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Detection of mRNA of CDKN2A, MKi67 and TOP2A in liquid-based cytology as biomarker of high grade lesions of uterine cervix
  1. N Carreras Diéguez1,
  2. C Martí1,
  3. A Rodríguiez-Trujillo1,
  4. E Barnadas2,
  5. A Torné1,
  6. J Ordi3 and
  7. M del Pino1
  1. 1Gynecology and Obstetrics, Hospital Clinic Barcelona
  2. 2IDIBAPS, Hospital Clínic de Barcelona
  3. 3Pathology Department, Hospital Clinic Barcelona, Barcelona, Spain


Introduction/Background It has been suggested that the evaluation of the expression of host-cell genes involved in cervical carcinogenesis induced by high-risk human papillomavirus (HR-HPV) may be useful to identify patients harbouring high-grade squamous intraepithelial lesions (HSIL). We aimed to evaluate the performance of mRNA detection of three biomarkers (CDKN2A, MKi67, TOP2A) in liquid-based cytology (LBC) to identify HSIL.

Methodology Observational prospective study including 250 patients referred to colposcopy. Patients underwent Pap-test, HR-HPV testing, colposcopy, and at least one biopsy. CDKN2A, MKi67 and TOP2A mRNA was detected in LBC specimens by reverse transcription and quantitative polymerase chain reaction.

Among HR-HPV positive patients, 49 showed negative pathological findings, 38 harboured low-grade squamous intraepithelial lesions (LSIL), 105 harboured HSIL, and 17 showed discordant results between cytology (HSIL) and biopsy (LSIL). Thirty-five patients were HR-HPV negative and presented negative biopsies (control group).

mRNA expression was quantified using ΔCycle threshold and compared between groups. We performed ROC analysis and computed sensitivity and specificity of mRNA expression for HSIL detection.

Results Two hundred and forty-three (97.2%) LBC samples yielded adequate material for mRNA determination.

We found higher expression of the three biomarkers in HSIL group compared to control group (p<0.05). TOP2A expression was higher in HSIL group compared with women with positive HR-HPV testing and negative biopsy (p<0.05). Patients with discordant results between cytology and biopsy, showed higher expression of all biomarkers compared with the control group (p<0.05).

Table 1 shows area under the curve (AUC), sensitivity and specificity of the biomarkers for HSIL detection, at the optimal cut-off point according to ROC curve.

Abstract – Table 1

Area under the curve (AUC), sensitivity and specificity of CKN2A, MKi67 and TOP2A for HSIL detection

Conclusion Detection of mRNA of CKN2A, MKi67 and TOP2A in LBC samples showed higher sensitivity than Pap-test to identify women with HSIL. Further studies are needed to confirm that host-cell mRNA detection might have a role in secondary prevention of cervical cancer.

Disclosure Nothing to disclose.

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