p16 immunohistochemistry interpretation

Results p16 over expression was noted in 22.9% (33 cases), while 21.5% (31 cases) were focal positive and 55.6% (80 cases) were negative for p16 over expression. p16^INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated cervical precancerous lesions. The interpretive variability of cervical biopsies and its relationship to HPV status. Boslooper K, Lam AK, Gao J, Weinstein S, Johnson N. The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma. Smeets SJ, Plas M, Schaaij-Visser T, Veen E, Meerloo J, Braakhuis B, et al. Cases with diffuse p16 staining, that is continuous staining comprising the basal and parabasal cell layers of the squamous epithelium, were considered positive for p16 IHC, based on the criteria described in more detail by Stoler et al11; cases with either focal staining or no staining were considered negative for p16 IHC. Beck TN, Smith CH, Flieder DB, Galloway TJ, Ridge JA, Golemis EA, Mehra R. Head Neck. Formalin fixation leads to robust, easily interpretable p16 staining in cell blocks. The 4 individual reading sets were assigned to the 4 different reader cohorts (1 reading set per reader cohort). Routine use of adjunctive. For example, Thrall13 found that when their laboratory switched from using p16 IHC sporadically to performing p16 IHC according to the LAST criteria that the use of p16 IHC increased and this increase was accompanied by a significant increase in the proportion of women diagnosed with CIN2,3. Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia. Retrieved from "https: . Hashmi AA, Iftikhar SN, Haider R, Baig NN, Asif MG, Irfan M. Cureus. When stratified in this manner marked differences were observed in the impact of p16 IHC. p16 IHC performed on all cervical biopsies improves the diagnostic performance of ISPs and will help prevent errors in clinical management. government site. Correlation of P16 expression with various clinical factors. Before The .gov means its official. Bookshelf Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). J Low Genit Tract Dis. 2010 Dec;134(12):1785-92. doi: 10.5858/2009-0522-RAR.1. Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer. Most of the cases included in the present study were tobacco chewers (86%), paan chewers (60%), nonalcoholic (76%) and without multiple sexual partners (76%). It should be noted that there were fewer diagnoses of CIN2+ made using ISPH&E+p16/LAST compared with ISPH&E, 3773 versus 3996, respectively. Shain AF, Kwok S, Folkins AK, et al. Data Sources. Agreement rates of ISPs diagnoses on H&E versus on H&E+p16/LAST with both CPR reference diagnoses dichotomized at the CIN2+ threshold are shown in Table 3. Human papillomavirus (HPV) type 16 has also been suggested to play a role in the etiology of head-and-neck squamous cell carcinoma (HNSCC). Please try after some time. The site is secure. Table 4 illustrates the correlation of p16 expression with lymphadenopathy. 2014 Dec;142(6):767-72. doi: 10.1309/AJCP3TPHV4TRIZEK. 2018;433:11. Peltonen JK, Helppi HM, Pkk P, Turpeenniemi-Hujanen T, Vhkangas KH. Chapter First Online: 06 May 2022 Abstract Immunohistochemistry (IHC) is a technique whereby antigens (proteins) that are present in a cell are detected by the use of antibodies that bind to the antigens. 7. [13,22], However, in study by Yuen et al. 3. 11,20,21 Recommendations . to maintaining your privacy and will not share your personal information without P16 Cutoff in Head and Neck Squamous Cell Carcinoma: Correlation P < 0.05 was taken as significant and <0.01 as highly significant; whereas P > 0.05 was taken as nonsignificant. Current Updates on Cancer-Causing Types of Human Papillomaviruses (HPVs) in East, Southeast, and South Asia. The Bill & Melinda Gates Foundation and the NIH Fogarty International Clinical Research Scholars Program (NIH; R24 TW007988) funded this work. p16 Immunohistochemical Expression in Head and Neck Squamous Cell p16 IHC is currently recommended as an adjunctive molecular stain to clarify the diagnosis of CIN2 . Dupont WD, Plummer D, Lewis JS (September 2017). IHC profile of the tumor was assessed by subjecting one representative section from tumor block to p16. Simoens C, Goffin F, Simon P, et al. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. Bcl2 expression in head and neck cancer. Heterogeneity of p16 immunohistochemistry and increased sensitivity of RNA in situ hybridization in cytology specimens of HPV-related head and neck squamous cell carcinoma. 2018;118:16. In both reading rounds, ISPs were provided with information about the respective patients age at the time of biopsy collection, preceding cervical cytology result, and HPV test result (if available). The mean sensitivity and specificity for consensus CIN2+ of p16 IHC as scored by the readers were 88% and 87%, respectively, versus an overall sensitivity and specificity by the pathologist of 96% and 92%, respectively. A number of studies have documented improved sensitivity for detecting CIN2,3 and improved reproducibility among pathologists when p16INK4a immunostaining is utilized in conjunction with H&E-stained slides to diagnose cervical biopsies.811 In an effort to reconcile the multiple and confusing terminologies used for diagnosing cervical biopsies, in 2010 the College of American Pathologists (CAP) and American Society for Colposcopy and Cervical Pathology (ASCCP) organized a terminology standardization project referred to as the Lower Anogenital Squamous Terminology (LAST) Standardization Project. As shown in Table 2, exact agreement of ISP diagnoses as compared with the reference diagnosis CPRH&E+p16 was higher within each diagnostic category (no CIN, CIN1, CIN2, CIN3, and ACIS) when p16 was added to ISP reading per LAST; the exact agreement rate improved from 53.5% (10,284/19,230) for ISPH&E to 57.4% (11,033/19,226) for ISPH&E+p16/LAST. p16 IHC has been shown to be sensitive for CIN2 and CIN3 7,14 and its interpretation is much more reliable/reproducible than morphology based on H&E staining alone. 19. 4. The ISPs who have a diagnostic approach that is balanced between sensitivity and specificity have an 10% difference in PPA with the use of p16 and this also is only minimally impacted by whether or not they requested p16. Objective: Kyrgiou M, Koliopoulos G, Martin-Hirsch P, et al. History of abnormal sexual habit was present in 24 patients, of which 19 (79.17%) were having positive p16 expression. The method of interpretation (nuclear versus cytoplasmic staining) also appears to give differing results, as studies considering only nuclear staining appeared to show more consistent results from study to study. Lentsch G, Valdebran M, Saknite I, Smith J, Linden KG, Knig K, Barr RJ, Harris RM, Tromberg BJ, Ganesan AK, Zachary CB, Kelly KM, Balu M. Pigment Cell Melanoma Res. p53 expression but not p16(INK4A) correlates with human papillomavirus-associated esophageal squamous cell carcinoma in Kazakh population. This provides an opportunity to compare the impact of p16 IHC on cases for which the ISP did not request p16 IHC (non-LAST cases) to its impact in those in which they did request p16 IHC (LAST cases). The average difference in NPA of ISPs in round 2 (H&E+p16) versus round 1 (H&E only) also differs by diagnostic approach, but moves in the opposite direction to PPA. Bergeron C, Ordi J, Schmidt D, et al. 6. Results: to maintaining your privacy and will not share your personal information without Cervical histopathology variability among laboratories: a population-based statewide investigation. It involved 1100 cervical biopsies and 70 ISPs, each of whom read the biopsies twice, once using only H&E-stained slides (ISPH&E) and a second time using both H&E and p16-stained slides (ISPH&E+p16). Keyword Highlighting PDF Interpretation of p16 Immunohistochemistry In Lower Anogenital Tract Loss of tumor suppressor p16 expression in initial stages of oral oncogenesis. For non-LAST cases there was a significant improvement in PPA (ie, sensitivity for CIN2+) when p16 IHC was used, a 5.2% improvement when the reference diagnoses was CPRH&E and an 11% improvement when the reference diagnosis was CPRH&E+p16 (Table 4). 12. is a consultant to Ventana Medical Systems Inc (Roche Tissue Diagnostics). An official website of the United States government. Muirhead DM, Hoffman HT, Robinson RA. and transmitted securely. You may be trying to access this site from a secured browser on the server. Wilson GD, Saunders MI, Dische S, Bentzen SM, Richman PI, Daley FM. 2008;32:502512. Readers were blinded to round 1 reading results. [5] Human papillomavirus (HPV) status is associated with p16 expression, and HPV-positive tumors are less likely to harbor p53 mutations. In summary, these findings have important implications for deciding when to utilize p16 IHC for cervical biopsies. In the present study, grade 3 p16 expression was observed in 19 cases (19%), grade 2 in 18 cases (18%) and grade 1 in 23 cases (23%), while 40 cases (40%) were negative for p16 and scored grade 0. National Library of Medicine p16 Immunohistochemistry is useful in confirming high-grade squamous intraepithelial lesions (HSIL) in women with negative HPV testing It is believed that almost all squamous cell carcinomas of the cervix are associated with HR-HPV infection. Essential information from each study (number of samples, antibody used, collection dates, overall p16 immunohistochemistry results, and general method of interpretation) was tabulated and analyzed. Early-stage tumors are treated with surgery or radiotherapy and have a favorable prognosis. Effect of lower anogenital squamous terminology recommendations on the use of, 14. 21. p16 antibody IHC staining and interpretation. Unable to load your collection due to an error, Unable to load your delegates due to an error. Careers. Some error has occurred while processing your request. Similar to our study, Ralli et al. Sometimes such fragments were away from the actual biopsy. One tertile has relatively high NPAs and relatively low PPAs for CIN2+ compared with the CPR and appears to favor specificity over sensitivity. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The new guidelines proposed by the College of American Pathologists (CAP), for HPV testing in head and neck carcinomas in routine clinical practice proposed the interpretation of p16 IHC as follows: tumors with lack of staining or < 70% of nuclear and cytoplasmic staining are classified as HPV negative, while tumors with 70% of nuclear and . Bookshelf In that laboratory the use of p16 IHC increased from 3.3% of cervical biopsies before using the LAST criteria to 13.9% after the LAST criteria were adopted.13 The initial H&E reads by ISPs for the CERTAIN study took place in 2015 which is 3 years after the first publication of the LAST criteria. Dreyer JH, Hauck F, Barros MHM, Niedobitek G. Appl Immunohistochem Mol Morphol. Second Diagnostic Opinion by Experienced Dermatopathologists in the Setting of a Referral Regional Melanoma Unit Significantly Improves the Clinical Management of Patients With Cutaneous Melanoma. Immunohistochemistry was performed on 4-m thick sections from 10% formalin-fixed paraffin-embedded specimens, according to the streptavidin-biotin immunoperoxidase technique. Received 2020 Jun 14; Revised 2020 Oct 27; Accepted 2021 Jan 7. Equivocal p16 Immunostaining in Squamous Cell Carcinoma of the Head and Highlight selected keywords in the article text. The American Journal of Surgical Pathology45(10):1348-1356, October 2021. -, Immunohistochemical over expression of p53 in head and neck squamous cell carcinoma: clinical and prognostic significance. Twelve nonpathologists of varying educational backgrounds living in Beijing, China received video training and were assigned one of 4 sets of 25 CIN2+ and 25 CIN less severe than CIN2 for evaluation. cervical intraepithelial neoplasia, human papillomavirus, Pap, VIA, p16INK4a, immunohistochemistry. A pathologist reviewed all 100 cases. Correlation of p16 expression with lymphadenopathy. 2015;39:729736. 3). -. Out of 60% positive cases, 23 (23%) showed Grade 1 (low expression) [Figure 6], 18 (18%) showed Grade 2 (moderate expression) [Figure 7] and 19 (19%) showed Grade 3 (strong expression) [Figure 8] p16 expression. This increase in the detection of histologic HSIL cases came at the cost of a slight, but statistically significant decrease in NPA (0.8%; 95% CI, 1.1 to 0.5; P<0.0001) when p16 was used in the subset of non-LAST cases in this study (Table 4; Fig. The mean age of the males and females was 46.03 14.33 years and 50.08 14.91 years, respectively. All 70 ISPs who participated in this study were (i) board-certified in anatomic pathology, (ii) licensed and currently practicing medicine in the United States, and (iii) evaluate cervical histology specimens as part of their routine clinical practice. Examples of representative cases showing p16 immunostaining pattern are also illustrated. 2020 Nov 8;12(11):e11385. During the first reading round on H&E-stained slides only, both ISPs as well as the gynecologic pathologists establishing the CPR-derived reference diagnoses were asked whether, based on their review on H&E, they would request adjunctive p16 IHC staining according to LAST criteria as follows: (i) an H&E morphologic differential diagnosis between precancer (CIN2 or CIN3) and a mimic of precancer, (ii) an H&E morphologic interpretation of CIN2 that is or was entertained, and (iii) an H&E morphologic interpretation of CIN1 but at high risk for missed high-grade disease, defined as a prior cytologic interpretation of HSIL, ASC-H, or AGC (not otherwise specified). [24], In our study, a maximum number of cases belonged to histologic grade I (61%), which was in concordance to study by Chen et al. Yuen AP, Lam KY, Choy JT, Ho WK, Wong LY, Wei WI. Journal of Oral and Maxillofacial Pathology : JOMFP. All 17 or 18 ISPs within 1 reader cohort read all 275 specimens assigned to the respective cohort of readers. Castle PE, Adcock R, Cuzick J, et al. To evaluate the effect of the current clinical recommendations calling for the use of adjunctive p16 IHC staining, the 70 ISP readers were requested to specify for each case during the initial interpretation of the H&E-stained slides in round 1 whether they would order adjunctive p16 IHC, based on the available set of LAST criteria. Thrall MJ. Materials and methods: [9] As with female genital (or cervical) carcinogenesis, the immunohistochemical detection of p16 protein (p16 IHC) has been proposed as a surrogate marker of HPV infection in HNC.[10]. Well-differentiated squamous cell carcinoma showing keratin pearls and intracytoplasmic keratinization (H&E, 100), Moderately differentiated squamous cell carcinoma showing intracytoplasmic keratinization and moderate nuclear pleomorphism (H&E, 400), Poorly differentiated squamous cell carcinoma showing clusters of highly pleomorphic tumor cells with hyperchromatic nucleus and fair number of mitotic figures (H&E, 200).
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