nach oben

Erschienen in:

29.11.2018 | General Gynecology

Sec62/Ki67 dual staining in cervical cytology specimens: a new marker for high-grade dysplasia

verfasst von: Ferenc Zoltan Takacs, Julia Caroline Radosa, Rainer Maria Bohle, Florian Bochen, Ingolf Juhasz-Böss, Erich-Franz Solomayer, Bernard Schick, Maximilian Linxweiler

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

In the previous studies, we demonstrated that Sec62 is essential for tumor cell migration, epithelial-to-mesenchymal transition, and intracellular stress tolerance. An increase in Sec62 expression correlated with an increase in cervical dysplasia severity in liquid-based cytology specimens. Ki67 is an established proliferation marker. Thus, in this study, we examined a method of Sec62/Ki67 dual staining for the detection of high-grade dysplasia and cancer in cervical liquid-based cytology specimens.

Methods

Sec62/Ki67 dual staining was performed on 100 cervical liquid-based cytology specimens. The staining results were correlated with cytological, immunocytological (p16/Ki67), colposcopic, and histological findings.

Results

All 56 (n = 56, 100%) cases of cervical intraepithelial neoplasia grade 3 and cervical cancer (CIN3+ lesions) were positive for Sec62/Ki67 staining, while low-grade lesions and normal cells were negative. Sec62/Ki67 staining was highly sensitive and specific for the detection of CIN2+ and CIN3+ lesions (94.37%; 100% and 100%; 84.09%, respectively).

Conclusions

Sec62/Ki67 dual-staining immunocytochemistry is a promising cytological tool for interpreting high-grade squamous lesions in cytological specimens and for assessing the risk of progression to cancer.

Parkin DM, Stjernswärd J, Muir CS (1984) Estimates of the worldwide frequency of twelve major cancers. Bull World Health Organ 62:163–182PubMedPubMedCentral

Laara E, Day N, Hakama M (1987) Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet 329:1247–1249CrossRef

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:359–386CrossRef

Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, Matchar DB (2000) Accuracy of the papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 132:810–819CrossRefPubMed

Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T (1998) Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia. Pathol Int 48:580–585CrossRefPubMed

Schmidt D, Bergeron C, Denton KJ, Ridder R (2011) p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology. Cancer Cytopathol 119:158–166CrossRefPubMed

Petry KU, Schmidt D, Scherbring S, Luyten A, Reinecke-Lüthge A, Bergeron C, Kommoss F, Löning T, Ordi J, Regauer S, Ridder R (2011) Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 dual-stained cytology. Gynecol Oncol 121:505–509. https://doi.org/10.1016/j.ygyno.2011.02.033 CrossRefPubMed

Bergeron C, Ikenberg H, Sideri M, Denton K, Bogers J, Schmidt D, Alameda F, Keller T, Rehm S, Ridder R (2015) Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results. Cancer Cytopathol 123:373–381CrossRefPubMed

Shroyer KR, Homer P, Heinz D, Singh M (2006) Validation of a novel immunocytochemical assay for topoisomerase II-alpha and minichromosome maintenance protein 2 expression in cervical cytology. Cancer Cytopathol 108:324–330CrossRef

10.

Tosuner Z, Türkmen I, Arici S, Sӧnmez C, Turna S, Onaran Ö (2017) Immunocytoexpression profile of ProExC in smears interpreted as ASC-US, ASC-H, and cervical intraepithelial lesion. J Cytol 34:34–38CrossRefPubMedPubMedCentral

11.

Waldstrøm M, Christensen RK, Ornskov D (2013) Evaluation of p16INK4a/Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion. Cancer Cytopathol 121:136–145CrossRefPubMed

12.

Heselmeyer K, Macville M, Schröck E, Blegen H, Hellström AC, Shah K, Auer G, Ried T (1997) Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. Genes Chromosomes Cancer 19:233–240CrossRefPubMed

13.

Hopman A, Theelen W, Hommelberg P, Kamps M, Herrington C, Morrison L, Speel E-J, Smedts F, Ramaekers F (2006) Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer. J Pathol 210:412–419CrossRefPubMed

14.

Linxweiler M, Bochen F, Schick B, Wemmert S, Al Kadah B, Greiner M, Hasenfus A, Bohle R-M, Juhasz-Bӧss I, Solomayer E-F, Takacs ZF (2016) Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions. BMC Cancer 16:676CrossRefPubMedPubMedCentral

15.

Wright TC, Compagno J, Romano P, Grazioli V, Verma Y, Kershnar E, Tafas T, Kilpatrick MW (2015) Amplification of the 3q chromosomal region as a specific marker in cervical cancer. Am J Obstetr Gynecol 213(51):e1–e8

16.

Allen DG, Hutchins A-M, Hammet F, White DJ, Scurry JP, Tabrizi SN, Garland SM, Armes JE (2002) Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers. Br J Cancer 86:924–928CrossRefPubMedPubMedCentral

17.

Dehan E, Ben-Dor A, Liao W, Lipson D, Frimer H, Rienstein S, Simansky D, Krupsky M, Yaron P, Friedman E et al (2007) Chromosomal aberrations and gene expression profiles in non-small cell lung cancer. Lung Cancer 56:175–184CrossRefPubMed

18.

Chang YC, Yeh K-T, Liu T-C, Chang J-G (2010) Molecular cytogenetic characterization of esophageal cancer detected by comparative genomic hybridization. J Clin Lab Anal 24:167–174CrossRefPubMed

19.

Haverty PM, Hon LS, Kaminker JS, Chant J, Zhang Z (2009) High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors. BMC Med Genom 2:21CrossRef

20.

Sheu JJ-C, Lee C-H, Ko J-Y, Tsao GS, Wu C-C, Fang C-Y, Tsai F-J, Hua C-H, Chen C-L, Chen J-Y (2009) Chromosome 3p12. 3–p14. 2 and 3q26. 2–q26. 32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma. Cancer Epidemiol Prev Biomark 18:2709–2716CrossRef

21.

Linxweiler M, Linxweiler J, Barth M, Benedix J, Jung V, Kim Y-J, Bohle RM, Zimmermann R, Greiner M (2012) Sec62 bridges the gap from 3q amplification to molecular cell biology in non-small cell lung cancer. Am J Pathol 180:473–483CrossRefPubMed

22.

Bochen F, Adisurya H, Wemmert S, Lerner C, Greiner M, Zimmermann R, Hasenfus A, Wagner M, Smola S, Pfuhl T, Bozzato A, Kadah BA, Schick B, Linxweiler M (2017) Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas. Oncotarget 8:4922CrossRefPubMed

23.

Linxweiler M, Schick B, Zimmermann R (2017) Let’s talk about Secs: Sec61, Sec62 and Sec63 in signal transduction, oncology and personalized medicine. Signal Transduct Targeted Ther 2:17002CrossRef

24.

Hagerstrand D, Tong A, Schumacher SE, Ilic N, Shen RR, Cheung HW, Vazquez F, Shrestha Y, Kim SY, Giacomelli AO, Rosenbluh Joseph, Schinzel AC, Spardy NA, Barbie DA, Mermel CH, Weir BA, Garraway LA, Tamayo P, Mesirov JP, Beroukhim R, Hahn WC (2013) Systematic interrogation of 3q26 identifies TLOC1 and SKIL as cancer drivers. Cancer Discov 3:1044–1057CrossRefPubMedPubMedCentral

25.

Greiner M, Kreutzer B, Jung V, Grobholz R, Hasenfus A, Stöhr RF, Tornillo L, Dudek J, Stöckle M, Unteregger G, Kamradt J, Wullich B, Zimmermann R (2011) Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells. Int J Cancer 128:2284–2295. https://doi.org/10.1002/ijc.25580 CrossRefPubMed

26.

Linxweiler M, Schorr S, Schäuble N, Jung M, Linxweiler J, Langer F, Schäfers H-J, Cavalié A, Zimmermann R, Greiner M (2013) Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells. BMC Cancer 13:574CrossRefPubMedPubMedCentral

27.

Trunk MJ, Dallenbach-Hellweg G, Ridder R, Petry KU, Ikenberg H, Schneider V, von Knebel Doeberitz M (2004) Morphologic characteristics of p16INK4a-positive cells in cervical cytology samples. Acta Cytologica 48:771–782CrossRefPubMed

28.

Lastra RR, Ou JJ, Reilly ME, Lawrence WD, Baloch ZW, Brooks JS, Barroeta JE (2014) Utility of ProExC and IMP3 immunocytochemical staining in atypical glandular cells of undetermined significance in liquid-based cervical cytology. Diagn Cytopathol 42:375–379CrossRefPubMed

29.

Oberg TN, Kipp BR, Vrana JA, Bartholet MK, Fales CJ, Garcia R, McDonald AN, Rosas BL, Henry MR, Clayton AC (2010) Comparison of p16INK4a and ProEx C immunostaining on cervical ThinPrep cytology and biopsy specimens. Diagn Cytopathol 38:564–572. https://doi.org/10.1002/dc.21251 CrossRefPubMed

30.

Konishi I, Fujii S, Nonogaki H, Nanbu Y, Iwai T, Mori T (1991) Immunohistochemical analysis of estrogen receptors, progesterone receptors, Ki-67 antigen, and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix. Cancer 68:1340–1350CrossRefPubMed

31.

Dunton CJ, van Hoeven KH, Kovatich AJ, Oliver RE, Scacheri RQ, Cater JR, Carlson JA (1997) Ki-67 antigen staining as an adjunct to identifying cervical intraepithelial neoplasia. Gynecol Oncol 64:451–455CrossRefPubMed

32.

McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC (2008) Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 9:425–434CrossRefPubMed

33.

Habbema D, Weinmann S, Arbyn M, Kamineni A, Williams AE, de Kok MCM, I, van Kemenade F, Field TS, van Rosmalen J, Brown ML, (2017) Harms of cervical cancer screening in the United States and the Netherlands. Int J Cancer 140:1215–1222CrossRefPubMedPubMedCentral

Titel: Sec62/Ki67 dual staining in cervical cytology specimens: a new marker for high-grade dysplasia
verfasst von: Ferenc Zoltan Takacs
Julia Caroline Radosa
Rainer Maria Bohle
Florian Bochen
Ingolf Juhasz-Böss
Erich-Franz Solomayer
Bernard Schick
Maximilian Linxweiler
Publikationsdatum: 29.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 2/2019
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-018-4981-4

Neu im Fachgebiet Gynäkologie und Geburtshilfe

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

Sec62/Ki67 dual staining in cervical cytology specimens: a new marker for high-grade dysplasia

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Gynäkologie und Geburtshilfe

ICI-Therapie in der Schwangerschaft wird gut toleriert

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Update Gynäkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2019

Neonatal outcomes in term pregnancies treated with antenatal corticosteroids for suspected pre-term labor

Transcervical Foley balloon catheter and vaginal prostaglandin E2 insert combination vs. vaginal prostaglandin E2 insert only for induction of labor at term: a randomized clinical trial

Performance of computerized cardiotocography-based short-term variation in late-onset small-for-gestational-age fetuses and reference ranges for the late third trimester

Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition

Placental abruption and long-term cardiovascular morbidity of the offspring

The reproducibility of the novel utilization of five-dimensional ultrasound and power Doppler in the prediction of endometrial receptivity in intracytoplasmic sperm-injected women: a pilot prospective clinical study

Neu im Fachgebiet Gynäkologie und Geburtshilfe

ICI-Therapie in der Schwangerschaft wird gut toleriert

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Update Gynäkologie