Vahedi Laleh, Ghasemi Maryam, Yazdani Jamshid, Ranjbar Samaneh, Nouri Banafshe, Alizadeh Ahad, Afshar Parvaneh
Department of Pathology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Biological Statistics and Epidemiology, School of public Health, Mazandaran University of Medical Sciences, Sari, Iran.
Int J Hematol Oncol Stem Cell Res. 2018 Apr 1;12(2):103-110.
Breast cancer is one of the most common cancers among women in the world, especially in Iran. There are large numbers of molecular and genomic factors causing breast cancer as well as many markers associated with tumor invasion. Chemokines are small proteins that primarily regulate leukocyte trafficking in the homeostatic conditions and specific immune responses. Chemokine receptor 7 (CCR7) belongs a class A subtype 7-span transmembrane G-protein coupled receptor. CCR7 plays a role in the migration of tumor cells such as immune cells into lymphoid organs through binding to its only two ligands CCL19/CCL21. High expression of this marker has been observed in breast cancer. However, there have been limited and contradictory data in studies conducted on the relationship between the increasing expression of this marker with various clinical and pathological factors. This case-control practical study was carried out on total mastectomy samples from 70 patients with breast cancer and tumor-adjacent normal tissue using immunohistochemistry technique to assess the expression of CCR7 marker. The relationship among the marker expression with different clinical and pathological tumor factors such as age, tumor size, microscopic grade, neurovascular invasion, lymph node metastasis and tumor stage were evaluated in all patients. Since the both groups were matched for age, so McNemar test, Chi-square test and Fisher's exact test were used to compare the expression of CCR7 marker in the case and control groups. Conditional logistic regression was employed to compare the effects of other variables regarding the age harmonization. CCR7 expression was observed in 63 (91.4%) out of 70 studied patients and in tumor-adjacent normal tissue of 55 patients (78.6%), while the marker expression intensity in normal tissue was lower than tumoral tissue (P<0.032) There was a significant relationship among the expression of CCR7 marker with disease stage (P<0.001), grade (P<0.035), lymph node metastasis (P<0.003), perineural invasion (P<0.037) and vascular invasion (P<0.01), but no significant relationship was found among CCR7 expression with other tumor clinicopathologic parameters such as age (P>0.19) and tumor size (P>0.105). Increased expression of CCR7 has a significant relationship with disease stage, grade, lymph node metastasis and neurovascular invasion of breast cancer but has no relationship with age of patients and tumor size. Therefore, this biomarker can be utilized as a predictive factor for tumor metastasis and survival of patients.
乳腺癌是全球女性中最常见的癌症之一,在伊朗尤为如此。导致乳腺癌的分子和基因组因素众多,与肿瘤侵袭相关的标志物也很多。趋化因子是一类小蛋白质,主要在稳态条件下调节白细胞运输和特定免疫反应。趋化因子受体7(CCR7)属于A类7跨膜G蛋白偶联受体。CCR7通过与其仅有的两种配体CCL19/CCL21结合,在肿瘤细胞(如免疫细胞)向淋巴器官的迁移中发挥作用。在乳腺癌中已观察到该标志物的高表达。然而,关于该标志物表达增加与各种临床和病理因素之间关系的研究数据有限且相互矛盾。本病例对照实用性研究对70例乳腺癌患者的全乳切除样本及肿瘤邻近正常组织采用免疫组织化学技术,以评估CCR7标志物的表达。在所有患者中评估了该标志物表达与不同临床和病理肿瘤因素(如年龄、肿瘤大小、显微镜下分级、神经血管侵犯、淋巴结转移和肿瘤分期)之间的关系。由于两组年龄匹配,因此采用McNemar检验、卡方检验和Fisher精确检验来比较病例组和对照组中CCR7标志物的表达。采用条件逻辑回归来比较其他变量在年龄匹配方面的影响。在70例研究患者中的63例(91.4%)以及55例患者(78.6%)的肿瘤邻近正常组织中观察到CCR7表达,而正常组织中标志物表达强度低于肿瘤组织(P<0.032)。CCR7标志物的表达与疾病分期(P<0.001)、分级(P<0.035)、淋巴结转移(P<0.003)、神经周围侵犯(P<0.037)和血管侵犯(P<0.01)之间存在显著关系,但在CCR7表达与其他肿瘤临床病理参数(如年龄(P>0.19)和肿瘤大小(P>0.105))之间未发现显著关系。CCR7表达增加与乳腺癌的疾病分期、分级、淋巴结转移和神经血管侵犯显著相关,但与患者年龄和肿瘤大小无关。因此,这种生物标志物可作为肿瘤转移和患者生存的预测因素。