The LAST Guidelines in Clinical Practice

We aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical‐grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis‐associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47–2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30–2.75, p = 0.004), while absence was associated with shorter OS in low‐grade serous carcinomas (HR: 2.95, 95% CI 1.61–5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype‐specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low‐grade serous carcinoma justifies CDK4 inhibition.

The Journal of Pathology CR

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study

Rambau

Vierkant

Intermaggio

et al. 2018

“…Previous study have found that the reproducibility of H&E staining morphological diagnoses by pathologists is poor and that the consistency of CIN2 diagnosis is <50%. 14 The reproducibility of CIN2+ morphological diagnosis in the ASCUS/LSIL Triage Study for Cervical Cancer (ALTS) was only 43%. 15 In another study, two pathologists agreed with 84% and 81%, respectively, for CIN3 diagnosis; for CIN2, the agreement was 13% and 31%, respectively.…”

Section: Discussionmentioning

confidence: 99%

The value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients

Song

et al. 2021

Preprint

Background: This study aims to evaluate the value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China. Methods: In this study, we evaluated the value of p16INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients. Results: Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16INK4a immunostaining was 0.327, 0.323, and 0.926, respectively. Conclusion: Positive p16INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL+ diagnosis of HPV-negative patients with CIN2+.

“…diagnosis is < 50%. 12 The reproducibility of CIN2 + morphological diagnosis in the ASCUS/LSIL Triage Study for Cervical Cancer (ALTS) was only 43%. 13 In another study, two pathologists agreed with 84%…”

Section: Comparison Of Detection Methods For Cervical Precancerous Lementioning

confidence: 99%

The Value of p16INK4a Immunostaining for High-grade Squamous Intraepithelial Lesions in Human Papillomavirus–Negative Patients

Song

et al. 2020

Preprint

Objective This study aims to evaluate the value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China.Methods In this study, we evaluated the value of p16INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients.Results Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16INK4a immunostaining was 0.327, 0.323, and 0.926, respectively.Conclusion Positive p16INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL + diagnosis of HPV-negative patients.