p53 immunoexpression: an aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk?
BACKGROUND
Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Lugol chromoendoscopy (LC) has being shown a useful tool in the management of patients at high risk for SCCE. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may aid in early diagnosis. This study was carried out to investigate the p53 immunoexpression in esophageal mucosa of smokers and alcohol consumers and study its relationship with different degrees of histological findings and the role of LC to detect areas that express p53.


METHODS
Group 1: One hundred and eighty-two asymptomatic subjects at high risk for SCCE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years). Group 2: Twenty healthy volunteers who neither smoked nor consumed alcohol. Both groups underwent upper GI endoscopy plus LC, with biopsies of the esophageal mucosa. Expression of p53 protein was compared to histological findings.


RESULTS
Group 1: There was 25/182 (14%) Lugol's unstained areas. p53 protein was expressed in a stepwise fashion according to the severity of the histological findings: normal mucosa (12/103 or 12%), mild esophagitis (6/43 or 14%), moderate esophagitis (4/18 or 22%), severe esophagitis (1/3 or 33%), low-grade dysplasia (4/11 or 36%), high-grade dysplasia (2/2 or 100%) and squamous cell carcinoma (2/2 or 100%) (p=0.001). Nine in 25 (36%) patients with Lugol's unstained areas and 22/157 (14%) with normal appearing Lugol's stained mucosa expressed p53. Group 2: There was no Lugol unstained areas. The histological analysis and immunohistochemistry for p53 were normal with the exception of two patients that presented mild esophagitis and expressed p53. Unstained areas were 3.5 times (95% CI: 1.2-9.6) more likely to express p53 then stained ones. Alcoholics/smokers were 1.9 (95% CI: 0.4-8) times more likely to express p53 than non-alcoholics/non smokers.


CONCLUSIONS
In this study, we find an association between histological alterations, p53 expression and Lugol's unstained areas. It may point to a higher risk for SCCE. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized sub-group of individuals that may benefit from surveillance or intervention.
Fagundes
Renato B
RB
Gastroenterology Service, Medicine School of the Federal University of Santa Maria, Brazil. rfagundes@pro.viars.com.br
Melo
Carlos R
CR
Pütten
Antonio C K
AC
Moreira
Luis F
LF
de Barros
Sérgio G S
SG
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004396:Coloring Agents; D004938:Esophageal Neoplasms / Q000235:genetics*; D004941:Esophagitis / Q000150:complications / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D007454:Iodides; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics*
D004396:Coloring Agents; D007454:Iodides; D016159:Tumor Suppressor Protein p53; C010389:Lugol's solution