The association of p16(INK4A) and fragile histidine triad gene expression and cervical lesions.
OBJECTIVE
This cross-sectional study was intended to assess the association between immunohistochemical analysis of p16 and fragile histidine triad (FHIT) and the presence of precancerous cervical lesions.


METHODS
Women seen at Pérola Byington Hospital, São Paulo, Brazil, with histologically confirmed cervicitis (n = 31), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2,3 (n = 30), and cervical cancer (n = 7) had also cervical material collected for liquid-based cytology, human papillomavirus Hybrid Capture 2 (HC2) test, and p16 and FHIT immunohistochemical reactions.


RESULTS
p16 and FHIT reactions were scored as the following: <1%, 1% to 5%, >5% to 25%, and >25%. Receiver operating curve analysis was used to select p16 and FHIT score cutoffs for further categorical analyses. All but one of the 37 CIN 2,3/cancer cases had a p16 score of greater than 1% to 5%. Among the 61 cervicitis/CIN 1 cases, 46 (75%) had a p16 score lower than 1% to 5%. In contrast, no association of FHIT expression and severity of cervical lesions could be demonstrated in this data set. Receiver operating curve analyses suggested the score of 1% to 5% for p16 as the cutoff that best discriminates CIN 2,3/cancer from cervicitis/CIN 1. No cutoff for FHIT scores could be suggested with data set.


CONCLUSIONS
p16, but not FHIT expression, has the potential to be used as complementary diagnostic tool to investigate human papillomavirus-induced cervical lesions, if these results are confirmed in larger studies.
Longatto-Filho
Adhemar
A
Pathology Division of Adolfo Lutz Institute, São Paulo, Brazil. longatto@ecsaude.uminho.pt
Etlinger
Daniela
D
Pereira
Sônia Maria Miranda
SM
Kanamura
Cristina Takami
CT
di Loreto
Celso
C
Santos
Gilda da Cunha
Gda C
Makabe
Sérgio
S
Marques
José A
JA
Santoro
Carmen L F
CL
das Dores
Gerson Botacini
GB
Castelo
Adauto
A
D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D052685:Alphapapillomavirus; D019540:Area Under Curve; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*; D002575:Uterine Cervicitis / Q000235:genetics / Q000378:metabolism*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase