title: Clinico-Pathological Correlation of β-Catenin and Telomere Dysfunction in Head and Neck Squamous Cell Carcinoma Patients.
abstract: BACKGROUND
  Tumorigenesis is a complex process of accumulated alteration in function of multiple genes and pathways. Wnt signalling pathway is involved in various differentiation events during embryonic development and is conserved in various species.
  
  
  OBJECTIVE
  A multicentre collaborative initiative is undertaken to study the occurrence, prognosis and molecular mechanism of HNSCC (Head and Neck Squamous Cell Carcinoma) which is highly prevalent in eastern parts of India. From a large cohort of HNSCC tissue repository, 67 cases were selected for multi-parametric investigation.
  
  
  RESULTS
  67 cases showed stable β-catenin expression. We have seen correlation, if any, of the transcription factor - β-catenin, telomere maintenance and shelterin complex proteins - TRF2, Rap1 and hTert with respect to tumor differentiation and telomere dysfunction. Immunohistochemistry of β-catenin protein showed stable and high expression in tumor when compared to stroma. MDSCC (Moderately Differentiated Squamous cell carcinoma) cases expressed nuclear expression of β-catenin in invasive fronts and showed increased genomic instability. Higher frequency of Anaphase bridges was observed ranging from <3% in normal cut margin to 13% in WDSCC (Well differentiated squamous cell carcinoma) and 18% in MDSCC (Moderately differentiated Squamous cell carcinoma). There was significant decrease in telomere length in MDSCC (<4) when compared to the normal cut margin samples (<7). Quantitative Real Time-PCR confirmed a significant correlationship between stable β-catenin expression and poor clinical and pathological outcome.
  
  
  CONCLUSIONS
  The Stabilisation and accumulation of β-catenin was significant and correlated well with de-differentiation process as well as prognosis and therapy outcome of the patients in the cohort. Expression status of molecular markers such as β-catenin, hTert, TRF2 and RAP1 correlate significantly with the process of tumorigenesis and prognosis and may play a role in therapeutic management of Head and neck patients.
authors: 1. Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha-751024, India.
authors: Swatishree
authors: S
authors: Padhi
authors: 1. Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha-751024, India.
authors: Arka
authors: A
authors: Saha
authors: 2. Department of Surgical Oncology, Kalinga Institute of Medical sciences, Bhubaneswar, Odisha-751024, India. ; 5. Department of Surgical Oncology, Apollo Hospitals, Bhubaneswar, Odisha-751004, India.
authors: Madhabananda
authors: M
authors: Kar
authors: 1. Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha-751024, India.
authors: Chinmoy
authors: C
authors: Ghosh
authors: 3. Department of Pathology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, odisha-751024, India.
authors: Amit
authors: A
authors: Adhya
authors: 4. Department of Pathology, Apollo Hospitals, Bhubaneswar, Odisha-751004, India.
authors: Manas
authors: M
authors: Baisakh
authors: 4. Department of Pathology, Apollo Hospitals, Bhubaneswar, Odisha-751004, India.
authors: Nachiketa
authors: N
authors: Mohapatra
authors: 6. Genome Stability Laboratory, Yong Loo Lin School of Medicine, Department of Physiology, National University of Singapore, Singapore 117597.
authors: Shriram
authors: S
authors: Venkatesan
authors: 6. Genome Stability Laboratory, Yong Loo Lin School of Medicine, Department of Physiology, National University of Singapore, Singapore 117597.
authors: Manoor Prakash
authors: MP
authors: Hande
authors: 1. Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha-751024, India.
authors: Birendranath
authors: B
authors: Banerjee
keywords: Dedifferentiation; Genomic instability; HNSCC; MDSCC; WDSCC.; Wnt/β-catenin
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