P634A4 and TAp73 immunocytochemistry in liquid-based cervical cytology--potential biomarkers for diagnosis and progress prediction of cervical neoplasia.
P63 and p73 are two homologues of the important tumor suppressor gene p53. In this study, we investigated p63 and p73 expression by immunocytochemistry using antibodies for TAp73 and p634A4 isoforms in 91 high-grade and 107 low-grade squamous intraepithelial lesions, 212 atypical squamous cells of undetermined significance, 9 squamous cell carcinomas and 63 normal samples from an Asian screening population together with 47 hospital samples of carcinomas. There was significant correlation between the TAp73 and p634A4 indices (P<0.0001). Significantly, higher TAp73 and p634A4 indices were found in high-grade lesions or carcinoma when compared with atypical squamous cells and low-grade lesions (P<0.0001). Among atypical squamous cells, p634A4 indices of cases that subsequently progressed to low-grade (P=0.031) or high-grade lesions (P=0.006) were significantly higher than those that did not. For atypical squamous cells positive for high-risk human papillomavirus (HPV) as detected by Digene (61%), cases with high p634A4 index were still more likely to have subsequent high-grade lesions detected (P=0.016). Among low-grade lesions, significantly higher TAp73 (P=0.038) was found in cases that subsequently progressed to high-grade lesions. There was significant correlation between presence of high-risk HPV and p634A4 index (P=0.01). In summary, p63 and p73 immunocytochemistry are potential good markers for detection of carcinoma and high-grade lesions in cervical cytology samples and for triage management of women with atypical squamous cells and low-grade lesions.
Cheung
Annie N Y
AN
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. anycheun@hkucc.hku.hk
Tsun
Ka-Lai
KL
Ng
Kin-Man
KM
Szeto
Elaine
E
Siu
Michelle K
MK
Wong
Esther S
ES
Ngan
Hextan Y
HY
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics
D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins