Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression.
BACKGROUND
Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection.


METHODS
Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group.


RESULTS
Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples.


CONCLUSIONS
The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.
Laboratorio de Oncologia Molecular, Unidad de Investigacion Medica en Enfermedades Oncologicas CMN S XXI IMSS, Mexico E-mail : 1307patricia@gmail.com.
Al
A
Gonzalez-Herrera
M
M
Salgado-Bernabe
Ck
C
Velazquez-Velazquez
M
M
Salcedo-Vargas
A
A
Andrade-Manzano
F
F
Avila-Moreno
P
P
Pina-Sanchez
D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000821:virology
D004279:DNA, Viral; C484414:HOXB13 protein, human; C086061:HOXB2 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors