Evaluation of p16INK4a Overexpression in a Large Series of Cervical Carcinomas

Pérez, Cristina; Castillo, Marta; Alemany, Laia; Tous, Sara; Klaustermeier, Joellen; Sanjosé, Sílvia de; Velasco, Julio

doi:10.1097/pgp.0b013e3182774546

Cited by 9 publications

(10 citation statements)

References 33 publications

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“…For example, although not all of the AIS case-comparator studies provided full details, there were at least 4 different p16 clones, 5 different methods of evaluating expression, and 6 different positive-negative cut-off definitions 13, 14, 16, 19, 21, 25, 27–29 . The same was true for the adenocarcinoma case studies 13, 14, 16, 19, 21, 25, 27–29, 40, 41, 44, 46, 47, 51–53, 58, 61 . Thus diagnostic application of these biomarkers in the different case-comparator scenarios will be limited until further studies are conducted which control for misclassification of histotypes and use standardized biomarker scoring and cut offs which are consistently applied and validated.…”

Section: Discussionmentioning

confidence: 59%

“…Of the 9 biomarkers evaluated in the comparison to MDA-GAS, chromogranin, HIK1083, and p16 showed a difference of 50% or more and the widest difference was with HIK1083 (Figure 5). Differences were less than 50% in the comparison of ER (1.00 vs. 1.00) 38, 52 , HIK1083 (0.00 vs. 0.00) 29, 5 ), p16 (0.94 vs. 0.98) 16, 28, 29, 52, 53 , and PR (1.00 vs 1.00) 38, 52 to serous-clear carcinoma. Only CD10 was compared to mesonephric carcinoma and it had a difference of more than 50% (0.00 vs. 0.67 29, 48 ).…”

Section: Resultsmentioning

confidence: 81%

“…PTEN and VILI1 were compared once and only in comparison to mucinous adenocarcinoma. Positivity differences amongst CD10 (0.00 vs. 0.11) 29, 48 , Chromogranin (0.06 vs 0.26) 29 , ER (1.00 vs 0.77) 38, 43, 47, 52, 63 , HIK1083 (0.00 vs. 0.09) 29, 44, 47, 52 , MUC2 (0.00 vs 0.28) 29 , MUC6 (0.05 vs 0.26) 29, 44, 47 , p16 (0.94 vs 0.89) 16, 25, 28, 29, 40, 44, 47, 52, 53 , PAX8 (0.42 vs 0.65) 39, 55, 62 , PR (1.00 vs. 0.75) 38, 43, 52, 63 , PTEN (0.91 vs. 0.91) 15 , and VIL1 (0.20 vs. 0.52) 22 were all less than 50% when compared to mucinous adenocarcinoma (heatmap and dendrogram not shown). Of the 9 biomarkers evaluated in the comparison to MDA-GAS, chromogranin, HIK1083, and p16 showed a difference of 50% or more and the widest difference was with HIK1083 (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

“…There was data on the positive expression of 1 or more of 11 biomarkers in adenosquamous carcinoma cases versus the 5 comparators 15, 16, 22, 25, 28, 29, 38, 39, 40, 43, 44, 47, 48, 52, 53, 55, 62, 63 . PTEN and VILI1 were compared once and only in comparison to mucinous adenocarcinoma.…”

Section: Resultsmentioning

confidence: 99%

“…Biomarkers with a 50% plus positivity difference in these remaining analyses were thus: PR 38, 43 for adenosquamous versus endometrioid, CEA 17, 33, 35, 43, 52, 54, 63 and p53 30, 52, 63 for serous-clear cell versus mucinous, CEA 17, 33, 43, 52 and PR 38, 43, 52 for serous-clear cell versus endometrioid, Claudin18 47 , HIK1083 29, 44, 47,52 and p16 16, 25, 28, 29, 40, 44, 47, 52, 53 for MDA-GAS versus mucinous, chromogranin 29 , HIK1083 29, 44, 47, 52 , MUC6 29, 44, 47 , p16 25, 29, 40, 44, 47 , PR 38, 43, 52, 63 , and Vimentin 27, 33, 43 for MDA-GAS versus endometrioid, chromogranin 29 , HIK1083 29, 44, 47, 52 and p16 29, 40, 44, 47, 52, 53 for MDA-GAS versus adenosquamous, CEA 52 , HIK1083 29, 44, 47, 52 , and p16 16, 25, 29, 40, 44, 47, 52 for MDA-GAS versus serous-clear cell, Calretinin 48 and CD10 29, 48 for MDA-GAS versus mesonephric, Calretinin 48 and CD10 29, 48 for mesonephric versus mucinous, CD10 29, 48 for mesonephric versus adenosquamous, and Calretinin …”

Section: Resultsmentioning

confidence: 99%

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Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis

Lee

Rose

Sahasrabuddhe

et al. 2017

International Journal of Gynecological Pathology

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Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.

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Section: Discussionmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis

Lee

Rose

Sahasrabuddhe

et al. 2017

International Journal of Gynecological Pathology

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Early esophageal squamous cell carcinoma in a western series is not associated with active HPV infection

et al. 2020

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Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions

Bernreuther

Daghigh

Möller

et al. 2020

Pathol. Oncol. Res.

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Secreted frizzled-related protein 4 (SFRP4) controls WNT signaling and is thought to play a role for tumor aggressiveness. Here, we analyzed a tissue microarray containing 11,152 prostate cancers with pathological, clinical and molecular data by immunohistochemistry. SFRP4 expression was higher in cancer than in non-neoplastic acinar cells. SFRP4 staining was seen in 64.9% of tumors and classified as weak in 33.2%, moderate in 23.9% and strong in 7.8% of cancers. SFRP4 overexpression was linked to advanced tumor stage, high classical/quantitative Gleason grade (p < 0.0001 each), lymph node metastasis (p = 0.0002), and a positive surgical margin (p = 0.0017). SFRP4 positivity was markedly more frequent in ERG positive (77.4%) than in ERG negative cancers (57.4% p < 0.0001). Subset analyses in 2725 cancers with and 3592 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. In a multivariate analysis including various postoperative and prognostic clinico-pathological features, SFRP4 protein expression emerged as an independent prognostic parameter in ERG negative cancers. SFRP4 immunostaining was significantly linked with 10 of 11 previously analyzed chromosomal deletions (p < 0.05 each). In conclusion, high SFRP4 immunostaining is associated with poor prognosis and genomic instability in ERG negative prostate cancers.

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Evaluation of p16INK4a Overexpression in a Large Series of Cervical Carcinomas

Cited by 9 publications

References 33 publications

Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis

Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis

Early esophageal squamous cell carcinoma in a western series is not associated with active HPV infection

Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions

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