Prognostic significance of tumor angiogenesis, Ki 67, p53 oncoprotein, epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma--a prospective study.
BACKGROUND
This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC).


METHODS
Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage.


RESULTS
On univariate analysis, EGFR expression correlated with poorer OS (p =.0001), DFS (p =.01), shorter TTP (p =.0001), and advanced T stage (p =.036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p =.04) and shorter TTP in a subgroup of patients with UICC stage III-IV disease. HER2 expression was associated with advanced UICC stage (p =.006). The presence of p53 expression correlated with poorer DFS (p =.01) and a trend toward shorter TTP (p =.06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP.


CONCLUSIONS
EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease.
Ma
Brigette B Y
BB
Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territory, Hong Kong SAR, China.
Poon
Terence C W
TC
To
K F
KF
Zee
Benny
B
Mo
Frankie K F
FK
Chan
Charles M L
CM
Ho
Stephen
S
Teo
Peter M L
PM
Johnson
Phillip J
PJ
Chan
Anthony T C
AT
D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53