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The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions.

Zubillaga-Guerrero MI, Illades-Aguiar B, Leyva-Vazquez MA, Flores-Alfaro E, Castañeda-Saucedo E, Muñoz-Valle JF, Alarcón-Romero LC - J Cytol (2013)

Bottom Line: Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer.In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens.Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Research in Cytopathology and Histoquemical, Academic Unit for Chemical Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico.

ABSTRACT

Background: Cyclin-A and cyclin-E are regulators of G1-S phase of normal cell cycle. Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer.

Aim: To determine the expression of cyclin-A and cyclin-E, types of HR-HPV and physical state of DNA in cytologies with the diagnosis of low-grade squamous intraepithelial lesion (LSIL).

Materials and methods: 115 cytological specimens in liquid base (liquid-PREP(™)) were analyzed. 25 specimens were with no signs of SIL (NSIL) and without HPV; 30 with NSIL with low-risk HPV (LR-HPV); 30 with NSIL with HR-HPV; and 30 with both LSIL and HR-HPV. The expression of cyclins was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV. The physical state of HPV was evaluated by in situ hybridization with amplification with tyramide.

Results: In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens. Among the specimens of NSIL with HR-HPV, 33.3% expressed cyclin-A and 40% cyclin-E, while 100% of the LSILs expressed the 2 cyclins. On the other hand, 100% of the samples NSIL with LR-HPV presented an episomal pattern. Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed. Among the LSILs, 90% were mixed and 10% integrated.

Conclusions: The cyclins A and E are present in the LSILs that occur predominantly in mixed state in the presence of HR-HPV.

No MeSH data available.


Related in: MedlinePlus

Physical state HPV-16 DNA and expression of cyclin A and E; (a) Specimen NSIL, showing normal cells that presented as an episomal pattern (black arrow); (b) Specimen LSIL showing cells with karyomegaly presented as an integrated pattern (black arrow); (c) Positive for cyclin A expression, cells intermediate with karyomegaly (black arrows); (d) Expression of cyclin E positive, cells intermediate with binucleation and karyomegaly (black arrows). (Technique: In situ hybridization with tyramide amplification, ×400 and ×1000; Streptavidin biotin peroxidase, ×400)
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Figure 1: Physical state HPV-16 DNA and expression of cyclin A and E; (a) Specimen NSIL, showing normal cells that presented as an episomal pattern (black arrow); (b) Specimen LSIL showing cells with karyomegaly presented as an integrated pattern (black arrow); (c) Positive for cyclin A expression, cells intermediate with karyomegaly (black arrows); (d) Expression of cyclin E positive, cells intermediate with binucleation and karyomegaly (black arrows). (Technique: In situ hybridization with tyramide amplification, ×400 and ×1000; Streptavidin biotin peroxidase, ×400)

Mentions: A total of 9 HR-HPV genotypes were identified: 16, 18, 31, 35, 39, 45, 52, 58 and 59. HPV-16 was most frequent in NSIL (60%) and LSIL (53%) cytologies (P < 0.001). 90% of the LR-HPV specimens exhibited HPV-6 and only 10% corresponded to type 11 (data not shown). In 100% of the specimen with NSIL with LR-HPV, viral DNA was found in episomal form in a scant number of cells, while for the specimens NSIL with HR-HPV, the episomal state was observed in 56.6% of the cases [Figure 1a], mixed in 20% and integrated in 23.3%. For the specimens with LSIL and HR-HPV, 90% presented a mixed pattern and 10% an integrated pattern [Figure 1b].


The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions.

Zubillaga-Guerrero MI, Illades-Aguiar B, Leyva-Vazquez MA, Flores-Alfaro E, Castañeda-Saucedo E, Muñoz-Valle JF, Alarcón-Romero LC - J Cytol (2013)

Physical state HPV-16 DNA and expression of cyclin A and E; (a) Specimen NSIL, showing normal cells that presented as an episomal pattern (black arrow); (b) Specimen LSIL showing cells with karyomegaly presented as an integrated pattern (black arrow); (c) Positive for cyclin A expression, cells intermediate with karyomegaly (black arrows); (d) Expression of cyclin E positive, cells intermediate with binucleation and karyomegaly (black arrows). (Technique: In situ hybridization with tyramide amplification, ×400 and ×1000; Streptavidin biotin peroxidase, ×400)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643354&req=5

Figure 1: Physical state HPV-16 DNA and expression of cyclin A and E; (a) Specimen NSIL, showing normal cells that presented as an episomal pattern (black arrow); (b) Specimen LSIL showing cells with karyomegaly presented as an integrated pattern (black arrow); (c) Positive for cyclin A expression, cells intermediate with karyomegaly (black arrows); (d) Expression of cyclin E positive, cells intermediate with binucleation and karyomegaly (black arrows). (Technique: In situ hybridization with tyramide amplification, ×400 and ×1000; Streptavidin biotin peroxidase, ×400)
Mentions: A total of 9 HR-HPV genotypes were identified: 16, 18, 31, 35, 39, 45, 52, 58 and 59. HPV-16 was most frequent in NSIL (60%) and LSIL (53%) cytologies (P < 0.001). 90% of the LR-HPV specimens exhibited HPV-6 and only 10% corresponded to type 11 (data not shown). In 100% of the specimen with NSIL with LR-HPV, viral DNA was found in episomal form in a scant number of cells, while for the specimens NSIL with HR-HPV, the episomal state was observed in 56.6% of the cases [Figure 1a], mixed in 20% and integrated in 23.3%. For the specimens with LSIL and HR-HPV, 90% presented a mixed pattern and 10% an integrated pattern [Figure 1b].

Bottom Line: Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer.In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens.Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Research in Cytopathology and Histoquemical, Academic Unit for Chemical Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico.

ABSTRACT

Background: Cyclin-A and cyclin-E are regulators of G1-S phase of normal cell cycle. Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer.

Aim: To determine the expression of cyclin-A and cyclin-E, types of HR-HPV and physical state of DNA in cytologies with the diagnosis of low-grade squamous intraepithelial lesion (LSIL).

Materials and methods: 115 cytological specimens in liquid base (liquid-PREP(™)) were analyzed. 25 specimens were with no signs of SIL (NSIL) and without HPV; 30 with NSIL with low-risk HPV (LR-HPV); 30 with NSIL with HR-HPV; and 30 with both LSIL and HR-HPV. The expression of cyclins was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV. The physical state of HPV was evaluated by in situ hybridization with amplification with tyramide.

Results: In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens. Among the specimens of NSIL with HR-HPV, 33.3% expressed cyclin-A and 40% cyclin-E, while 100% of the LSILs expressed the 2 cyclins. On the other hand, 100% of the samples NSIL with LR-HPV presented an episomal pattern. Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed. Among the LSILs, 90% were mixed and 10% integrated.

Conclusions: The cyclins A and E are present in the LSILs that occur predominantly in mixed state in the presence of HR-HPV.

No MeSH data available.


Related in: MedlinePlus