestingly, the addition of osteoprotegerin (OPG) in coculture experiments reduces significantly the inhibition of DC maturation, the release of a tolerogenic cytokine profile (IL-12low IL-10high) and the induction of regulatory T (Treg) cells. Our findings suggest that the use of inhibitory molecules directed against RANKL in cervical/vulvar (pre)neoplastic lesions might prevent alterations of DC functionality and represent an attractive strategy to overcome immune tolerance in such cancers.
RESUMEN
Tumor prognosis is generally defined by various tumor parameters. However, it is well known that paracrine, endocrine and cell-cell interactions between the tumor and its microenvironment contribute to its growth. The tumor microenvironment (TME) can also influence disease prognosis and is likely to be considered as an important prognostic factor. In addition, conventional therapies can influence the microenvironment and antitumor immunity. Similarly, the TME will influence the effectiveness of therapy. The purpose of this review is to demonstrate how TME is important in therapeutic management. Key interactions between TME and different cancer therapies as well as their current clinical consequences have been described. More research is needed to establish the important network between tumor cells and their environment to highlight their relationships with conventional therapies and develop global therapeutic strategies.
Asunto(s)
Neoplasias/terapia , Microambiente Tumoral/fisiología , Animales , Humanos , Neoplasias/inmunología , Neoplasias/patología , Pronóstico , Microambiente Tumoral/inmunologíaRESUMEN
Galectins, a family of endogenous lectins, are multifunctional effectors that act at various sites and can be used in immunohistochemical localization studies of diseased states. Since they form a potentially cooperative and antagonistic network, we tested the hypothesis that histopathological fingerprinting of galectins could refine the molecular understanding of naso-sinusal pathologies. Using non-cross-reactive antibodies against galectin-1, -3, -4, -7, -8 and -9, we characterized the galectin profiles in chronic rhinosinusitis, nasal polyposis, inverted papillomas and squamous cell carcinomas. The expression, signal location and quantitative parameters describing the percentage of positive cells and labeling intensity were assessed for various cases. We discovered that inverted papillomas showed a distinct galectin immunohistochemical profile. Indeed, epithelial overexpression of galectin-3 (p=0.0002), galectin-4 (p<10-6), galectin-7 (p<10-6) and galectin-9 (p<10-6) was observed in inverted papillomas compared to non-malignant diseases. Regarding carcinomas, we observed increased expression of galectin-9 (p<10-6) in epithelial cells compared to non-tumor pathologies. Our results suggest that galectin-3, -4, -7 and -9 could be involved in the biology of inverted papillomas. In addition, we observed that the expression of galectin in naso-sinusal diseases seems to be affected by tumor progression and not inflammatory or allergic phenomena.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Galectinas/metabolismo , Pólipos Nasales/patología , Neoplasias de los Senos Paranasales/patología , Rinitis/patología , Sinusitis/patología , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Niño , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/metabolismo , Papiloma Invertido/metabolismo , Papiloma Invertido/patología , Neoplasias de los Senos Paranasales/metabolismo , Estudios Retrospectivos , Rinitis/metabolismo , Sinusitis/metabolismo , Adulto JovenRESUMEN
Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype in tumorigenesis is still confusing. Constitutively produced or induced in inflammatory conditions, human beta-defensins (HßDs) are cationic peptides involved in host defenses against bacteria, viruses and fungi. Here, we investigated both the role of p63 proteins in the regulation of HßDs and the implication of these antimicrobial peptides in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed that ΔNp63 proteins (α, ß, γ) induce HßD1, 2 and 4 expression. Similar results were observed in cancer tissues and cell lines. We next demonstrated that ΔNp63-overexpressing SCC are associated with both a poor prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we showed that HßDs exert a chemotactic activity for (lymphatic) endothelial cells in a CCR6-dependent manner. The ability of HßDs to enhance (lymph)angiogenesis in vivo was also evaluated. We observed that HßDs increase the vessel number and induce a significant increase in relative vascular area compared to negative control. Taken together, the results of this study suggest that ΔNp63-regulated HßD could promote tumor (lymph)angiogenesis in SCC microenvironment.
Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Linfangiogénesis , Neovascularización Patológica/metabolismo , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Neoplasias del Cuello Uterino/genética , beta-Defensinas/genética , Adulto , Anciano , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/química , Línea Celular Tumoral , Quimiotaxis , Células Endoteliales , Femenino , Genes Supresores de Tumor , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/química , Humanos , Queratinocitos , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Receptores CCR6/metabolismo , Tasa de Supervivencia , Factores de Transcripción/análisis , Factores de Transcripción/metabolismo , Transfección , Microambiente Tumoral , Proteínas Supresoras de Tumor/análisis , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia Arriba , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/química , beta-Defensinas/análisis , beta-Defensinas/metabolismoRESUMEN
We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.
Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Infecciones por Papillomavirus/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , Cetuximab , Quimioradioterapia , Cisplatino/uso terapéutico , ADN Viral/análisis , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae , Infecciones por Papillomavirus/virología , Estudios Prospectivos , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Human papillomavirus (HPV) is implicated in head and neck squamous cell carcinomas. However, the causal role of HPV in carcinomas of the parotid gland remains uncertain and less documented. This study aimed to determine the potential implication of HPV in the development of benign and malignant lesions of the parotid gland. MATERIALS AND METHODS: Paraffin-embedded biopsies were obtained from 40 patients with benign parotid gland tumors and from 39 patients with parotid gland carcinomas. The 79 samples were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus Polymerase Chain Reaction (PCR) and type-specific E6/E7 PCR to detect 18 HPV types. RESULTS: Our results showed a low prevalence of HPV, with only three HPV-positive cases among the 40 benign tumors and one infected carcinoma in the malignant population. CONCLUSION: No association between the presence of HPV DNA and the development of parotid gland tumors was found in our study.
Asunto(s)
Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Infecciones por Papillomavirus/virología , Neoplasias de la Parótida/virología , Adolescente , Adulto , Anciano , Inhibidor p16 de la Quinasa Dependiente de Ciclina , ADN Viral/análisis , ADN Viral/genética , Proteínas de Unión al ADN/genética , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Neoplasias de la Parótida/metabolismo , Neoplasias de la Parótida/patología , Adulto JovenRESUMEN
OBJECTIVES/HYPOTHESIS: The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients. STUDY DESIGN: Retrospective study. METHODS: Paraffin-embedded samples from OSCC patients (n = 162) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus polymerase chain reaction (PCR) and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68. Immunohistochemical staining for p16, p53, and EGFR was also performed. RESULTS: The type-specific E6/E7 PCR demonstrated that 65 of the 147 OSCC patients (44%) presented with high-risk (hr) HPV types and that 38 of the 147 OSCC patients (26%) presented with low-risk (lr) HPV types. Comparable p53 and EGFR expression levels were observed in the hr HPV+ group (41.5% p53+, 92% EGFR+) and the lr HPV+ group (57% p53+, 92% EGFR+). Conversely, a slight increase in the proportion of p16+ tumors was observed in the hr HPV+ group (65%) compared with the lr HPV+ group (44%). In regard to patient outcome, the presence of HPV was correlated with a worse prognosis (P = .007). CONCLUSIONS: A high prevalence of hr and lr HPV infections was detected in the OSCC patients included in the study. Moreover, hr HPV positivity was correlated with a decreased 5-year disease-free survival rate compared with HPV- and lr HPV+.
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Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , ADN Viral , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/virología , Papillomaviridae/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Receptores ErbB/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Proteínas de Neoplasias/biosíntesis , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/biosíntesis , Adulto JovenRESUMEN
The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100% p16+, 56% p53+ and 97% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92% p16+, 66% p53+ and 100% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup.
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Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/epidemiología , Neoplasias Laríngeas/complicaciones , Neoplasias Laríngeas/epidemiología , Papillomaviridae/fisiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Niño , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Receptores ErbB/metabolismo , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiología , Humanos , Incidencia , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/virología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Pronóstico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/metabolismo , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: C-X-C ligand (CXCL) chemokines exert major roles in the biologic aggressiveness of esophageal cancer. In the current study, the authors investigated temozolomide (TMZ)-induced effects on activity of the CXCL chemokine network in human esophageal cancer cells. To the authors' knowledge, TMZ has not been investigated previously in experimental or clinical esophageal cancers. METHODS: A complete mapping of CXCL chemokines and their receptor messenger RNA was performed in 2 established human esophageal cancer cell lines (OE21 and OE33) and in 4 surgical samples from patients with esophageal carcinoma. The analyses pointed out the potential importance of CXCL2, and monitoring CXCL2 with quantitative videomicroscopy indicated that its biologic activity was silenced in OE21 esophageal cancer cells. TMZ-mediated antitumor activity was determined in vivo in an OE21 metastatic nude mice xenograft model. RESULTS: The messenger RNA levels of CXC chemokines and their receptors were similar in both cell lines and in the 4 surgical specimens. CXCL2 depletion by small interfering RNA (siRNA) displayed marked effects on the proliferation of transfected OE21 cells. Chronic in vitro TMZ treatment of OE21 and OE33 cells markedly decreased CXCL2 and CXCL3 secretion. In vivo, TMZ induced significant delays in OE21 xenograft tumor development and improved the survival of OE21 xenograft-bearing mice, whereas cisplatin did not. Analyses performed on tissue samples from in vivo experiments revealed that TMZ also impaired tumor angiogenesis. CONCLUSIONS: The current study emphasized the role of proangiogenic chemokines in esophageal cancer biology and indicated the possibility of using TMZ as a clinically compatible drug to impair the actions of the CXCL chemokine network in esophageal cancers.
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Antineoplásicos Alquilantes/uso terapéutico , Dacarbazina/análogos & derivados , Neoplasias Esofágicas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Dacarbazina/uso terapéutico , Neoplasias Esofágicas/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Ratones Desnudos , Temozolomida , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: The aim of this study was to determine the prevalence of human papillomavirus (HPV) in 80 tumor-free tonsils from healthy children and adults using a sensitive E6/E7 type-specific polymerase chain reaction (PCR). STUDY DESIGN: Cross-sectional study. SETTING: Ear, nose, and throat department, university hospital. SUBJECTS AND METHODS: Paraffin-embedded tissues from tumor-free tonsils (TFTs) were evaluated for HPV DNA using GP5+/6+ consensus PCR and subsequent genotyping using E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68. The immunohistochemical expression of p16 and p53 was also assessed. RESULTS: In 80 TFTs, the authors identified 10 (12.5%) that tested positive for the following high-risk HPV types: HPV 16 (8 cases), 18 (1 case), and 31 (1 case). Twelve patients (15%) tested positive for HPV infection using the GP5+/GP6+ consensus primers but were negative using quantitative PCR. These patients were considered infected with low-risk HPV types. Fifty-eight TFTs (72.5%) tested negative for both GP5+/GP6+ and type-specific HPV PCR analysis (HPV negative). Among patients infected with HPV, the authors observed a slight increase in frequency with age. CONCLUSION: In TFTs, oncogenic and nononcogenic HPVs were present at a relatively high frequency in children and adults. The presence of high-risk HPV DNA in young children supports the horizontal transmission hypothesis and argues in favor of HPV vaccination at birth.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Tonsila Palatina/virología , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Alphapapillomavirus/genética , Bélgica/epidemiología , Niño , Estudios Transversales , ADN Viral/análisis , Humanos , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Prevalencia , Valores de Referencia , Estudios RetrospectivosRESUMEN
AIMS: This study tests the hypothesis that histopathological fingerprinting of galectins, which are emerging multifunctional effectors in cell sociology, could refine the differential diagnosis of salivary tumours. METHODS AND RESULTS: We applied non-crossreactive polyclonal antibodies against galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-7 (Gal-7) and galectin-8 (Gal-8) for immunohistochemical analysis of salivary gland tumours (72 cases with benign disease and 39 cases with malignancy) and 29 control specimens. The principal positivity of cases, the site of signal presence and the quantitative parameters concerning percentage of positive cells and labelling intensity were determined. Acinic cell and adenoid cystic carcinomas (specifically tubular and cribriform types) shared the expression signature of Gal-1, Gal-3 and Gal-8 presence combined with Gal-7 absence. Mucoepidermoid carcinomas presented a unique profile based on cytoplasmic Gal-1, Gal-3, Gal-7 and Gal-8 localization in the intermediate cells. Adenomas were separable from malignancy by a consistent decrease in the labelling index (LI) for Gal-7 and Gal-8 (LI Gal-7, P<10(-6) ; LI Gal-8, P=0.001). When present, staining for the tumour suppressor p16(INK4a) coincided with Gal-1 presence. CONCLUSIONS: Expression profiling of the four tested galectins in salivary gland tumours revealed non-uniform staining patterns with discriminatory potential based on intracellular localization and quantitative aspects.
Asunto(s)
Adenocarcinoma/metabolismo , Galectinas/biosíntesis , Neoplasias de las Glándulas Salivales/metabolismo , Adenocarcinoma/diagnóstico , Adenoma Pleomórfico/diagnóstico , Adenoma Pleomórfico/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antineoplásicos/inmunología , Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/metabolismo , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/metabolismo , Diagnóstico Diferencial , Femenino , Galectinas/inmunología , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/diagnóstico , Adulto JovenRESUMEN
PURPOSE: We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC). METHODS: Paraffin-embedded tumours from HSCC patients (n = 75) were evaluated for p16, p21 and p53 expression by immunohistochemistry. HPV DNA was detected by GP5+/6+ consensus PCR and subsequent genotyping by E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. RESULTS: Among the 61 specimens that tested positive for the ß-globin, HPV typing identified 50 patients with high-risk (hr) HPV types. HPV 16E7 DNA was detected in 74% (37 cases) of these specimens. Twelve patients were found to be infected with multiple HPV types. However, the presence of hrHPV DNA was not found to correlate with the proportion of disease-free patients. The 5-year disease-free survival rate was 73% in p53- tumours versus 48% in p53+ tumours (P = 0.008). CONCLUSION: In our series of patients with stage IV HSCC, the hrHPV+ subgroup had a similar prognosis (in terms of recurrence risk) as the HPV- subgroup. p53 overexpression was associated with a worse prognosis.
Asunto(s)
Carcinoma/diagnóstico , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/diagnóstico , Papillomaviridae/aislamiento & purificación , Proteína p53 Supresora de Tumor/metabolismo , Anciano , Carcinoma/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina , ADN Viral/análisis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Papillomaviridae/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , PronósticoRESUMEN
Warthin's tumor of the parotid gland is assumed to originate from the proliferation of epithelial inclusions within parotid lymph nodes. In that case, these cells are supposed to retain characteristics similar to common salivary gland ductal cells. Using immunohistochemical fingerprinting with four members of the family of adhesion/growth-regulatory galectins and comparison to intra- and interlobular ducts, marked similarities were noted for presence of galectins-3, -7 and -8. Notably, profiles of lectin binding, determined by applying human lectins as probes, were also similar when testing biotinylated galectins-3 and -8. Besides defining the galectin histochemical parameters in Warthin's tumors this study adds support to the hypothesis of heterotopia.
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Adenolinfoma/metabolismo , Galectinas/metabolismo , Neoplasias de la Parótida/metabolismo , Adenolinfoma/etiología , Adenolinfoma/patología , Galectina 1/metabolismo , Galectina 3/metabolismo , Humanos , Inmunohistoquímica , Modelos Biológicos , Neoplasias de la Parótida/etiología , Neoplasias de la Parótida/patología , Mapeo Peptídico , Estudios RetrospectivosRESUMEN
Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years. The worse prognosis of these cancers must certainly be link to the fact that HNSCCs strongly influence the host immune system. We present a critical review of our understanding of the HNSCC escape to the antitumor immune response such as a downregulation of HLA class I and/or components of APM. Antitumor responses of HNSCC patients are compromised in the presence of functional defects or apoptosis of T-cells, both circulating and tumor-infiltrating. Langerhans cells are increased in the first steps of the carcinogenesis but decreased in invasive carcinomas. The accumulation of macrophages in the peritumoral areas seems to play a protumoral role by secreting VEGF and stimulating the neoangiogenesis.