Starska Katarzyna, Forma Ewa, Lewy-Trenda Iwona, Stasikowska Olga, Bryś Magdalena, Krajewska Wanda M, Łukomski Marek
Department of Laryngological Oncology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland.
Folia Histochem Cytobiol. 2009 Jan;47(3):401-10. doi: 10.2478/v10042-009-0075-2.
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-NFkappaB 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 NFkappaB (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-NFkappaB pathway molecules and SOCS1 mRNA expression in laryngeal tumor cells and normal adjacent mucosa cells as well as significant interconnections of TLR4, SOCS1 and NFkappaB(p65) in isolated tumor cells were obtained. This preliminary study demonstrated that the expression of SOCS1 and TLR4-NFkappaB 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 NFkappaB(p65) and the mode of invasion as well as TFG total score. Our findings confirmed the importance of SOCS1 and TLR4-NFkappaB pathway molecules as potential biomarkers for assessment of the aggressive tumor phenotype in laryngeal carcinoma.
细胞因子信号转导抑制因子1（SOCS1）是细胞因子介导的先天性和适应性免疫的关键调节因子。SOCS1的分子机制之一与抑制TLR4-NFκB通路有关。喉癌中这些分子之间的关系尚不完全清楚。在这项初步研究中，我们重点关注它们在喉癌发生发展调控中的特殊活性和作用。为了研究45例晚期喉癌肿瘤样本中NFκB（p65亚基）的核内和胞质表达，进行了免疫组化染色。为了测定分离的肿瘤细胞和癌旁非癌黏膜上皮细胞中TLR4、IRAK1、TRAF6和SOCS1的mRNA表达水平，采用了逆转录-聚合酶链反应（RT-PCR）。根据肿瘤前沿分级（TFG）评估喉癌的侵袭性，TFG包括肿瘤相关特征（细胞质分化、核多态性、有丝分裂数）和肿瘤浸润周边边缘的相邻基质相关特征（浸润方式、浸润深度和浆淋巴细胞浸润）。研究了pT、pN状态、组织学G分级、某些临床病理特征以及术后观察时间与上述分子mRNA表达之间的关系。在喉肿瘤细胞和正常相邻黏膜细胞中，TLR4-NFκB通路分子和SOCS1 mRNA表达存在显著差异，并且在分离的肿瘤细胞中TLR4、SOCS1和NFκB（p65）之间存在显著的相互联系。这项初步研究表明，SOCS1和TLR4-NFκB通路分子的表达与喉癌的侵袭性密切相关。突出了肿瘤边缘细胞中TRAF6与组织学分级、肿瘤浸润方式以及TFG总分之间的正相关关系。发现肿瘤中心细胞中的TLR4与TFG总分之间存在显著正相关。还注意到肿瘤中心细胞中SOCS1与组织学分级之间的负相关关系。细胞质NFκB（p65）与浸润方式以及TFG总分之间存在显著正相关。我们的研究结果证实了SOCS1和TLR4-NFκB通路分子作为评估喉癌侵袭性肿瘤表型潜在生物标志物的重要性。
