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Abstract Objective: The prognostic importance of Tumor-Infiltrating Lymphocytes (TILs) in the tumor microenvironment of various cancers is increasingly recognized. In the present study, we aimed to investigate the prognostic value of CD3+, CD4+, CD8+, and CD45RO + TILs and their relation to histopathological features in larynx squamous cell carcinoma. Methods: Formalin-Fixed and Paraffin-Embedded (FFPE) samples from 63 primary larynx squamous cell carcinoma patients were immunostained for CD3, CD4, CD8, and CD45RO expression. Positive cells in micrographs from Invasive Margin (IM) and Tumor Center (CT) of tissue specimens counted by ImageJ software and their correlation with disease outcome were analyzed. Results: The expression level of TILs subpopulations was associated with clinicopathological markers as well as Overall Survival (OS) and Disease-Free Survival (DFS). In multivariate analysis, high frequency of CD45RO + cells in IM were confirmed as an independent prognostic marker for DFS (p = 0.007, HR = 4.968) and OS (p = 0.007, HR = 4.957). Similar findings were observed in the multivariate analysis of the combined frequency of CD45RO+cells in IM and CT. Conclusion: TILs are associated with patients clinicopathological features. Also, our findings indicate that CD45RO + TILs are a valuable marker for risk prediction in larynx SCC and could predict patients' outcomes.
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Context: Through the expression of different immunomodulatory molecules, mesenchymal stem cells (MSCs) play a significant role in the regulation of immune responses against tumor cells. Herein, the expression of major histocompatibility complex class I polypeptide-related sequence B (MIC B) as an immunomodulatory molecule was investigated on adipose-derived stem cells (ASCs) isolated from breast cancer patients (Stage II and III) and healthy individuals. Materials and Methods: ASCs were isolated enzymatically, and the expression of MIC B was measured using quantitative real-time polymerase chain reaction method before and after treatment with interferon γ (IFN-γ). The concentration of MIC B in the supernatant of ASCs and also sera of breast cancer and normal individuals were determined using ELISA method. Results: The expression of MIC B in normal ASCs and Stage II ASCs was higher than Stage III ASCs. However, after treatment with IFN-γ expression of MIC B in ASCs was conversely changed as cancer ASCs showed approximately 3.5 fold higher expression of MIC B compared to normal ASCs. The mRNA expression of MIC B in Stage III, Stage II, and normal ASCs showed 61 (P = 0.02), 13 (P = 0.01) and 3 (P > 0.05) fold higher expression after stimulation with IFN-γ compared to cells with no stimulation. Conclusion: Expression of MIC B and upregulation of this molecule in response to IFN-γ in cancer ASCs draw attention to the effective role of MSCs in the tumor microenvironment. However, more studies will be needed to further elucidate Natural-killer Group 2, member D (NKG2D) ligands-dependent immunomodulatory roles of ASCs in the tumor progression
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P53 tumoral suppressor gene harbors a functional polymorphism which codes either arginine (Arg) or proline (Pro) in the protein p53 of codon 72. Such polymorphism has been associated with the development or prognosis of head and neck squamous cell carcinoma (HNSCC). AIM: we assessed codon 72 p53 allelic frequencies and genotypes in HNSCC Iranian patients. STUDY DESIGN: Case Study. MATERIALS AND METHODS: a total of 132 HNSCC patients and 123 healthy controls were genotyped. DNA source was from mononuclear cells of the peripheral blood. DNA amplification was done by means of the allele-specific polymerase chain reaction. RESULTS: genotypes and allele distribution were not significantly different between patients and controls. Moreover, no statistically significant association was found between the 72 and p53 codon tumor location, gender or age at the time of diagnosis. However, the Pro/Pro genotype was significantly increase in stage IV patients (30.8 percent) when compared to stages I-III of the disease (11.1 percent) (p=0.03), and a significantly higher percentage of patients with the Pro allele had and a risk increase in stage IV disease (OR=2.2, 95 percent CI=1.2-4.2, p=0.01). CONCLUSION: data revealed that the p53 polymorphism do not impact the risk of HNSCC in Iranians, nonetheless, it can affect tumor progression to a higher tumor stage.
O gene supressor tumoral p53 abriga um polimorfismo funcional que codifica ou arginina (Arg) ou prolina (Pro) no códon 72 da proteína p53. Este polimorfismo tem sido considerado associado com o desenvolvimento e prognóstico do carcinoma espinocelular de cabeça e pescoço (CECP). OBJETIVO: Foram avaliados genótipo e freqüências alélicas do códon 72 do p53 em pacientes iranianos com CECP. TIPO DE ESTUDO: Estudo de Caso. MATERIAIS E MÉTODOS: Um total de 132 pacientes com CECP e 123 controles saudáveis foram genotipados. A fonte de DNA foi composta de células mononucleares do sangue periférico. A amplificação do DNA foi realizada através da reação em cadeia da polimerase específica para alelos. RESULTADOS: A distribuição dos alelos e genótipos não foi significativamente diferente entre os pacientes e controles. Além disso, nenhuma associação estatisticamente significativa foi encontrada entre o polimorfismo do códon 72 do p53 e localização, sexo ou idade no momento do diagnóstico. No entanto, o genótipo Pro/Pro estava significativamente aumentado em pacientes no estágio IV (30,8 por cento) quando comparado ao estágio I-III da doença (11,1 por cento) (p=0,03), e um número significativamente maior de doentes com o alelo Pro teve um aumento no risco de desenvolver doença no estágio IV (OR=2,2, IC= 95 por cento =1.2-4.2, p=0,01). CONCLUSÃO: Os dados revelaram que o polimorfismo do p53 não afeta o risco de CECP em iranianos; porém, pode afetar a progressão para um estágio superior tumor.