LAUSR

Colorectal cancer is one of the most frequent cancers with high morbidity and mortality rates. Despite current advances in surgical/multimodal therapies, the overall patient's survival of advanced colorectal cancer has been still low. Recent studies have proposed many novel biomarkers for the diagnosis and prognosis of colorectal cancer. Among them, immunohistochemically detectable tissue markers are useful for the pathologists. Useful prognostic tissue markers are limited in number, while several diagnostic tissue markers such as caudal type homeobox 2 (CDX2) have been established. The article authored by Koshino et al. describes the clinicopathological significance of phospho‐histone H3 (PHH3) expression in colorectal cancer. The authors focused on the immunohistochemical expression of four cellular proliferation markers: phospho‐histone H3 (PHH3), cyclin A (CCNA), geminin (GMNN), and marker of proliferation Ki‐67 (MKI67), and analyzed their clinicopathological significance using the 269 surgically resected colorectal cancers.4–6 They performed the immunostaining using an ordinary manufactured instrument (Ventana BenchMark XT; Roche Diagnostics, Basel, Switzerland), and detected clear immunohistochemical staining patterns of the four cellular proliferation markers. The authors demonstrated interesting results that patients with PHH3‐high (≥7 per high power field (HPF)) tumors showed a significantly longer 5‐year patient's survival than those with PHH3‐low (≤6 per HPF) (81.8% vs. 65.5%; P = 0.0047), while there was no significant association between CCNA, GMNN, or MKI67 expression and 5‐year patient's survival. PHH3 expression was significantly fewer in the tumor invasive area than the tumor surface, and significantly even fewer in the tumor invasive front than in the tumor invasive area. Furthermore, the multivariable Cox hazards regression analysis revealed PHH3‐high expression, well to moderately differentiated histology, and younger age (<70 years) as potential favorable factors, while lymph node metastasis, and peritoneal metastasis were shown as potential independent risk factors. It has been unclear why PHH3‐high expression was correlated with better clinical outcomes of the colorectal cancer patients. However, immunohistochemical PHH3 expression is easy to detect, and is thought to be one of the useful markers to predict the patient's survival of the advanced colorectal cancer.