Transforming growth factor alpha (TGF-alpha) expression in dysplastic oral leukoplakia: modulation by 13-cis retinoic acid.
BACKGROUND
Surrogate endpoint biomarkers (SEBs) are detectable molecular, cellular, and tissue changes that take place during tumorigenesis and can be modulated by a chemoprevention agent.


METHODS
To identify candidate SEBs for invasive squamous cell carcinoma of the upper aerodigestive tract (SCC), we have studied the expression of transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFr) in sequential biopsy specimens of dysplastic oral leukoplakia and adjacent normal-appearing mucosa. Biopsies were taken from patients before, during, and after treatment with 13-cis retinoic acid, a vitamin A derivative. Immunohistochemistry was performed using the Biogenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system.


RESULTS
The pretreatment expression of TGF-alpha and EGFr in dysplastic oral leukoplakia was increased when compared with their expression in adjacent normal-appearing mucosa (p = 0.001 and p = 0.01, respectively). Eleven of 14 patients enrolled in the study (78.6%) completed 3 months of treatment with 13-cis retinoic acid (1. 0 mg/kg/day). TGF-alpha expression in dysplastic oral leukoplakia, but not in adjacent normal-appearing mucosa, decreased during treatment (p < 0.05).


CONCLUSIONS
TGF-alpha is a candidate SEB for future SCC chemoprevention trials.
Beenken
S W
SW
Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Sellers
M T
MT
Huang
P
P
Peters
G
G
Krontiras
H
H
Dixon
P
P
Stockard
C
C
Listinsky
C
C
Grizzle
W E
WE
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D018890:Chemoprevention; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007972:Leukoplakia, Oral / Q000188:drug therapy / Q000473:pathology*; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D010865:Pilot Projects; D016037:Single-Blind Method; D016211:Transforming Growth Factor alpha / Q000032:analysis* / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007641:Keratolytic Agents; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D015474:Isotretinoin