Alteration of p62/SQSTM1 Expression Is Uncommon in Gastrointestinal and Prostate Cancer Tissues

Sequestosome 1 (p62/SQSTM1) contains multiple domains that interact with key components in cellular processes and signaling, including autophagy, nuclear factor-kB (NF-kB) activation, and oxidative stress signaling. p62 behaves as an adaptor between autophagic machinery and ubiquitinated proteins and promotes autophagic degradation of ubiquitinated targets. Altered autophagy is accompanied by p62 accumulation and ubiquitinated proteins. p62 activates NF-kB signaling through binding with TRAF6 and RIP1. Additionally, by interacting with the Nrf2 binding site in Keap1, p62 competitively inhibits the Nrf2-Keap1 interaction, thereby activating the transcription of Nrf2 target genes that induces antioxidant responses. With respect to disease involvement, the p62-encoding gene is frequently mutated in Paget’s disease of bone. With respect to cancer, p62 is involved in many signaling pathways whose functions are important in cancer development. p62 acts either as a tumor suppressor (via the Wnt pathway) or a prooncogenic protein (via the NF-kB and mammalian target of rapamycin pathways). p62 is highly expressed in breast, lung, gastric, colon, esophageal, and hepatocellular carcinomas and is associated with poor cancer patient prognosis. In contrast, a recent study reported that p62 was downregulated in colon carcinomas. The aim of our study was to confirm whether p62 expression is altered in gastric and colorectal cancers and to address whether it is altered in other cancers. To determine whether alterations of p62 expression are present in other human cancers, we analyzed the expression of p62 in gastric cancer (GC), colorectal cancer (CRC), and prostate cancers (PCa) by immunohistochemistry using 11 tissue microarray (TMA) blocks. Cases of CRC (n=103) originated from the cecum (n=2), ascending colon (n=19), transverse colon (n=6), descending colon (n=4), sigmoid colon (n=28), and rectum (n=44). Cases of GC (n=100) consisted of 50 diffuse, 36 intesti-