Ibrahim Hanaa M, AbdElbary Abeer M, Mohamed Salem Y, Elwan Amira, Abdelhamid Mohamed I, Ibrahim Amr
Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Internal Medicine Department, Gastroenterology and Hepatology Unit, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
J Gastrointest Cancer. 2019 Sep;50(3):370-379. doi: 10.1007/s12029-018-0079-2.
Worldwide, gastric carcinoma (GC) is the 5th most common malignancies in both sexes representing 6.8% of the total fatalities and is the 3rd leading cause of cancer death representing 8.8% of total fatalities. In Egypt, GC considers the 12th leading cause of cancer death representing 2.2% of the total cancer mortality. A growing body of evidence supports that cancer stem cells (CSCs) are resistant to chemotherapy or radiation, and the cell adhesion molecule CD44 has been identified as a cell surface marker associated with cancer stem cell in several types of tumors including gastric cancer. CD44 regulates gastric stem cell proliferation by increasing cyclin D1 expression which represents an important regulatory protein in the cell cycle transition from G1 phase to S phase. This study aimed to investigate whether cyclin D1 and CD44 can be used as prognostic indicators in gastric cancer.
Forty formalin-fixed and paraffin-embedded gastric tissues, obtained from patients who underwent endoscopic resection or surgical resection, constituted the group of our study. The immunohistochemical expression of cyclin D1 and CD44 was examined and correlated with clinical-pathological parameters and outcome of the patients.
Overexpression of CD44 and cyclin D1 was noted (in of 55 and 50% respectively). Cyclin D1 and CD44 positive expressions in GC were positively correlated with tumor differentiation (p = 0.020, p = 0.004 respectively), TNM stage (p < 0.001 for both), poor survival (p < 0.001 for both), and with increased rate of recurrence (p = 0.020, p = 0.005 respectively).
CD44 and cyclin D1 were associated with poor prognosis in gastric cancer, and so, they comprise an attractive target for anticancer drug development.
在全球范围内,胃癌(GC)是男女中第五大常见恶性肿瘤,占总死亡人数的6.8%,是癌症死亡的第三大主要原因,占总死亡人数的8.8%。在埃及,胃癌是癌症死亡的第12大主要原因,占癌症总死亡率的2.2%。越来越多的证据支持癌症干细胞(CSCs)对化疗或放疗具有抗性,并且细胞粘附分子CD44已被确定为包括胃癌在内的几种肿瘤类型中与癌症干细胞相关的细胞表面标志物。CD44通过增加细胞周期蛋白D1的表达来调节胃干细胞增殖,细胞周期蛋白D1是细胞从G1期过渡到S期的细胞周期中的一种重要调节蛋白。本研究旨在探讨细胞周期蛋白D1和CD44是否可作为胃癌的预后指标。
从接受内镜切除或手术切除的患者中获取40份福尔马林固定石蜡包埋的胃组织,构成我们的研究组。检测细胞周期蛋白D1和CD44的免疫组化表达,并与患者的临床病理参数和预后相关联。
观察到CD44和细胞周期蛋白D1的过表达(分别为55%和50%)。胃癌中细胞周期蛋白D1和CD44的阳性表达与肿瘤分化呈正相关(分别为p = 0.020,p = 0.004),与TNM分期呈正相关(两者均为p < 0.001),与不良生存呈正相关(两者均为p < 0.001),并且与复发率增加呈正相关(分别为p = 0.020,p = 0.005)。
CD44和细胞周期蛋白D1与胃癌的不良预后相关,因此,它们是抗癌药物开发的有吸引力的靶点。