Use of cytokeratins 7 and 20 in determining the origin of metastatic carcinoma of unknown primary, with special emphasis on lung cancer

Rubin, Brian P.; Skarin, Arthur T.; Pisick, Evan; Rizk, Majida; Salgia, Ravi

doi:10.1097/00008469-200102000-00009

Cited by 89 publications

(60 citation statements)

References 24 publications

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“…The various cytokeratin subtypes are expressed in a tissue-specific manner on cells of epithelial origin. Adenocarcinomas of the lung have been reported to be CK7+, while colon cancers are positive for CK20 staining (Wang et al, 1995;Rubin et al, 2001). Carcinoembryonic antigen (CEA) expression can also be used to evaluate colon adenocarcinoma lesions (Lagendijk et al, 1998(Lagendijk et al, , 1999.…”

Section: Discussionmentioning

confidence: 99%

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

et al. 2002

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The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We reviewed a total of 102 tissue samples from patients in our tumour registry, with either primary or metastatic lung or colorectal adenocarcinoma. Tissue sections were stained for cytokeratin 7 and 20 and read as positive or negative for staining. Clinical and radiologic information was reviewed from computerised charts. The cytokeratin 7+/cytokeratin 207 pattern characterised 96% (29 out of 30) of primary and 95% (21 out of 22) of metastatic lung adenocarcinomas. All the primary (26), and 88% (21 out of 24) of metastatic colorectal adenocarcinomas stained cytokeratin 77/cytokeratin 20+. Samples from a variety of metastatic sites were evaluated for cytokeratin 7 and 20 staining. Out of the 102 samples, in 95% (97 out of 102) of the cases, the cytokeratin 7 and cytokeratin 20 staining pattern characterised and differentiated between lung and colorectal adenocarcinoma. Primary and metastatic lung adenocarcinomas show a cytokeratin 7+/cytokeratin 207 staining pattern, while colorectal adenocarcinomas stain cytokeratin 77/cytokeratin 20+. Cytokeratin staining is helpful in the diagnostic differentiation of metastatic lesions from these two common primaries, and assists in determining the site of origin of metastatic lesions.

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Section: Discussionmentioning

confidence: 99%

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

et al. 2002

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“…All 1420 colorectal cancer and 57 normal colonic mucosa samples were immunostained for CK20 (clone Ks20. 8 2 O, sections for immunostaining were subjected to heat antigen retrieval in a microwave oven (1200 W, 15 min) in 0.001 mol/l ethylenediaminetetraacetic acid, pH 8.0 for MLH1 and MSH2, pH 9 for CK20 and CK7 and in 0.01 mol/l citrate buffer, pH 6.0 for MSH6 and pH 2 for CDX2. Endogenous peroxidase activity was blocked using 0.5% H 2 O 2 .…”

Section: Immunohistochemistry Of Tissue Microarraymentioning

confidence: 99%

“…Particularly, the primary site of a metastatic carcinoma can be very difficult to determine by morphology alone. [1][2][3][4] Immunohistochemical markers are a well established tool in daily diagnostic practice and help to define tumor lineage when antibodies are applied against specific tumor antigens. 5 In particular, the differential expression profile of various cytokeratin (CK) types by tumors at different primary locations can be essential in determining the origin of a malignant tumor.…”

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confidence: 99%

“…5 In particular, the differential expression profile of various cytokeratin (CK) types by tumors at different primary locations can be essential in determining the origin of a malignant tumor. 1,2,4,[6][7][8] CKs are intermediate filament proteins and 20 subtypes have been classified based on isoelectric pH (focusing) and molecular weight. 5,[9][10][11] Two of the most used stains are CK20 and CK7.…”

mentioning

confidence: 99%

“…5,10,12,13 CK20 is normally expressed in the gastrointestinal epithelium, Merkel cells and urothelium 14,15 whereas CK7 can be detected in normal tissue and tumors of the lung, breast, ovary, biliary tract and endometrium. 2,5 According to several studies the multi-marker phenotype CK20 þ /CK7À is observed in colorectal cancer in approximately 75-95% 2,14 of cases whereas the multimarker phenotype CK20À/CK7 þ favors primary tumors of the lung, breast, biliary tract, pancreas, ovary and endometrium. 5 However, the combined use of CK20 and CK7 is limited, especially in the distinction of primary and secondary mucinous tumors in the ovary 16 thereby making the addition of other markers mandatory.…”

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confidence: 99%

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Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status

et al. 2008

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The differentiation of colorectal cancer from primary tumors at other sites can be challenging. Often a panel of immunohistochemical protein markers is needed to distinguish between these entities. Protein expression differs significantly in colorectal cancer depending on mismatch repair status and is also heterogeneous among mismatch repair-proficient or -deficient tumors. The aim of this study was to systematically analyze the diagnostic and prognostic role of the commonly used multi-marker phenotype CK20/CK7/CDX2 on a large series of colorectal cancers stratified by mismatch repair status. The immunohistochemical analysis of CK20, CK7 and CDX2 was performed on 1197 mismatch repair-proficient and 223 mismatch repair-deficient colorectal cancers using a tissue microarray. Multi-marker combinations of CK20/CK7/CDX2 were explored. Univariate and multivariable analysis of the markers was evaluated for their association with several clinico-pathological end points namely T stage, N stage, tumor grade, vascular invasion, intratumoral lymphocytes and survival. Multimarker phenotypes with CK20 and CDX2 negativity were more frequently found in mismatch repair-deficient than in mismatch repair-proficient colorectal cancer (19.3 vs 7.5% and 21.6 vs 6.7%, respectively; Po0.001). In both colorectal cancer subsets loss of CK20 was associated with higher tumor grade (Po0.001) and with presence of intratumoral lymphocytes (Po0.001 and P ¼ 0.02, respectively). In the proficient mismatch repair subset CK20 overexpression was an independent adverse prognostic factor (P ¼ 0.041) and CDX2 underexpression was linked to tumor progression. Loss of CDX2 and CK20 is more frequently encountered in mismatch repair-deficient colorectal cancer, which should be taken into consideration to differentiate between primary and metastatic colorectal cancer in daily practice. Although associated with lower tumor grade, CK20 overexpression is an independent adverse prognostic factor in mismatch repair-proficient colorectal cancer.

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The development of the human vaginal fornix and the portio cervicis

et al. 2021

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Introduction One of the transitional zones of the human body is situated in the cervix uteri. The developmental differentiation of epithelial and stromal characteristics in such a region is of high clinical interest. However, few studies have focused on the development of this region, and information in anatomical and clinical textbooks is limited. We therefore examined the development of the human vaginal fornix and the cervix uteri during prenatal development. Materials and Methods We examined 29 female embryos and fetuses between 20 and 34 weeks and two newborns using histology and immunohistochemistry. Results The characteristic shape of the portiocervicis and the vaginal fornix first became visible in mid‐term fetuses because of the different muscular coats and of an uncategorized Müllerian‐derived epithelium, which was rapidly replaced by a multilayered squamous epithelium. Only thereafter, in older fetuses, were there organogenetic differentiation of the epithelia and the underlying stroma of the cervical canal. UGS‐derived p63/CK17‐positive cells could be identified as precursor cells for the squamous epithelium, and Müllerian‐derived CK7‐positive cells for the columnar‐type epithelium. Both cell types and different stromal zones were already present in a prenatal transformation zone. Initial functional differentiation could be observed in perinatal stages. Conclusions Our results on prenatal human development strongly support the view that two different cell lineages meet at the transitional zone of the cervix uteri and that these lineages depend on alternative signals from the underlying stromal compartment.

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Use of cytokeratins 7 and 20 in determining the origin of metastatic carcinoma of unknown primary, with special emphasis on lung cancer

Cited by 89 publications

References 24 publications

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status

The development of the human vaginal fornix and the portio cervicis

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