title: Reduced p16 expression correlates with lymphatic invasion in colorectal cancers.
abstract: OBJECTIVE
  P16, the tumor suppressor gene, plays a crucial role in the most important regulatory pathway involved in the G1/S transition, but its role in gastrointestinal neoplasia remains unclear.
  
  
  METHODS
  To evaluate the possible p16 role in the development of colonic neoplasms, the authors studied p16 immunohistochemical expression of 84 lesions of colorectal cancers, 6 lesions of hyperplastic polyps, 59 lesions of adenomas and 8 lesions of carcinoma in adenoma. Immunohistochemical staining was processed by streptavidin biotin technique. The degree of expression pattern was classified into four types: absent, scattered, or nested, diffuse. Also, the correlation between immunohistochemical expression pattern and clinicopathological features was evaluated.
  
  
  RESULTS
  Compared with normal colonic mucosa, in which virtually no p16 expression was observed, p16 was overexpressed in hyperplastic polyps (33%:2/6) adenomas (46%:27/59), carcinoma in adenoma (88%:7/8) and in adenocarcinomas (98%:82/84). In colorectal cancers, when divided into positive (diffuse or nested) and negative (absent or scattered) subgroups, the negative group showed a higher ratio of lymphatic infiltration (p = 0.04), a higher ratio of deeper invasion (p < 0.01) and a higher ratio showing histology of mucinous carcinoma or poorly differentiated adenocarcinoma (p < 0.01).
  
  
  CONCLUSIONS
  In colorectal cancers, a significant correlation of reduced p16 expression and lymphatic invasion was observed, which suggested and colorectal cancers with reduced p16 expression have more aggressive potential of lymphatic infiltration. Also a significant correlation between the overexpression of p16 and tumor progression was demonstrated.
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. tadat-sur@h.u-tokyo.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kazama
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hata
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Komuro
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D012007:Rectum / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16