Saka Burcu, Ekinci Ozgur, Dursun Ayse, Akyurek Nalan
Department of Pathology Istanbul Medipol University, Bagcilar, Istanbul, Turkey.
Department of Pathology, Gazi University School of Medicine, Ankara, Turkey.
Pathol Res Pract. 2017 Jul;213(7):783-792. doi: 10.1016/j.prp.2017.04.001. Epub 2017 Apr 14.
To investigate the immunohistochemical expressions of HIF-1α, CA9 and CXCR4 in resected human CRC specimens in relation to clinicopathologic and prognostic variables.
A total of 186 patients (mean(SD) age: 56.7(12.6) years, 54.0% were males) with colorectal adenocarcinoma were included in this retrospective study. Resection specimens of the primary tumor were reviewed to confirm the diagnoses and the stage of the disease. Data on age, gender, tumor characteristics (localization, size, macroscopic growth pattern, histologic type, grade, angiolymphatic invasion, TNM stage), applied treatments and clinical outcome (overall survival, local recurrence and distant metastasis) were obtained from the hospital records. Immunohistochemical analysis of tissue specimens was performed to determine HIF-1α, CA9 and CXCR4 expressions.
Overall, 94.0% of cases showed HIF-1α immunoreactivity, 89% showed CXCR4 immunoreactivity, and 15.6% showed CA9 immunoreactivity, while weak expression of immunohistochemical markers was noted in 51.1%, 93.0% and 50.5% of cases, respectively. HIF-1α expression was higher among males than in females (median (min-max) final score of 6 (0-9) vs. 3 (0-9), p=0.013). CA9 expressed at higher levels in ulcerovegetative and depressed tumors than in polypoid ones [0(0-9) vs. 0(0-6), p=0.039]. CXCR4 expression was significantly higher in tumors <5cm than ≥5cm [6(0-9) vs. 3(0-9), p=0.028] and in grade 1-2 than grade 3 tumors [4(0-9) vs. 3(0-9), p=0.030]. No significant difference was noted in survival with respect to strength of HIF-1α, CA9 and CXCR4 immunoreactivity.
In conclusion, our findings revealed weak-to-moderate HIF-1α and CXCR4 immunoreactivity in majority of resection samples, and weak CA9 immunoreactivity in majority of CA9 positive cases. Other than gender (HIF-1α), macroscopic growth pattern (CA9) and tumor size and histologic grade (for CXCR4), none of the clinicopathologic and prognostic factors investigated were associated with expression of immunohistochemical markers and level of immunoreactivity had no impact on survival.
研究人结肠癌切除标本中缺氧诱导因子-1α（HIF-1α）、碳酸酐酶9（CA9）和CXC趋化因子受体4（CXCR4）的免疫组化表达与临床病理及预后变量的关系。
本回顾性研究纳入了186例结肠腺癌患者（平均（标准差）年龄：56.7（12.6）岁，54.0%为男性）。对原发性肿瘤的切除标本进行复查以确诊疾病并确定分期。从医院记录中获取年龄、性别、肿瘤特征（定位、大小、大体生长模式、组织学类型、分级、血管淋巴管浸润、TNM分期）、应用的治疗方法及临床结局（总生存期、局部复发和远处转移）等数据。对组织标本进行免疫组化分析以确定HIF-1α、CA9和CXCR4的表达。
总体而言，94.0%的病例显示HIF-1α免疫反应性，89%显示CXCR4免疫反应性，15.6%显示CA9免疫反应性，而免疫组化标记物的弱表达分别见于51.1%、93.0%和50.5%的病例。男性的HIF-1α表达高于女性（中位（最小值-最大值）最终评分为6（0-9）对3（0-9），p=0.013）。CA9在溃疡型和凹陷型肿瘤中的表达水平高于息肉型肿瘤[0（0-9）对0（0-6），p=0.039]。CXCR4在<5cm的肿瘤中的表达显著高于≥5cm的肿瘤[6（0-9）对3（0-9），p=0.028]，在1-2级肿瘤中的表达高于3级肿瘤[4（0-9）对3（0-9），p=0.030]。HIF-1α、CA9和CXCR4免疫反应性的强度与生存率无显著差异。
总之，我们的研究结果显示，大多数切除样本中HIF-1α和CXCR4的免疫反应性为弱至中度，大多数CA9阳性病例中CA9的免疫反应性为弱。除了性别（HIF-1α）、大体生长模式（CA9）以及肿瘤大小和组织学分级（CXCR4）外，所研究的临床病理和预后因素均与免疫组化标记物的表达无关，免疫反应性水平对生存率也无影响。
