Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma

Seema Nayak; Madhu Mati Goel; Annu Makker; Vikram Bhatia; Saumya Chandra; Sandeep Kumar; S P Agarwal

doi:10.1371/journal.pone.0138801

Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma

PLoS One. 2015 Oct 14;10(10):e0138801. doi: 10.1371/journal.pone.0138801. eCollection 2015.

Authors

Seema Nayak¹, Madhu Mati Goel¹, Annu Makker¹, Vikram Bhatia¹, Saumya Chandra¹, Sandeep Kumar², S P Agarwal³

Affiliations

¹ Department of Pathology, King George's Medical University, Lucknow, U.P. - 226003, India.
² All India Institute of Medical Sciences Bhopal, M.P. - 462026, India.
³ Department of Otorhinolaryngology, King George's Medical University Lucknow, U.P. - 226003, India.

Abstract

There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Carcinoma, Squamous Cell / diagnosis
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Case-Control Studies
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
Child
Female
Fibroblast Growth Factor 2 / genetics*
Fibroblast Growth Factor 2 / metabolism
Gene Expression Regulation, Neoplastic
Humans
Leukoplakia, Oral / diagnosis
Leukoplakia, Oral / genetics*
Leukoplakia, Oral / metabolism
Leukoplakia, Oral / pathology
Male
Middle Aged
Mouth Mucosa / metabolism
Mouth Mucosa / pathology
Mouth Neoplasms / diagnosis
Mouth Neoplasms / genetics*
Mouth Neoplasms / metabolism
Mouth Neoplasms / pathology
Oral Submucous Fibrosis / diagnosis
Oral Submucous Fibrosis / genetics*
Oral Submucous Fibrosis / metabolism
Oral Submucous Fibrosis / pathology
Receptor, Fibroblast Growth Factor, Type 2 / genetics*
Receptor, Fibroblast Growth Factor, Type 2 / metabolism
Receptor, Fibroblast Growth Factor, Type 3 / genetics*
Receptor, Fibroblast Growth Factor, Type 3 / metabolism
Signal Transduction

Substances

Biomarkers, Tumor
Fibroblast Growth Factor 2
FGFR2 protein, human
FGFR3 protein, human
Receptor, Fibroblast Growth Factor, Type 2
Receptor, Fibroblast Growth Factor, Type 3

Grants and funding

This work was supported by Indian council of Medical Research, New Delhi, India-110029 (Grant No. 5/13/56/2008-NCDIII, www.icmr.nic.in); and Council of Science and Technology (Uttar Pradesh), India (Grant No. CST/SERPD/D-1888(ii), www.cstup.gov.in). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.