Detection of human papillomavirus and relevant tumor suppressors and oncoproteins in laryngeal tumors.
OBJECTIVE
The mechanism of larynx oncogenesis is complex and controlled by various factors, most of them involved in cell proliferation and apoptosis. In this study, we evaluated the levels of two suppressor proteins (pRb and p53) and two oncogenic proteins (c-Myc and Bcl-2), as well as the apoptotic levels and the presence of human papillomavirus (HPV) in both tumor types.


METHODS
Low- or high-risk HPV viral DNA was determined by PCR and in situ PCR; the level of cellular proteins was examined by immunohistochemistry; the presence of apoptotic cells was evaluated by in situ cell death detection.


RESULTS
Most laryngeal papillomatosis samples contained low-risk HPV determined by both techniques. However, 25% of laryngeal carcinoma samples were positive for HPV employing PCR or in situ PCR. In papillomatosis, pRb and p53 levels were higher than in normal larynxes, whereas laryngeal cancer presented the lowest levels. c-Myc oncogene expression was very low in normal and cancer tissues but highly increased in papillomatosis. Bcl-2 expression was low and showed no significant difference between laryngeal papillomatosis and normal larynxes. By contrast, Bcl-2 was clearly up-regulated in cancer. Normal larynx samples and those from laryngeal papillomatosis exhibited similar relatively high numbers of apoptotic cells, whereas in malignant tumors, these cells were scarce.


CONCLUSIONS
Our results suggest that HPV is an important risk factor in papillomatosis and in some malignant larynx tumors with a strong participation of cellular genes, specifically involved in proliferation and apoptosis. In benign papillomatosis lesions but not in larynx cancer, high p53 activity might preserve the apoptosis process. In larynx cancer, low p53 levels and high bcl-2 expression may be playing an important role to block apoptosis.
Manjarrez
María E
ME
Instituto Nacional de Enfermedades Respiratorias, Tlalpan, México. e_manjarrez@yahoo.com
Ocadiz
Rodolfo
R
Valle
Leticia
L
Pacheco
Cesar
C
Marroquin
Alberto
A
De la Torre
Carlos
C
Selman
Moisés
M
Gariglio
Patricio
P
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010212:Papilloma / Q000235:genetics* / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004279:DNA, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53