title: Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C λ/ι, E-cadherin, β-catenin and basement membrane component.
abstract: Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat depressed-type tumors. The former of which shows a predominant lateral spreading growth rather than an invasive growth. The present study examined the morphological characteristics of LSTs, in comparison with polypoid- or flat depressed-type tumors, along with the expression of atypical protein kinase C (aPKC) λ/ι, a pivotal cell polarity regulator, and the hallmarks of cell polarity, as well as with type IV collagen, β-catenin and E-cadherin. In total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid-type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma (LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical examination was performed on aPKC λ/ι, type IV collagen, β-catenin and E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with expression of β-catenin and E-cadherin in the basolateral membrane and type IV collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of LST-CA showed aPKC λ/ι expression of 1+ (weak to normal intensity staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45% of the polypoid-type adenomas showed 2+ (moderate intensity staining in the cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were 3+ (strong intensity staining in the cytoplasm and nucleus). A statistically significant positive correlation was observed between the expression of aPKC λ/ι and β-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823; P<0.001). The LSTs showed a unique growth pattern, different from the expanding growth pattern presented by a polypoid tumor and invasive cancer. The growth characteristics of LST appear to be caused by adequate coexpression of β-catenin, type IV collagen and aPKC λ/ι.
authors.affiliation: Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Morioka
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Goto
authors.affiliation: Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawamata
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takagawa
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kunizaki
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Inayama
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 23600044, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
keywords: atypical protein kinase C λ/ι; laterally spreading tumor