title: Analysis of the anatomic subsites, gender and age in unresectable advanced colorectal carcinomas in Tochigi, Japan suggests a shift in location towards the right side colon in elderly patients treated with cetuximab.
abstract: Colorectal cancer is a frequently occurring cancer whose incidence has shown a marked increase in recent years. Additionally, an increase in right side colon in elderly patients has been identified. Therefore, a clinicopathological study was conducted in 49 patients with unresectable advanced colorectal carcinomas to elucidate the association of clinicopathological characteristics andK-rasmutation. Of the 49 patients included in this study, 24 were aged <60 years with a male/female (M/F) ratio of 16/8 and 25 patients were aged ≥60 years with a M/F ratio of 16/9. Of the patients aged ≥65 years, 15 patients were enrolled as controls and the M/F ratio was 9/6. Results revealed that with regard to the subsite of cancer, unresectable advanced colorectal carcinomas developed in the right-sided colon in 13 patients, left-sided colon in 19 patients and rectum in 17 patients. Right-sided colon carcinomas were commonly identified in the elderly patients aged ≥65 years, with a marked tendency in the female patients (P=0.024). Immunostaining was performed for the epidermal growth factor receptor (EGFR) antibody in 40 patients to determine whether theK-rasgene would yield positive results. The mutantK-rasgene was identified in 8 patients (20%) and the frequency was lower compared with that of the normal colorectal carcinomas. Anti-EGFR antibody (cetuximab) is considered to be a molecularly targeted agent for unresectable advanced colorectal carcinomas. The increase in incidence of right-sided colon carcinomas as well as the increase in the number of patients presenting with colorectal carcinomas means this issue should be addressed. Sessile serrated adenoma/polyp (SSA/P) withb-rafmutation and CIMP (CpG island methylator phenotype) abnormality as a precursor lesion of right-sided colon carcinoma is common and since cetuximab refractory wild-typeK-ras/mutantb-rafcolorectal carcinoma may increase in elderly patients and patients with right-sided colon carcinoma, a simultaneous examination for theK-rasandb-rafgene abnormalities for the treatment of colorectal cancer using anti-EGFR antibody (cetuximab) is crucial. In addition, the multidisciplinary assessments regarding the effect of such treatments is likely to be determined based on cumulative results, such as the duration of patient survival.
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ichikawa
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Takashi
authors.initials: T
authors.lastname: Maruoka
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293; ; First Department of Surgery, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: First Department of Surgery, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shida
authors.affiliation: First Department of Surgery, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Second Department of Surgery, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagata
authors.affiliation: Second Department of Surgery, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8603;
authors.forename: Naohiko
authors.initials: N
authors.lastname: Akimoto
authors.affiliation: Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8603;
authors.forename: Chouitsu
authors.initials: C
authors.lastname: Sakamoto
authors.affiliation: Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Toyama 930-0194;
authors.forename: Johji
authors.initials: J
authors.lastname: Imura
authors.affiliation: Department of Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498;
authors.forename: Munefumi
authors.initials: M
authors.lastname: Arita
authors.affiliation: Department of Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498;
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293; ; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University, Omori Medical Center, Ota-ku, Tokyo 143-8541, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University, Omori Medical Center, Ota-ku, Tokyo 143-8541, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Shimotsuga-Gun, Tochigi 321-0293;
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimori
keywords: K-ras gene; b-raf gene; cetuximab; epidermal growth factor receptor downstream pathway; refractory to anti-epidermal growth factor receptor; right side colon; unresectable advanced colorectal carcinomas