title: Cell cycle kinetic analysis of colorectal neoplasms using a new automated immunohistochemistry-based cell cycle detection method.
abstract: We have recently developed a new method called the immunohistochemistry-based cell cycle detection (iCCD), which allows the determination of cell cycle phases on a cell-by-cell basis. This automated procedure can be performed on tissue sections and involves triple immunostaining for geminin, cdt1, and γ H2A.X, which are nuclear proteins expressed sequentially, with a few overlaps, during the cell cycle. In the current study, we applied this technique to resected specimens of colorectal neoplasm to determine the usefulness of iCCD for the pathological examination of colorectal cancers. We examined 141 cases of colorectal cancers. Normal mucosa and adenomas were analyzed as controls. In nonneoplastic mucosa, we observed a pattern of distribution of the cells positive for these cell cycle markers. Adenomas showed a slight distortion in this pattern, the geminin-positive cells, indicative of S/G2/M phase, were localized in the upper one-third region of the crypts. In neoplastic mucosa, the marker expression pattern was disorganized. Compared with normal mucosa, colorectal neoplasms showed an increased proportion of geminin-positive cells and decreased percentages of cdt1-positive cells (G1 phase). However, we did not find significant difference in the expression pattern between adenomas and carcinomas. Cellular proportions were correlated with clinicopathological parameters such as microscopic vascular invasion and pT stages. In cases of preoperative adjuvant therapy, the proportion of geminin-positive cells decreased, whereas that of γ H2A.X-positive cells (indicative of apoptosis/degeneration) increased significantly. We believe that this novel method can be applied to clinical samples to evaluate cell cycle kinetics and the effects of preoperative adjuvant therapy in colorectal cancers.
authors: From the Division of Gastrointestinal Surgery (AT, YK), Department of Surgery, Kobe University Graduate School of Medicine; Department of Diagnostic Pathology (AT, TI, EY, NI); and Kobe Advanced Tissue Staining Center (TI, EY, NI), Kobe University Hospital, Kobe, Japan.
authors: Ayako
authors: A
authors: Tomono
authors: Tomoo
authors: T
authors: Itoh
authors: Emmy
authors: E
authors: Yanagita
authors: Naoko
authors: N
authors: Imagawa
authors: Yoshihiro
authors: Y
authors: Kakeji
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000236:Adenoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005260:Female; D064248:Geminin / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D020360:Neoadjuvant Therapy; D013194:Staining and Labeling
chemical_list: C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D064248:Geminin; C468783:H2AX protein, human; D006657:Histones
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