Yoshihara Nagisa, Takagi Atsushi, Ueno Takashi, Ikeda Shigaku
Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
J Dermatol. 2014 Apr;41(4):311-5. doi: 10.1111/1346-8138.12439.
The expression of autophagy-related markers has occasionally been reported to correlate with the clinical stage of disease in patients with solid cancer, indicating autophagy activation. However, there have been no such reports for cutaneous squamous cell carcinoma. In this study, we investigated the expression levels of two autophagy-related markers, microtubule-associated protein IA/IB light chain 3 (LC3) and p62/sequestosome-1 (p62), in cutaneous squamous cell carcinoma specimens and assessed their correlation to clinicopathological factors in patients with this type of cancer. As a marker of the autophagosome, LC3 expression increases with autophagosome formation/accumulation, whereas p62 expression decreases due to selective degradation via autophagy. We performed immunostaining for LC3 and p62 in 50 cutaneous squamous cell carcinoma specimens obtained from patients treated by surgical resection, counted the number of cells that showed positive staining, and calculated the percentage of positive cells per low-power microscopic field. We next investigated the correlations between the expression levels of these markers and various clinicopathological factors. The results indicated that LC3 expression increased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.046). By contrast, the expression of p62 decreased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.001). These results suggest that autophagy becomes activated during disease progression in patients with cutaneous squamous cell carcinoma.
在实体癌患者中，自噬相关标志物的表达偶尔被报道与疾病的临床分期相关，提示自噬被激活。然而，对于皮肤鳞状细胞癌尚无此类报道。在本研究中，我们调查了两种自噬相关标志物，微管相关蛋白轻链3（LC3）和p62 / 聚集体蛋白1（p62）在皮肤鳞状细胞癌标本中的表达水平，并评估了它们与这类癌症患者临床病理因素的相关性。作为自噬体的标志物，LC3的表达随自噬体的形成/积累而增加，而p62的表达则因通过自噬的选择性降解而降低。我们对50例接受手术切除治疗患者的皮肤鳞状细胞癌标本进行了LC3和p62的免疫染色，计数显示阳性染色的细胞数量，并计算每个低倍显微镜视野下阳性细胞的百分比。接下来，我们研究了这些标志物的表达水平与各种临床病理因素之间的相关性。结果表明，LC3的表达随着临床分期的进展（P < 0.001）和肿瘤直径的增加（P = 0.046）而显著增加。相比之下，p62的表达随着临床分期的进展（P < 0.001）和肿瘤直径的增加（P = 0.001）而显著降低。这些结果表明，在皮肤鳞状细胞癌患者的疾病进展过程中自噬被激活。
