TY - JOUR
T1 - Gain of Chromosomal Region 3q26 as a Prognostic Biomarker for High-Grade Cervical Intraepithelial Neoplasia
T2 - Literature Overview and Pilot Study
AU - Koeneman, Margot M.
AU - Ovestad, Irene T.
AU - Janssen, Emiel A. M.
AU - Ummelen, Monique
AU - Kruitwagen, Roy F. P. M.
AU - Hopman, Anton H.
AU - Kruse, Arnold J.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2019/4
Y1 - 2019/4
N2 - Approximately 20-40% of high-grade Cervical Intraepithelial Neoplasia (CIN) regresses spontaneously, but the natural prognosis of an individual lesion is unpredictable. Gain of the chromosomal 3q region, which contains the human telomerase RNA gene on 3q26, is found in CIN lesions and cervical carcinoma and shows correlation with disease grade. The aim of this study is to assess whether 3q26 gain as a single genetic marker can predict the natural prognosis of high-grade CIN, by performing a review of the literature and pilot study. A literature review was conducted. Additionally, we performed a pilot study in 19 patients with histologically confirmed high-grade CIN lesions who were followed for a mean of 115days, after which loop excision was performed. Fluorescent in situ hybridization analysis was performed on the initial diagnostic biopsies to determine gain of 3q26. Eight studies were included in the literature overview, with a total of 407 patients. Of these, only 22 patients had high-grade lesions. All studies found an association between 3q26 gain and disease prognosis. Positive predictive values (PPV) ranged from 50 to 93%, negative predictive values (NPV) ranged from 75 to 100%. Only five out of 155 patients (3.2%) without 3q26 gain showed disease persistence or progression. In our pilot study on3q26 gain inhigh-grade CIN, the PPV of 3q26 gain for disease persistence was 67%, the NPV 100%. All four patients without 3q26 gain showed disease regression. In conclusion, the absence of 3q26 gain in diagnostic biopsies may be applied to identify high-grade CIN lesions with a high probability of disease regression.
AB - Approximately 20-40% of high-grade Cervical Intraepithelial Neoplasia (CIN) regresses spontaneously, but the natural prognosis of an individual lesion is unpredictable. Gain of the chromosomal 3q region, which contains the human telomerase RNA gene on 3q26, is found in CIN lesions and cervical carcinoma and shows correlation with disease grade. The aim of this study is to assess whether 3q26 gain as a single genetic marker can predict the natural prognosis of high-grade CIN, by performing a review of the literature and pilot study. A literature review was conducted. Additionally, we performed a pilot study in 19 patients with histologically confirmed high-grade CIN lesions who were followed for a mean of 115days, after which loop excision was performed. Fluorescent in situ hybridization analysis was performed on the initial diagnostic biopsies to determine gain of 3q26. Eight studies were included in the literature overview, with a total of 407 patients. Of these, only 22 patients had high-grade lesions. All studies found an association between 3q26 gain and disease prognosis. Positive predictive values (PPV) ranged from 50 to 93%, negative predictive values (NPV) ranged from 75 to 100%. Only five out of 155 patients (3.2%) without 3q26 gain showed disease persistence or progression. In our pilot study on3q26 gain inhigh-grade CIN, the PPV of 3q26 gain for disease persistence was 67%, the NPV 100%. All four patients without 3q26 gain showed disease regression. In conclusion, the absence of 3q26 gain in diagnostic biopsies may be applied to identify high-grade CIN lesions with a high probability of disease regression.
KW - hTERC
KW - 3q26
KW - Cervical intraepithelal neoplasia
KW - Prognosis
KW - Biomarker
KW - IN-SITU HYBRIDIZATION
KW - LOCAL IMMUNE-RESPONSE
KW - TELOMERASE GENE TERC
KW - HUMAN-PAPILLOMAVIRUS
KW - EPITHELIAL BIOMARKERS
KW - NATURAL-HISTORY
KW - EARLY EVENTS
KW - PROGRESSION
KW - REGRESSION
KW - DYSPLASIA
U2 - 10.1007/s12253-018-0480-y
DO - 10.1007/s12253-018-0480-y
M3 - Article
C2 - 30361910
SN - 1219-4956
VL - 25
SP - 549
EP - 557
JO - Pathology & oncology Research
JF - Pathology & oncology Research
IS - 2
ER -