Immunohistochemical analysis of selected molecular markers in esophagus precancerous, adenocarcinoma and squamous cell carcinoma in Iranian subjects.
BACKGROUND
The molecular and cellular mechanisms linking chronic inflammation and gastrointestinal malignancy are not known with certainty.


OBJECTIVE
To investigate changes in potential causative factors during progression of esophagus cancer in a population living in high-risk area in Iran.


METHODS
Formalin-fixed, paraffin-embedded esophageal specimens (n=87) from patients with gastroesophageal reflux disease (GERD), Barrett's metaplasia, adenocarcinoma (ADC) and squamous cells carcinoma (SCC) were collected based on their pathological diagnosis.


METHODS
Immunohistochemical (IHC) technique was used to study tissue accumulation of P53, P21, cyclooxygenase-2 (COX-2), glutathione S-transferase-P (GST-Pi) and nitrotyrosine (NT) in patients and controls.


RESULTS
P53 expression was not detected in esophageal tissues from normal and GERD samples, whereas it was found positive in Barrett's, ADC, and SCC samples. P21 positive sample was relatively higher in ADC patients as compared to that in SCC (ADC: 52.6%; SCC: 25%). GST-Pi expression was equally accumulated in all the samples. NT was predominantly expressed in ADC (72.7%). COX-2 expression was significantly higher in Barrett's (60.0%) and ADC (66.6%) as compared to that in GERD, SCC and normal. These data were further confirmed by detecting the scores of immunostainings in all the positive samples.


CONCLUSIONS
The pathological changes in ADC and SCC samples which were associated with increasing frequency of NT and COX-2 provides further evidence for involvement of these inflammatory factors in progression of esophagus cancer.
Allameh
Abdolamir
A
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Islamic Republic of Iran. allameha@modares.ac.ir
Rasmi
Yousef
Y
Nasseri-Moghaddam
Siavosh
S
Tavangar
Seyed Mohammad
SM
Sharifi
Roya
R
Sadreddini
Masoud
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000473:pathology; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007492:Iran; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; C002744:3-nitrotyrosine; D014443:Tyrosine; D051546:Cyclooxygenase 2; D051549:Glutathione S-Transferase pi