Coexpression of Ets-1 and p53 in oral carcinomas is associated with P-glycoprotein expression and poor prognosis.
OBJECTIVE
To determine the association between the expression of P-gp with Ets-1 and p53 proteins in oral squamous cell carcinomas (SCCs).


METHODS
Immunohistochemical analysis of Ets-1, P-glycoprotein (P-gp), and p53 proteins was carried out in 40 formalin-fixed, paraffin-embedded tissue sections from oral SCCs using specific antibodies for these proteins.


RESULTS
Expression of Ets-1 protein was observed in 27/40 (68%) cases, P-gp was overexpressed in 27/40 (68%) cases, and p53 accumulation was observed in 26/40 (65%) cases. Twenty-two of 27 (82%) SCCs showed concomitant overexpression of Ets-1 and P-gp underpinning an association between the expression of these two proteins ( P=0.007). Twenty-one of 27 (78%) Ets-1 overexpressing oral SCCs showed accumulation of p53 protein ( P=0.015). Nineteen of the 27 (70%) P-gp expressing tumours showed p53 accumulation. Concomitant Ets-1 and P-gp overexpression was significantly associated with poor prognosis ( P=0.002). In multivariate analysis using Cox's proportional hazards model, P-glycoprotein emerged as the most significant adverse predictor of disease-free survival (HR=6.2, P=0.003). The hallmark of the study was the significant association between the expression of Ets-1, P-gp, and p53 proteins in oral SCCs and their association with poor prognosis. Oral cancer patients showing concomitant expression of Ets-1, P-gp, and p53 proteins had shorter disease-free survival (median time of no recurrence=18 months) and worst prognosis ( P=0.001) as compared to the cases overexpressing any of these proteins.


CONCLUSIONS
Concomitant expression of Ets-1, P-gp, and p53 proteins adversely affects the clinical outcome in oral SCCs.
Soni
S
S
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Pande
P
P
Shukla
N K
NK
Ralhan
R
R
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009061:Mouth Mucosa; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D050783:Proto-Oncogene Proteins c-ets; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D018435:ATP Binding Cassette Transporter, Subfamily B; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases