Prognostic value of TP53 transcriptional activity on p21 and bax in patients with esophageal squamous cell carcinomas treated by definitive chemoradiotherapy.
OBJECTIVE
The aim of this study was to evaluate biologic factors on survival and clinical response after definitive concomitant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).


METHODS
TP53 protein hyperexpression (immunochemistry [IHC]) and functional assay (FA) of TP53, measuring the ability of TP53 to transactivate p21 and bax reporter systems, were performed in patients with ESCC treated by CRT. The impact of parameters studied on survival and clinical response to CRT was assessed.


RESULTS
Thirty-eight patients with ESCC were included. TP53 alterations were detected in 84.2% of cases with FA. All TP53 mutations abolished the transactivation of p21 and bax reporter systems. After CRT, complete response rate was 55.3%. The median survival of the population was 17.5 months. Serum albumin (p = 0.002), weight loss <10% (p = 0.005), and response to treatment (p < 0.001) were significantly linked with survival. TP53 alteration in FA was not significantly predictive of response to CRT (p = 0.132) nor survival (p = 0.154).


CONCLUSIONS
Our results suggest that wild-type TP53 in ESCC could be associated with good response to definitive CRT. However, the small rate of ESCC with wild-type TP53 suggests that systematic determination of TP53 status is not appropriate for the management of the ESCC population.
Michel
Pierre
P
Department of Gastroenterology, Centre Henri Becquerel, Rouen University Hospital, Rouen, France. pierre.michel@chu-rouen.fr
Magois
Karine
K
Robert
Valerie
V
Chiron
Anne
A
Lepessot
Florence
F
Bodenant
Corinne
C
Roque
Isabelle
I
Seng
Sok K
SK
Frebourg
Thierry
T
Paillot
Bernard
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D016001:Confidence Intervals; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011003:Ploidies; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015996:Survival Rate; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D002945:Cisplatin; D005472:Fluorouracil