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Combined assessment of 3q26 amplification and promoter methylation in patients with high grade cervical lesions show age specific differences
Author(s) -
Beiersdorf Josefine,
Scheungraber Cornelia,
Wunsch Kristina,
Schmitz Martina,
Hansel Alfred,
Hoyer Heike,
Gajda Mieczyslaw,
Greinke Christiane,
Runnebaum Ingo B.,
Dürst Matthias,
Backsch Claudia
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22818
Subject(s) - medicine , methylation , bonferroni correction , cervical intraepithelial neoplasia , cohort , oncology , dna methylation , gastroenterology , cervical cancer , cancer , biology , gene , genetics , gene expression , statistics , mathematics
Abstract A considerable proportion of high grade cervical intraepithelial lesions (CIN2/3) are known to resolve on their own especially among young women. However, since reliable prognostic markers are still lacking, the diagnosis “CIN3” is still an indication for surgery which may result in overtreatment. It is conceivable that a combination of different, ideally independent molecular markers may provide more reliable results. In the present cross‐sectional study two established triage markers, 3q26 amplification and a methylation signature, were evaluated in an age‐dependent manner. The patient cohort comprised 60 patients with histologically confirmed CIN2/3 in two equally sized age groups (<30 years, ≥30 years). Cervical scrapes were analyzed by interphase fluorescence in situ hybridization for 3q26 amplification and methylation specific PCR (GynTect®) for six different genome regions. Both assays showed a significantly different pattern of test outcome independent of age ( P = .001). Moreover, the combination of both assays differed significantly for double positive and double negative cases when comparing the two age groups: In patients <30 years there were clearly less cases with positive methylation signature and amplification of 3q26 as in women ≥30 years (23% vs 63%, Bonferroni adjusted P = .016). Of particular interest is the finding that double negative results were exclusive for the young age group (0% vs 27%, Bonferroni adjusted P = .020). Since regression of CIN2/3 characteristically occurs among young women it is tempting to speculate that a double negative test result could be prognostic for regression of CIN2/3. This will have to be investigated further in a prospective longitudinal intervention study.

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