title: p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma.
abstract: OBJECTIVE
  p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC).
  
  
  METHODS
  Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed.
  
  
  RESULTS
  Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325).
  
  
  CONCLUSIONS
  Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.
authors.affiliation: Department of Medicine, Faculty of Medicine, King Abdulaziz University; Scientific Chair for Colorectal Cancer, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Ahwal
authors.affiliation: Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pathology, Faculty of Medicine, Minia University, Al-Minia, Egypt.
authors.forename: Wafaey
authors.initials: W
authors.lastname: Gomaa
authors.affiliation: Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Eman
authors.initials: E
authors.lastname: Emam
authors.affiliation: Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Yousif
authors.initials: Y
authors.lastname: Qari
authors.affiliation: Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Abdelbaset
authors.initials: A
authors.lastname: Buhmeida
authors.affiliation: Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Salman
authors.initials: S
authors.lastname: Radwi
authors.affiliation: Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Basim
authors.initials: B
authors.lastname: Al-Maghrabi
authors.affiliation: Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Qahtani
authors.affiliation: Department of Pathology, Faculty of Medicine, King Abdulaziz University; Scientific Chair for Colorectal Cancer, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jaudah
authors.initials: J
authors.lastname: Al-Maghrabi
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D009154:Mutation; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D046888:Tissue Array Analysis / Q000379:methods*; D015854:Up-Regulation
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)