Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications

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@article{8a0aba491c324033a835faa3dd3ea8ab,
title = "Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications",
abstract = "Cytokeratins (CKs) 5 and 6 are functionally unrelated but often analyzed together using bispecific antibodies in diagnostic immunohistochemistry. To better understand the diagnostic utility of CK5 or CK6 alone, tissue microarrays with > 15,000 samples from 120 different tumor types as well as 608 samples of 76 different normal tissues were analyzed by immunohistochemistry. In normal tissues, both CKs occurred in the squamous epithelium; CK5 dominated in basal and CK6 in suprabasal layers. CK5 (not CK6) stained basal cells in various other organs. Within tumors, both CK5 and CK6 were seen in > 95% of squamous cell carcinomas, but other tumor entities showed different results: CK5 predominated in urothelial carcinoma and mesothelioma, but CK6 in adenocarcinomas. Joint analysis of both CK5 and CK6 obscured the discrimination of epithelioid mesothelioma (100% positive for CK5 alone and for CK5/6) from adenocarcinoma of the lung (12.8% positive for CK5 alone; 23.7% positive for CK5/6). CK5 and CK6 expressions were both linked to high grade, estrogen receptor, and progesterone receptor negativity in breast cancer (p < 0.0001 each), grade/stage progression in urothelial cancer (p < 0.0001), and RAS mutations in colorectal cancer (p < 0.01). Useful diagnostic properties which are commonly attributed to CK5/6 antibodies such as basal cell staining in the prostate, distinction of adenocarcinoma of the lung from squamous cell carcinoma and epithelioid mesothelioma, and identification of basal-type features in urothelial cancer are solely driven by CK5. At least for the purpose of distinguishing thoracic tumors, monospecific CK5 antibodies may be better suited than bispecific CK5/6 antibodies.",
author = "Cosima V{\"o}lkel and {De Wispelaere}, No{\'e}mi and S{\"o}ren Weidemann and Natalia Gorbokon and Maximilian Lennartz and Luebke, {Andreas M} and Claudia Hube-Magg and Martina Kluth and Christoph Fraune and Katharina M{\"o}ller and Christian Bernreuther and Patrick Lebok and Clauditz, {Till S} and Frank Jacobsen and Guido Sauter and Ria Uhlig and Waldemar Wilczak and Stefan Steurer and Sarah Minner and Krech, {Rainer H} and David Dum and Till Krech and Marx, {Andreas H} and Ronald Simon and Eike Burandt and Anne Menz",
note = "{\textcopyright} 2021. The Author(s).",
year = "2022",
month = feb,
doi = "10.1007/s00428-021-03204-4",
language = "English",
volume = "480",
pages = "433--447",
journal = "VIRCHOWS ARCH",
issn = "0945-6317",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications

AU - Völkel, Cosima

AU - De Wispelaere, Noémi

AU - Weidemann, Sören

AU - Gorbokon, Natalia

AU - Lennartz, Maximilian

AU - Luebke, Andreas M

AU - Hube-Magg, Claudia

AU - Kluth, Martina

AU - Fraune, Christoph

AU - Möller, Katharina

AU - Bernreuther, Christian

AU - Lebok, Patrick

AU - Clauditz, Till S

AU - Jacobsen, Frank

AU - Sauter, Guido

AU - Uhlig, Ria

AU - Wilczak, Waldemar

AU - Steurer, Stefan

AU - Minner, Sarah

AU - Krech, Rainer H

AU - Dum, David

AU - Krech, Till

AU - Marx, Andreas H

AU - Simon, Ronald

AU - Burandt, Eike

AU - Menz, Anne

N1 - © 2021. The Author(s).

PY - 2022/2

Y1 - 2022/2

N2 - Cytokeratins (CKs) 5 and 6 are functionally unrelated but often analyzed together using bispecific antibodies in diagnostic immunohistochemistry. To better understand the diagnostic utility of CK5 or CK6 alone, tissue microarrays with > 15,000 samples from 120 different tumor types as well as 608 samples of 76 different normal tissues were analyzed by immunohistochemistry. In normal tissues, both CKs occurred in the squamous epithelium; CK5 dominated in basal and CK6 in suprabasal layers. CK5 (not CK6) stained basal cells in various other organs. Within tumors, both CK5 and CK6 were seen in > 95% of squamous cell carcinomas, but other tumor entities showed different results: CK5 predominated in urothelial carcinoma and mesothelioma, but CK6 in adenocarcinomas. Joint analysis of both CK5 and CK6 obscured the discrimination of epithelioid mesothelioma (100% positive for CK5 alone and for CK5/6) from adenocarcinoma of the lung (12.8% positive for CK5 alone; 23.7% positive for CK5/6). CK5 and CK6 expressions were both linked to high grade, estrogen receptor, and progesterone receptor negativity in breast cancer (p < 0.0001 each), grade/stage progression in urothelial cancer (p < 0.0001), and RAS mutations in colorectal cancer (p < 0.01). Useful diagnostic properties which are commonly attributed to CK5/6 antibodies such as basal cell staining in the prostate, distinction of adenocarcinoma of the lung from squamous cell carcinoma and epithelioid mesothelioma, and identification of basal-type features in urothelial cancer are solely driven by CK5. At least for the purpose of distinguishing thoracic tumors, monospecific CK5 antibodies may be better suited than bispecific CK5/6 antibodies.

AB - Cytokeratins (CKs) 5 and 6 are functionally unrelated but often analyzed together using bispecific antibodies in diagnostic immunohistochemistry. To better understand the diagnostic utility of CK5 or CK6 alone, tissue microarrays with > 15,000 samples from 120 different tumor types as well as 608 samples of 76 different normal tissues were analyzed by immunohistochemistry. In normal tissues, both CKs occurred in the squamous epithelium; CK5 dominated in basal and CK6 in suprabasal layers. CK5 (not CK6) stained basal cells in various other organs. Within tumors, both CK5 and CK6 were seen in > 95% of squamous cell carcinomas, but other tumor entities showed different results: CK5 predominated in urothelial carcinoma and mesothelioma, but CK6 in adenocarcinomas. Joint analysis of both CK5 and CK6 obscured the discrimination of epithelioid mesothelioma (100% positive for CK5 alone and for CK5/6) from adenocarcinoma of the lung (12.8% positive for CK5 alone; 23.7% positive for CK5/6). CK5 and CK6 expressions were both linked to high grade, estrogen receptor, and progesterone receptor negativity in breast cancer (p < 0.0001 each), grade/stage progression in urothelial cancer (p < 0.0001), and RAS mutations in colorectal cancer (p < 0.01). Useful diagnostic properties which are commonly attributed to CK5/6 antibodies such as basal cell staining in the prostate, distinction of adenocarcinoma of the lung from squamous cell carcinoma and epithelioid mesothelioma, and identification of basal-type features in urothelial cancer are solely driven by CK5. At least for the purpose of distinguishing thoracic tumors, monospecific CK5 antibodies may be better suited than bispecific CK5/6 antibodies.

U2 - 10.1007/s00428-021-03204-4

DO - 10.1007/s00428-021-03204-4

M3 - SCORING: Journal article

C2 - 34559291

VL - 480

SP - 433

EP - 447

JO - VIRCHOWS ARCH

JF - VIRCHOWS ARCH

SN - 0945-6317

IS - 2

ER -