title: Prognostic significance of cytoplasmic p27 in oral squamous cell carcinoma.
abstract: OBJECTIVE
  p27 is a cell cycle-dependent kinase inhibitor whose presence in nucleus is associated with good prognosis. Recent studies propose that when localized to cytoplasm, it functions as an oncogene and confers a poorer prognosis. This study aimed at analysing the subcellular localization of p27 and its prognostic significance in oral squamous cell carcinomas (OSCCs).
  
  
  METHODS
  Immunohistochemistry for p27 was carried out on 60 cases of OSCC (30 cases each of those with lymph node metastasis [LN+ve SCC] and without lymph node metastasis [LN-ve SCC]) and 30 normal mucosa. The relationship between p27 localization and prognosis was analysed statistically.
  
  
  RESULTS
  Nuclear immunopositivity was seen in 15%, 23%, 7% and 60%, while cytoplasmic immunopositivity was seen in 80%, 63%, 97% and 43% of all SCC, LN+ve OSCC, LN-ve SCC cases and normal mucosa, respectively. There was a significant inverse correlation between nuclear and cytoplasmic p27 immunopositivity (P = 0.001). Nodal status and tumour stage were the only two parameters that correlated with disease-free survival (DFS) in OSCC cases. However, in LN+ve SCC, a significantly shortened DFS was seen in cases with cytoplasmic p27 expression compared to those without (P = 0.02). Conversely, LN+ve SCC with nuclear p27 had longer DFS on comparison with those without (P = 0.04).
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first study to analyse cytoplasmic localization of p27 in OSCC and correlate with prognosis. Cytoplasmic localization is associated with poor prognosis in OSCC with lymph node metastasis allowing the consideration of cytoplasmic p27 in predicting prognosis and targeted therapeutic approaches.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Archana George
authors.initials: AG
authors.lastname: Vallonthaiel
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Dinda
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Aanchal
authors.initials: A
authors.lastname: Kakkar
authors.affiliation: Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Alok
authors.initials: A
authors.lastname: Thakar
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Satya N
authors.initials: SN
authors.lastname: Das
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: cell cycle-dependent kinase inhibitor; oral cancer; p27; squamous cell carcinoma