title: Large granule-aggregating non-polypoid colorectal neoplasm: a clinically-important entity with unique cell loss and proliferation kinetics.
abstract: The large non-polypoid colorectal neoplasm with a granule-aggregating appearance shows characteristic features clinicopathologically. The aim of this study was to investigate the developmental mechanisms of this unique lesion. Among large non-polypoid tumours with a diameter of 10 mm or more, 26 granule-aggregating tumours (GATs) were evaluated while using 19 polypoid tumours (PTs) as controls. Apoptosis and proliferation indices in the superficial and deeper portions of lesions were assessed by immunohistochemical staining with anti-ss-DNA and Ki-67 antibodies, respectively. These indices were also analyzed for clinicopathological conditions to clarify the developmental manner of GATs. The apoptosis index (AI) of GATs was significantly higher than that of PTs (p = 0.0003). Especially in the deeper portion of the tumour, the AI value of GATs (4.54, SD: 1.86) was statistically more significant than that (0.34, SD: 0.48) of PTs (p<0.001). However, irrespective of dysplasia, a higher AI of GATs in the deeper portion was demonstrated in the early stage (10-19 mm in diameter), in contrast to that of PTs (P = 0.0001). The Ki-67 labeling index as proliferation index (PI) of the deeper portion of GATs was 22.4 (SD: 7.8), which was significantly lower than that (33.4, SD: 11.7) of PTs (p = 0.0016). No significant differences in the superficial and the whole tumours were obtained comparing GATs and PTs. PI values of GATs increased with their size (p = 0.0034). The current investigation clearly indicates that colorectal adenomas/tumours with granule-aggregating appearance have a higher apoptosis index in the deeper portion. This was demonstrated from an early stage of growth. These characteristic cell loss and cell proliferation kinetics give this tumour unique clinical features, that is, a laterally spreading manner or infrequent invasion even after malignant transformation. Therefore, the importance of recognizing non-polypoid colorectal neoplasms with a granular feature as a new disease concept is emphasized.
authors.affiliation: Department of Research Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan. byoin@city.fujiyoshida.lg.jp
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: U
authors.initials: U
authors.lastname: Iino
authors.forename: H
authors.initials: H
authors.lastname: Fujii
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000737:chemistry / Q000473:pathology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000737:chemistry / Q000473:pathology*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000473:pathology; D020895:Enterocytes / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen