A systematic analysis of commonly used antibodies in cancer diagnostics

Gremel, Gabriela; Bergman, Julia; Djureinovic, Dijana; Edqvist, Per‐Henrik; Vikas, Maindad; Bharambe, Bhavana M; Khan, Wasif Ali Z. A.; Navani, Sanjay; Elebro, Jacob; Jirström, Karin; Hellberg, Dan; Uhlén, Mathias; Micke, Patrick; Pontén, Fredrik

doi:10.1111/his.12255

Cited by 14 publications

(12 citation statements)

References 29 publications

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“…Because papillary configuration of glands can also be seen in papillary thyroid carcinoma and is known to produce a miliary pattern on chest radiography, immunohistochemical staining was required to distinguish between the two 15. Ultimately, the cells stained positive for napsin A, which has a 87–94% sensitivity for lung adenocarcinoma, and were negative for thyroglobulin, which carries a 95% sensitivity and specificity for papillary thyroid carcinoma 16 17. TTF-1 is highly expressed in lung adenocarcinomas and small cell carcinomas (75–90% sensitivity) with positive staining ruling out metastatic adenocarcinomas of the breast, colon, kidney and stomach 18…”

Section: Discussionmentioning

confidence: 99%

Maintaining sharp focus on a grainy film: miliary pattern in an elderly woman with acute respiratory failure

Hensley

Hilal²,

Neltner

et al. 2015

BMJ Case Reports

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An elderly woman with a history of pulmonary tuberculosis reportedly diagnosed and treated 30 years prior to presentation was found unresponsive at home. Chest imaging revealed innumerable pulmonary nodules worrisome for an infectious process, specifically tuberculosis. The patient deteriorated rapidly and in accordance with her wishes, aggressive interventions were withheld. She died within 48 h from respiratory failure. A limited chest autopsy was performed and revealed the cause of death as lymphangitic spread of cancer from a primary lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Maintaining sharp focus on a grainy film: miliary pattern in an elderly woman with acute respiratory failure

Hensley

Hilal²,

Neltner

et al. 2015

BMJ Case Reports

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“…In addition, three independent TMA cohorts were used. Cohort 1 was a multi-cancer cohort including 940 tumor samples, representing 22 different tumor sites (Additional file 2: Table S2, [13]). Formalin-fixed, paraffin-embedded (FFPE) tumor specimens were identified from the archives of Uppsala University Hospital, Falun Hospital and Lund University Hospital, where all cases were originally diagnosed between 1984 and 2011.…”

Section: Methodsmentioning

confidence: 99%

“…All human tissue samples used in cohort 1 were anonymized in accordance with approval and advisory report from the Uppsala Ethical Review Board (2007–159), and consequently the need for informed consent was waived by the ethics committee. The use and analyses based on tissues in cohort 1 has previously been described [13]. …”

Section: Acknowledgementsmentioning

confidence: 99%

A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

et al. 2017

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BackgroundThere is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC).MethodsHuman Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival.ResultsCUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203–0.719, P = 0.003).ConclusionsCUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3030-6) contains supplementary material, which is available to authorized users.

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“…A biomarker intended to be used for labelling of beta cells in pancreas may only require absent staining in other cells of islet of Langerhans and abdominal organs adjacent to pancreas, while unspecific antibody binding in other tissues does not interfere with the result (Lindskog et al., 2012). In contrast, a potential diagnostic marker with the aim to accurately determine the origin of a metastasis tumour needs a higher level of specificity, in order to set the correct diagnosis (Gremel et al., 2014). The strategies also differ between validation of antibodies in high‐throughput projects and antibodies intended to be used in biomarker assays.…”

Section: Ideal Work‐flowmentioning

confidence: 99%

“…aim to accurately determine the origin of a metastasis tumour needs a higher level of specificity, in order to set the correct diagnosis (Gremel et al, 2014). The strategies also differ between validation of antibodies in high-throughput projects and antibodies intended to be used in biomarker assays.…”

Section: Ideal Work-flowmentioning

confidence: 99%

Garbage in, garbage out: A critical evaluation of strategies used for validation of immunohistochemical biomarkers

et al. 2014

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The use of immunohistochemistry (IHC) in clinical cohorts is of paramount importance in determining the utility of a biomarker in clinical practice. A major bottleneck in translating a biomarker from bench‐to‐bedside is the lack of well characterized, specific antibodies suitable for IHC. Despite the widespread use of IHC as a biomarker validation tool, no universally accepted standardization guidelines have been developed to determine the applicability of particular antibodies for IHC prior to its use. In this review, we discuss the technical challenges faced by the use of immunohistochemical biomarkers and rigorously explore classical and emerging antibody validation technologies. Based on our review of these technologies, we provide strict criteria for the pragmatic validation of antibodies for use in immunohistochemical assays.

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A systematic analysis of commonly used antibodies in cancer diagnostics

Cited by 14 publications

References 29 publications

Maintaining sharp focus on a grainy film: miliary pattern in an elderly woman with acute respiratory failure

Maintaining sharp focus on a grainy film: miliary pattern in an elderly woman with acute respiratory failure

A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Garbage in, garbage out: A critical evaluation of strategies used for validation of immunohistochemical biomarkers

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