Utility of p16/Ki67 double immunocytochemistry for detection of cervical adenocarcinoma

Abstract

BACKGROUND:Although the incid ence of cervical ad enocarcinoma has consistently increased , especially among young women, there is no established best means for screening. This study evaluated the screening efficacy of CINtec PLUS (CINtec; p16/Ki67 d ouble immunocytochemistry) expression in cervical gland ular cells. METHODS: Cervical cytology was examined using abnormal gland ular cells. The CINtec status of 100 samples with correspond ing surgically resected specimens and 11 samples that exhibited negative results for intraepithelial lesion or malignancy at follow-up was analyzed . Ad d itionally, 31 negative samples containing benign glandular cells were included. RESULTS: Of the 142 samples, CINtec status was diffusely positive in 74, focally positive in 24, and negative in 44. The 74 d iffusely positive samples includ ed 70 ad enocarcinomas (62 cervical, seven uterine, and one ovarian) and four cases of high-grad e cervical intraepithelial neoplasia. The 24 focally positive samples included 15 adenocarcinomas (seven cervical, seven uterine, and one fallopian tube) and nine without malignancy. The 44 negative samples included nine adenocarcinomas (five uterine and four cervical) and 35 without malignancy.The sensitivity, specificity, positive predictive value, and negative predictive value of the CINtec diffusely or focally positive cases for cervical adenocarcinomas were 94.5%, 58.0%, 70.4%, and 90.9%, respectively. In CINtec diffusely positive cases, the respective values were 84.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment—Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology

“…In this regard, some methods could further increase this value. In an exciting study using CINtec PLUS (CINtec; p16/Ki67 double immunocytochemistry), it was reported that when it was diffusely positive, it was able to achieve accuracy values for glandular lesions of 84.9% (sensitivity), 82.6% (specificity), 83.8% (positive predictive value), and 83.8% (negative predictive value) [ 37 ]. An additional test, such as APTIMa mRNA, has shown good accuracy in identifying glandular lesions of the uterine cervix [ 38 ].…”

P16/Ki67 Dual Staining in Glandular Cell Abnormalities of the Uterine Cervix

“…However, the majority of the studies performed in the past focused on the utility of p16/Ki67 DS on squamocellular cytologic changes. Only very limited information exists about the usefulness of p16/KI67 in the detection of glandular cervical precancerous lesions and cervical adenocarcinoma [17]. The detection of glandular precancerous lesions by cervical cytology or by colposcopy is often prevented by the presence of a glandular lesion at the base of the crypts and by the often-multifocal nature of adenocarcinoma in situ (AIS) [10,17].…”

“…Only very limited information exists about the usefulness of p16/KI67 in the detection of glandular cervical precancerous lesions and cervical adenocarcinoma [17]. The detection of glandular precancerous lesions by cervical cytology or by colposcopy is often prevented by the presence of a glandular lesion at the base of the crypts and by the often-multifocal nature of adenocarcinoma in situ (AIS) [10,17]. Therefore, a method to increase the reliability of cervical cytology in detecting glandular lesions would be very helpful, especially in light of the increasing incidence of cervical adenocarcinoma [18].…”

Immunoreactivity of TTF‐1, GATA‐3, CEA, and p16/Ki67 cocktail in Cellprep®‐processed control samples: Comparison of long‐term storage in vials and slides

“…Using this established dual stain, we have previously demonstrated the utility of CINtec in detecting cervical adenocarcinoma, which is not sufficiently detectable by the Pap test alone. 8 Cell blocks allow the immunostaining of samples using the same protocol as formalin-fixed and paraffin-embedded (FFPE) sections but require an adequate sample volume to prepare. However, in clinical practice, the sample volumes are often limited.…”

“…The p16/Ki67 dual stain, marketed as CINtec® PLUS Cytology (CINtec; Roche Diagnostics), is the only commercially available test using a dual‐biomarker for ICC. Using this established dual stain, we have previously demonstrated the utility of CINtec in detecting cervical adenocarcinoma, which is not sufficiently detectable by the Pap test alone 8 …”