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Topoisomerase IIβ binding protein 1 (TopBP1), a multiple-BRCT-domain, protein plays crucial roles in chromosome replication, DNA damage repair, apoptosis, and cell cycle checkpoint signalling. The aim of this study was to identify five SNPs at loci potentially located in the 3′UTR region of the TopBP1 gene (rs185903567, rs116645643, rs115160714, rs116195487, rs112843513), their relationship with the risk of squamous cell laryngeal cancer (SCLC), tumor invasiveness, and prognosis. Genotyping was performed in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Allele-specific TopBP1 mRNA and protein expressions were determined by using real-time PCR and Western blotting techniques, respectively. LOH in BRCA1/BRCA2 was determined by using microsatellite markers. Compared to homozygous common allele carriers, heterozygosity for the T variant was associated with increased risk of SCLC (adjusted odds ratio [OR] = 9.83, 95 % confidence interval [CI]: 3.12-22.16, p < 0.0001). The presence of risk allele at rs115160714 TopBP1 determined a higher incidence of nodal metastases (OR = 7.98, 95 % CI: 3.94-16.00, p = 0.001) and higher tumor grade (OR = 6.48, 95 % CI: 0.86-48.01, p = 0.03). The heterozygotes displayed diffuse tumor growth with no distinct borderline (OR = 3.10, 95 % Cl: 0.92-10.62, p = 0.049) and higher depth of invasion (OR = 2.66, 95 % Cl: 0.78-9.03, p = 0.04). Relationships were also identified between TopBP1 mRNA/protein expression and overall survival ( p < 0.0001). The incidence of LOH in BRCA1/BRCA2 was significantly related to higher tumor grade and TFG ( p < 0.05). The results of this study suggest that rs115160714 TopBP1 may be a genetic marker of etiology and progression in laryngeal cancer. [ABSTRACT FROM AUTHOR]

Aim of the study: Expression of EP2 protein, the prostaglandin E2 (PGE2) receptor, produced by tumour microenvironment inflammatory cells as well as tumour cells, may promote cellular proliferation and growth in an autocrine and paracrine fashion. The phenomenon involving these proteins is regulated by interleukin 1β (IL-1β). Many researchers indicate a connection of EP2 and IL-1β in various types of neoplasms with higher tumour progression and poor prognosis. The aim of this study was to analyse the EP2 expression within laryngeal carcinoma tissue and IL-1β levels in peripheral blood mononuclear cell supernatants and to find relationships between clinicomorphological features. Material and methods: A group of 50 patients with verified squamous cell laryngeal carcinoma was analysed in this study. The pathological evaluation included pTNM depth of invasion according to tumour front grading criteria. Immunohistochemical analysis for membranous staining of EP2 in tumour tissues was used. The IL-1β expression was determined by enzyme- linked immunosorbent assay (ELISA). Results: Increased EP2 expression in carcinoma cells was confirmed for more advanced tumours (pT3-pT4 vs. pT1-pT2, p < 0.0001 and pN1-3 vs. pN0, p = 0.02). Tumours with the highest aggressiveness identified by deeper invasion of submucosa or cartilage were characterised by the highest expression of EP2 (p < 0.0001). In laryngeal carcinomas characterised by a lower differentiation the highest EP2 expression in tumour cells was noted (p = 0.009). A positive relationship between IL-1β expression and the presence of lymph node metastases was also confirmed (p = 0.04). Conclusions: The study indicates the potential effect of EP2 receptor and IL-1β on tumour progression in laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

Introduction. Presence of stabilized and activated form of ß-catenin in tumor tissue is connected with increased tumor progression through activation of c-erbB-2 and c-Myc oncogene and epithelial-mesenchymal transition (EMT). Aim. To assess gene and protein expression of ß-catenin in the tumor tissues of laryngeal squamous cell carcinoma and to analyze relationships between this expression on the degree of aggressiveness of the tumor. Material and methods. A group of 71 patients with squamous cell carcinoma of the larynx was analyzed. The pathological evaluation comprised pTNM classification, degree of carcinoma invasion according to tumor front grading criteria. Quantitative analysis of the amplified product in real time (real-time RT-PCR) were used for estimation of mRNA ß-catenin expression in tumor cells. The level of protein expression was determined by Western blot analysis. Results. Increased mRNA ß-catenin expression in cells of laryngeal carcinoma was confirmed in more advanced tumors pT3-4 (p=0.003). Tumors with higher aggressiveness identified by the classification criteria TFG were characterized by higher expression of ß-catenin gene (p=0.002). Deep invasion and disperse infiltration were shown to be related to higher mRNA ß-catenin expression in tumor cells (p=0.01 and p=0.003, respectively). Conclusions. The study indicates a significant role of ß-catenin in determination of aggressiveness of tumor changes in laryngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Introduction. CCR3 (CD193), C-C chemokine receptor type 3 is a receptor that is highly expressed in eosinophils and basophils, and is also detected in Th cells, as well as in airway epithelial cells. Nevertheless, little is known about the function of chemokine receptors in the development and progression of laryngeal cell carcinoma. Aim. The aim of this study was to analyze the expression of CCR3 in peripheral blood mononuclear cells, on the gene and protein level, and to find links with clinical and morphological characteristics (pT, depth and type of invasion) in the carcinoma of the larynx. Material and methods. The analysis included a group of 71 patients with confirmed laryngeal carcinoma. pTNM and TFG classification criteria were applied for the pathological assessment. The expression of markers in the blood cells of patients was assessed using the RT-PCR and Western blot techniques. Results. Increased expression of CCR3 in peripheral blood mononuclear cells (PBMC) was an indicator of advanced tumours evaluated on the basis of the characteristics of pT (pT3-4). Tumours at the highest stages of progression identified by TFG criteria (TFG3-4) were associated with higher expression of CCR3 in PBMC of the studied group of patients. In laryngeal carcinomas characterized by deep invasion with cartilage infiltration, the CCR3 expression was shown to be higher, as well. Conclusions. The study proves the importance of the CCR3 expression in T lymphocytes as an indicator of advanced changes and progression in patients with laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

The role of interactions between tumor cells and autologous immunocompetent cells, the impact on the modulation of the activity of T CD4+ and CD8+ lymphocytes, as well as the influence on the regulation and determination of antitumor cellular immune response in patients with head and neck squamous cell carcinomas (HNSCC) is not completely clear. The aim of this study was to analyze early and late activation antigens expression on T cells subpopulations modified under the influence of the presence of cancer cells to investigate the regulatory mechanisms of the local cellular immune response in carcinoma of the larynx. Cytofluorymetric analysis of the early (CD69+, CD71+) and late activation markers (CD25+high, CD26+, HLA/DR+) expression on T CD3+CD4+ and CD3+CD8+ cells subpopulations in mixed cellular cultures of freshly isolated tumor cells (MLTMC) and non-cancerous normal epithelial cells (MLNCC) with immunocompetent cells was performed in 55 cases of squamous cell laryngeal carcinoma. The whole peripheral blood concentrations of IL-10 and IFN-γ in 21 h and 72 h of experiments were also measured by ELISA. The relationships between the activation markers expression depending on the type of cells used in co-cultures, as well as the level of secreted cytokines, were investigated. Our work has revealed a statistically significant dependence of cytofluorymetricresults on the presence of TMC or NCC in mixed cellular cultures. Increased expression of CD69+, CD71+ and CD25+ high, CD26+, HLA/DR+ antigens on T CD3+CD4+ and CD3+CD8+ cells was higher in MLTMC cultures, in comparison with MLNCC. We demonstrated negative significant relationships of IFN-γ and IL-10 secretion with regard to CD4+CD69+, CD8+CD69+, CD4+CD71+, CD8+CD71+ antigens expression in 21 h of experiments without mitogenic stimulation. Furthermore, this study revealed negative significant relationships of IFN-γ secretion with regard to CD4+HLA/DR+ and CD8+HLA/DR+ as well as between IL-10 concentration and CD4+HLA/DR+ in trials without PHA stimulation. Our findings have confirmed a key role for tumor cells in determining the function of T cells involved in the immunological processes and impact of neoplastic cells on modulating the activity of T CD4+ and CD8+ lymphocytes in laryngeal carcinoma. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 579-592) [ABSTRACT FROM AUTHOR]

One of the most important challenges in contemporary oncology is to find objective biomarkers of tumor aggressiveness, which help to identify more invasive phenotypes of the carcinoma. The purpose of this study was to investigate the relationships between the early and the late activation markers expression on T CD4+ and CD8+ cells subpopulations and certain clinicopathological characteristics of the neoplastic infiltration in order to determine their role as biomarkers for tumor behavior in squamous cell laryngeal carcinoma. Analysis of the early (CD69+, CD71+) and the late activation antigens (CD25+high, CD26+, HLA/DR+) expression on T CD4+ and CD8+lymphocytes by cytofluorymetry in 55 patients treated for squamous cell laryngeal carcinoma was performed. Clinicomorphological analysis on the basis of TNM criteria and tumor front grading, which included tumor-related features and adjacent stroma-related characteristics of the peripheral edge of infiltration was carried out. The relationships between the activation markers expression and parameters of tumor aggressiveness were investigated. Our work revealed statistically significant differences in the expression of the studied activation markers on T cells with regard to certain clinicomorphological fetaures. The expressions of CD69+ and CD71+ antigens on T CD3+CD4+ and CD3+CD8+ cells as well as CD4+HLA/DR+ markers were higher for pT3 and pT4 tumors, in comparison with pT2 carcinomas. Moreover, tumors with the smallest number of TFG points were characterized by significantly lower values of the average expression of CD3+CD69+ and CD3+CD71+ as well as CD4+HLA/DR+ markers on T lymphocytes. In addition, more aggressive and deeply infiltrating laryngeal carcinomas were most often characterized by significantly higher values of the average expression of CD69+ and CD71+ antigens on CD8+ as well as HLA/DR+ markers on CD4+. Our study confirmed the implication of the early and the late activation antigens expression on CD4+ and CD8+ T lymphocytes in clinicomorphological parameters of the tumor, especially TFG total score and depth of invasion, and their importance as indicators of the invasive phenotype of laryngeal carcinoma. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 593-603) [ABSTRACT FROM AUTHOR]

Suppressor of cytokine signaling 1 (SOCS1) is the key regulator of cytokine-mediated innate and adaptive immunity. One of the molecular mechanisms of SOCS1 is connected with inhibition of TLR4-NFκB pathway. The relationships among these molecules in laryngeal carcinoma are not exactly known. In this preliminary study we focused on their special activity and role in regulation of development and progression of laryngeal carcinoma. To investigate NFκB (p65 subunit) nuclear and cytoplasmic expression in 45 tumor samples of advanced laryngeal carcinoma IHC staining was performed. To determine the mRNA expression levels of TLR4, IRAK1, TRAF6 and SOCS1 in isolated neoplasm cells and non-cancerous adjacent mucosa epithelial cells RT-PCR was used. The invasiveness of laryngeal carcinomas was evaluated according to tumor front grading, TFG, which included tumor-related features (cytoplasmic differentiation, nuclear polymorphism, number of mitoses) and adjacent stroma-related characteristics of the peripheral edge of tumor infiltration (mode of infiltration, depth of invasion and plasmalymphocytic infiltration). The relationships between pT, pN status, the histological G grade, certain clinicopathological characteristics as well as postoperative observation time and the mRNA expression of the molecules mentioned earlier were investigated. Significant differences of TLR4-NFκB pathway molecules and SOCS1 mRNA expression in laryngeal tumor cells and normal adjacent mucosa cells as well as significant interconnections of TLR4, SOCS1 and NFκB(p65) in isolated tumor cells were obtained. This preliminary study demonstrated that the expression of SOCS1 and TLR4-NFκB pathway molecules had a strong association with the aggressiveness of laryngeal carcinoma. Positive relationships of TRAF6 in tumor margin cells with the histological grade and the mode of tumor invasion as well as the TFG total score were highlighted. Significant positive correlations were found between the TLR4 in tumor central cells and the TFG total score. Negative relationships of SOCS1 in tumor central cells with the histological grade were also noted. Significant positive correlations were found between the cytoplasmic NFκB(p65) and the mode of invasion as well as TFG total score. Our findings confirmed the importance of SOCS1 and TLR4-NFκB pathway molecules as potential biomarkers for assessment of the aggressive tumor phenotype in laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

In this study we present results of investigations of progesterone and estrogen receptors in most frequent, WHO grade I histological types of meningiomas (meningothelial, fibrous, and transitional) and in atypical - WHO grade II variant of these tumors. Samples from 64 tumors were examined. The cohort consisted of 46 WHO grade I (21 transitional, 13 fibrous and 12 meningothelial histologic variants) and of 18 atypical meningiomas. Apart from immunohistochemical examination of progesterone and estrogen receptors, MIB 1 labeling index was estimated. Positive immunoreaction for progesterone receptors was found in 100% meningothelial, 95% transitional, 46% fibrous and 78% atypical variant of meningiomas. Intensity of immunoreaction was stronger in grade I than in grade II tumors. Immunoexpression of estrogen receptors was found in 48% of the investigated meningiomas. No correlation was stated between WHO grade I and grade II tumors, and between meningothelial, transitional and fibrous variants of the neoplasms. [ABSTRACT FROM AUTHOR]

Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. [ABSTRACT FROM AUTHOR]

Topoisomerase IIβ binding protein 1 (TopBP1), a multiple-BRCT-domain, protein plays crucial roles in chromosome replication, DNA damage repair, apoptosis, and cell cycle checkpoint signalling. The aim of this study was to identify five SNPs at loci potentially located in the 3'UTR region of the TopBP1 gene (rs185903567, rs116645643, rs115160714, rs116195487, rs112843513), their relationship with the risk of squamous cell laryngeal cancer (SCLC), tumor invasiveness, and prognosis. Genotyping was performed in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Allele-specific TopBP1 mRNA and protein expressions were determined by using real-time PCR and Western blotting techniques, respectively. LOH in BRCA1/BRCA2 was determined by using microsatellite markers. Compared to homozygous common allele carriers, heterozygosity for the T variant was associated with increased risk of SCLC (adjusted odds ratio [OR] = 9.83, 95 % confidence interval [CI]: 3.12-22.16, p dominant < 0.0001). The presence of risk allele at rs115160714 TopBP1 determined a higher incidence of nodal metastases (OR = 7.98, 95 % CI: 3.94-16.00, p = 0.001) and higher tumor grade (OR = 6.48, 95 % CI: 0.86-48.01, p = 0.03). The heterozygotes displayed diffuse tumor growth with no distinct borderline (OR = 3.10, 95 % Cl: 0.92-10.62, p = 0.049) and higher depth of invasion (OR = 2.66, 95 % Cl: 0.78-9.03, p = 0.04). Relationships were also identified between TopBP1 mRNA/protein expression and overall survival (p < 0.0001). The incidence of LOH in BRCA1/BRCA2 was significantly related to higher tumor grade and TFG (p < 0.05). The results of this study suggest that rs115160714 TopBP1 may be a genetic marker of etiology and progression in laryngeal cancer.

Aim of the Study: Expression of EP2 protein, the prostaglandin E2 (PGE2) receptor, produced by tumour microenvironment inflammatory cells as well as tumour cells, may promote cellular proliferation and growth in an autocrine and paracrine fashion. The phenomenon involving these proteins is regulated by interleukin 1β (IL-1β). Many researchers indicate a connection of EP2 and IL-1β in various types of neoplasms with higher tumour progression and poor prognosis. The aim of this study was to analyse the EP2 expression within laryngeal carcinoma tissue and IL-1β levels in peripheral blood mononuclear cell supernatants and to find relationships between clinicomorphological features., Material and Methods: A group of 50 patients with verified squamous cell laryngeal carcinoma was analysed in this study. The pathological evaluation included pTNM depth of invasion according to tumour front grading criteria. Immunohistochemical analysis for membranous staining of EP2 in tumour tissues was used. The IL-1β expression was determined by enzyme-linked immunosorbent assay (ELISA)., Results: Increased EP2 expression in carcinoma cells was confirmed for more advanced tumours (pT3-pT4 vs. pT1-pT2, p < 0.0001 and pN1-3 vs. pN0, p = 0.02). Tumours with the highest aggressiveness identified by deeper invasion of submucosa or cartilage were characterised by the highest expression of EP2 (p < 0.0001). In laryngeal carcinomas characterised by a lower differentiation the highest EP2 expression in tumour cells was noted (p = 0.009). A positive relationship between IL-1β expression and the presence of lymph node metastases was also confirmed (p = 0.04)., Conclusions: The study indicates the potential effect of EP2 receptor and IL-1β on tumour progression in laryngeal carcinoma.

Introduction: Despite extensive research in the field of molecular biology, immunology and histopathology, prognostically unambiguous morphological indicators of the invasiveness of tumor which allow the prediction of disease course in laryngeal cancer have not yet been identified. The aim of this study was to analyze gene and protein expression of HIF-1a and COX-2 in the tumor stroma and to find relationships between clinical and morphological features (pT, G, depth of tumor invasion, plasmalymphocytic infiltration) and certain markers in squamous cell laryngeal carcinoma., Material and Methods: We analyzed a group of 59 patients with verified squamous cell carcinoma of the larynx. The pathological evaluation was included pTNM classification criteria, depth of invasion according to tumor front grading and degree of morphological differentiation. Quantitative analysis of the amplified product in real time (real-time RT2-PCR) for estimation of mRNA HIF-1a and COX-2 expression in tumor cells were used. The level of HIF-1a and COX-2 protein expression by Western blot analysis was determined., Results: In studied group of laryngeal cancers significant differences in expression of certain molecules analyzed in tumor tissue and noncancerous epithelium of the larynx have been shown. Increased expression of HIF-1a and COX-2 at both mRNA and protein level was indicator of greater aggressiveness of the tumor, evaluated on the basis of clinical and morphological features in laryngeal squamous cell carcinomas. Tumors with the most invasive growth (pT4 stage, low-differentiated tumors G3, neoplastic infiltration with invasion of cartilage of the larynx) had the highest expression of HIF-1a and COX-2 at the mRNA and protein level., Conclusions: The study pointed out the direction for further research to find unambiguous indicators for estimation of tumor invasiveness and the possibility of practical use of HIF-1a and COX-2 mRNA and protein level assessment as important methods for determining the advancement of clinical and morphological changes in laryngeal cancer, thereby selecting an appropriate model of treatment., (Copyright © 2011 Polish Otolaryngology Society. Published by Elsevier Urban & Partner (Poland). All rights reserved.)

Introduction: The degree of activation of cells involved in cellular immune response against tumor antigens (cytotoxic lymphocytes Tc) as well as efficiency of the mechanisms which promote immunosuppression (Treg - regulatory cells CD4(+)CD25(+)Foxp3(+)) may determine the course of the neoplastic disease. The aim of this study was to assess the function of autologous peripheral blood mononuclear cells (PBMCs) involved in the immunological processes on the basis of expression of Foxp3 and RORgamma t molecules as well as analysis of the relationships with clinical and morphological features of the tumor (pT and pN stage, G feature, degree of invasiveness according to the TFG classification) in laryngeal carcinoma., Material and Methods: The analysis included a group of 59 patients with verified squamous cell carcinoma of the larynx. In the pathologic evaluation pTNM classification criteria, depth of invasion and degree of histological differentiation were used. Expression levels of mRNA for Foxp3 and RORgamma t in peripheral blood mononuclear cells by quantitative analysis of the amplified product in real time (real-time RT(2)-PCR) were evaluated. The level of Foxp3 and RORgamma t protein expression by Western blot analysis was determined., Results: In squamous cell carcinomas of the larynx, with the highest tumor aggressiveness the significantly highest level of mRNA and protein expression for Foxp3 molecule were observed. The severity of Foxp3 expression at both gene and protein level were positively linearly correlated with the degree of local extent of the tumor (pT3-4), depth of invasion (invasion of cartilage) and the degree of histological differentiation (low-differentiated tumors G3). In the study group of laryngeal cancers significantly lower level of RORgamma t expression in carcinomas with less invasive changes (pT1-2, high-differentiated tumors G1, carcinomas with microinvasion without evidence of invasion beyond the lamina propria) was also noted., Conclusions: The study results indicate the important role of immune cell activity as indicators of advancement of clinical and morphological changes in squamous cell carcinoma of the larynx., (Copyright © 2011 Polish Otolaryngology Society. Published by Elsevier Urban & Partner (Poland). All rights reserved.)

The role of interactions between tumor cells and autologous immunocompetent cells, the impact on the modulation of the activity of T CD4(+) and CD8(+) lymphocytes, as well as the influence on the regulation and determination of antitumor cellular immune response in patients with head and neck squamous cell carcinomas (HNSCC) is not completely clear. The aim of this study was to analyze early and late activation antigens expression on T cells subpopulations modified under the influence of the presence of cancer cells to investigate the regulatory mechanisms of the local cellular immune response in carcinoma of the larynx. Cytofluorymetric analysis of the early (CD69(+), CD71(+)) and late activation markers (CD25(+) (high), CD26(+), HLA/DR(+)) expression on T CD3(+)CD4(+) and CD3(+)CD8(+) cells subpopulations in mixed cellular cultures of freshly isolated tumor cells (MLTMC) and non-cancerous normal epithelial cells (MLNCC) with immunocompetent cells was performed in 55 cases of squamous cell laryngeal carcinoma. The whole peripheral blood concentrations of IL-10 and IFN-γ in 21 h and 72 h of experiments were also measured by ELISA. The relationships between the activation markers expression depending on the type of cells used in co-cultures, as well as the level of secreted cytokines, were investigated. Our work has revealed a statistically significant dependence of cytofluorymetric results on the presence of TMC or NCC in mixed cellular cultures. Increased expression of CD69(+), CD71(+) and CD25(+) (high), CD26(+), HLA/DR(+) antigens on T CD3(+)CD4(+) and CD3(+)CD8(+) cells was higher in MLTMC cultures, in comparison with MLNCC. We demonstrated negative significant relationships of IFN-γ and IL-10 secretion with regard to CD4(+)CD69(+), CD8(+)CD69(+), CD4(+)CD71(+), CD8(+)CD71(+) antigens expression in 21 h of experiments without mitogenic stimulation. Furthermore, this study revealed negative significant relationships of IFN-g secretion with regard to CD4(+)HLA/DR(+) and CD8(+)HLA/DR(+) as well as between IL-10 concentration and CD4(+)HLA/DR(+) in trials without PHA stimulation. Our findings have confirmed a key role for tumor cells in determining the function of T cells involved in the immunological processes and impact of neoplastic cells on modulating the activity of T CD4(+) and CD8(+) lymphocytes in laryngeal carcinoma.

One of the most important challenges in contemporary oncology is to find objective biomarkers of tumor aggressiveness, which help to identify more invasive phenotypes of the carcinoma. The purpose of this study was to investigate the relationships between the early and the late activation markers expression on T CD4(+) and CD8(+) cells subpopulations and certain clinicopathological characteristics of the neoplastic infiltration in order to determine their role as biomarkers for tumor behavior in squamous cell laryngeal carcinoma. Analysis of the early (CD69(+), CD71(+)) and the late activation antigens (CD25(+) (high), CD26(+), HLA/DR(+)) expression on T CD4+ and CD8(+) lymphocytes by cytofluorymetry in 55 patients treated for squamous cell laryngeal carcinoma was performed. Clinicomorphological analysis on the basis of TNM criteria and tumor front grading, which included tumor-related features and adjacent stroma-related characteristics of the peripheral edge of infiltration was carried out. The relationships between the activation markers expression and parameters of tumor aggressiveness were investigated. Our work revealed statistically significant differences in the expression of the studied activation markers on T cells with regard to certain clinicomorphological features. The expressions of CD69(+) and CD71(+) antigens on T CD3(+)CD4(+) and CD3(+)CD8(+) cells as well as CD4(+)HLA/DR(+) markers were higher for pT3 and pT4 tumors, in comparison with pT2 carcinomas. Moreover, tumors with the smallest number of TFG points were characterized by significantly lower values of the average expression of CD3(+)CD69(+) and CD3(+)CD71(+) as well as CD4(+)HLA/DR(+) markers on T lymphocytes. In addition, more aggressive and deeply infiltrating laryngeal carcinomas were most often characterized by significantly higher values of the average expression of CD69(+) and CD71(+) antigens on CD8(+) as well as HLA/DR(+) markers on CD4(+). Our study confirmed the implication of the early and the late activation antigens expression on CD4(+) and CD8(+) T lymphocytes in clinicomorphological parameters of the tumor, especially TFG total score and depth of invasion, and their importance as indicators of the invasive phenotype of laryngeal carcinoma.

Background: Epidermal growth factor receptor (EGFR) and proinflammatory cytokines have been implicated in the dysregulated cell growth and increased aggressiveness of human cancers. The purpose of this study was to analyze EGFR immunoexpression in neoplastic tissues and IL-6 and TNFalpha secretion by peripheral blood mononuclear cells (PBMCs) and to investigate their relationships with certain clinicopathological characteristics., Material/methods: Tumor expression of membranous and cytoplasmic EGFR was measured in 45 cases of laryngeal squamous cell carcinoma by IHC staining. IL-6 and TNFalpha concentrations in 21-h PBMC cultures were measured by ELISA. Relationships between EGFR and cytokine secretion and clinicopathological characteristics such as pT status, pN status, and TFG classification, which include the parameters of the most invasive zones of neoplastic tissue and histological grade, were analyzed., Results: The membranous EGFR index had a very strong association with pT stage, mode of invasion, and lymphocytic plasma infiltration of the tumor stroma. Relationships between the cytoplasmic EGFR index and nuclear polymorphism as well as TFG score for advanced carcinomas and histological grade in less invasive tumors were highlighted. The correlations of IL-6 and TNFalpha levels with TFG score, pT status, histological grade, and mode of tumor invasion were also significant., Conclusions: These findings confirmed the importance of EGFR immunoexpression rate as well as IL-6 and TNFalpha secretion by PBMCs as potential biomarkers for assessing the aggressive tumor phenotype in laryngeal carcinoma.