title: Connecting cyto-nano-architectural attributes and epithelial molecular expression in oral submucous fibrosis progression to cancer.
abstract: OBJECTIVE
  Problems in pre-cancer diagnosis complicate cancer theragnosis as well as life expectancy. There is uncertainty regarding malignant transformation of oral submucous fibrosis (OSF), an oral pre-cancer with dysplastic (OSFWD) and non-dysplastic (OSFWT) subtypes. Understanding the structural, molecular and physical aspects of epithelial homeostasis may be useful.
  
  
  METHODS
  Histopathological grading of biopsy sections was performed using H&E staining. Alterations in epithelial surface architecture in different groups was evaluated using scanning electron microscopy (SEM). The expression of crucial epithelial genes (p63, CK-5/6, CK-10, E-cadherin and β-catenin) was studied by immunohistochemistry, Western blot and RT-PCR analysis.
  
  
  RESULTS
  SEM observations revealed that the surface epithelial ridge pattern became thick and dense, and pit pattern gradually decreased in OSFWD and oral squamous cell carcinoma (OSCC). p63, ΔNp63 and CK-5/6 were up-regulated in OSFWD and OSCC but down-regulated in OSFWT. CK-10 was down-regulated in OSFWD compared to OSFWT. Cytoplasmic expression of E-cadherin and β-catenin was elevated in dysplastic and cancerous conditions. Moreover, statistical correlation between SEM features (ridges and pits) and molecular attributes demonstrated a significant positive relationship between the ridge-to-pit ratio and p63 population density (r=0.85) and the ridge-to-pit ratio and CK-5/6 intensity (r=0.63).
  
  
  CONCLUSIONS
  Molecular changes related to epithelial progressive maturation and cellular proliferation are correlated with concomitant alteration of epithelial surface architecture which helps to predict the malignant potentiality of OSF.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.
authors.forename: Swarnendu
authors.initials: S
authors.lastname: Bag
authors.affiliation: Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal, India.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Pal
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.
authors.forename: Amrita
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: School of Bio Sciences and Technology & Centre for Biomaterials Science and Technology, Vellore Institute of Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: Raunak Kumar
authors.initials: RK
authors.lastname: Das
authors.affiliation: Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal, India.
authors.forename: Ranjan Rashmi
authors.initials: RR
authors.lastname: Paul
authors.affiliation: Department of Biochemistry, University of Calcutta, Kolkata, West Bengal, India.
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000648:ultrastructure; D018450:Disease Progression; D004847:Epithelial Cells / Q000737:chemistry / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D009062:Mouth Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000648:ultrastructure; D009914:Oral Submucous Fibrosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000648:ultrastructure; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: CANCER; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; ORAL PATHOLOGY