High prevalence of p16 staining in malignant tumors
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High prevalence of p16 staining in malignant tumors. / De Wispelaere, Noémi; Rico, Sebastian Dwertmann; Bauer, Marcus; Luebke, Andreas M; Kluth, Martina; Büscheck, Franziska; Hube-Magg, Claudia; Höflmayer, Doris; Gorbokon, Natalia; Weidemann, Sören; Möller, Katharina; Fraune, Christoph; Bernreuther, Christian; Simon, Ronald; Kähler, Christian; Menz, Anne; Hinsch, Andrea; Jacobsen, Frank; Lebok, Patrick; Clauditz, Till; Sauter, Guido; Uhlig, Ria; Wilczak, Waldemar; Steurer, Stefan; Burandt, Eike; Krech, Rainer; Dum, David; Krech, Till; Marx, Andreas; Minner, Sarah.
in: PLOS ONE, Jahrgang 17, Nr. 7, e0262877, 2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High prevalence of p16 staining in malignant tumors
AU - De Wispelaere, Noémi
AU - Rico, Sebastian Dwertmann
AU - Bauer, Marcus
AU - Luebke, Andreas M
AU - Kluth, Martina
AU - Büscheck, Franziska
AU - Hube-Magg, Claudia
AU - Höflmayer, Doris
AU - Gorbokon, Natalia
AU - Weidemann, Sören
AU - Möller, Katharina
AU - Fraune, Christoph
AU - Bernreuther, Christian
AU - Simon, Ronald
AU - Kähler, Christian
AU - Menz, Anne
AU - Hinsch, Andrea
AU - Jacobsen, Frank
AU - Lebok, Patrick
AU - Clauditz, Till
AU - Sauter, Guido
AU - Uhlig, Ria
AU - Wilczak, Waldemar
AU - Steurer, Stefan
AU - Burandt, Eike
AU - Krech, Rainer
AU - Dum, David
AU - Krech, Till
AU - Marx, Andreas
AU - Minner, Sarah
PY - 2022
Y1 - 2022
N2 - p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis.
AB - p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis.
KW - Biomarkers, Tumor/metabolism
KW - Carcinoma, Squamous Cell/pathology
KW - Carcinoma, Transitional Cell/complications
KW - Cyclin-Dependent Kinase Inhibitor p16/metabolism
KW - DNA, Viral
KW - Female
KW - Humans
KW - Papillomaviridae/genetics
KW - Papillomavirus Infections
KW - Prevalence
KW - Staining and Labeling
KW - Urinary Bladder Neoplasms/complications
U2 - 10.1371/journal.pone.0262877
DO - 10.1371/journal.pone.0262877
M3 - SCORING: Journal article
C2 - 35862385
VL - 17
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 7
M1 - e0262877
ER -
