Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival.
The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.
Bahnassy
Abeer A
AA
Department of Pathology, National Cancer Institute, Kaser El-Aini School of Medicine, Cairo University, Fom El-Khalig, Cairo 11796, Egypt.
Zekri
Abdel-Rahman N
AR
Abdallah
Samira
S
El-Shehaby
Amal M R
AM
Sherif
Ghada M
GM
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004273:DNA, Neoplasm / Q000032:analysis; D004534:Egypt / Q000453:epidemiology; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human; C497206:MDM2 protein, human