Endocr Pathol (2015) 26:211–217 DOI 10.1007/s12022-015-9374-7
BRAF Immunohistochemistry Using Clone VE1 is Strongly Concordant with BRAFV600E Mutation Test in Papillary Thyroid Carcinoma Jung-Soo Pyo 1 & Jin Hee Sohn 1 & Guhyun Kang 2
Published online: 10 May 2015 # Springer Science+Business Media New York 2015
Abstract The aim of this study was to investigate the concordance between BRAFV600E mutation test and immunohistochemistry (IHC) and determine the diagnostic accuracy of IHC for papillary thyroid carcinoma (PTC) through a systematic review, meta-analysis, and diagnostic test accuracy review. The current systematic review and meta-analysis included 1141 PTCs in 11 eligible studies. We investigated the concordance rate and performed subgroup analysis using tissue and cytologic samples. Diagnostic test accuracy review was conducted and calculated using the value of area under curve (AUC) on the summary receiver operating characteristic (SROC) curve. The positive rate of BRAF IHC was 79.1 % (903 of 1141 cases), and the BRAFV600E mutation was found in 76.6 % (874 of 1141 cases). The concordance rates were 0.921 (95 % confidence interval (CI) 0.877–0.950) and 0.894 (95 % CI 0.801–0.946) in IHC positive and negative subgroups, respectively. In the diagnostic test accuracy review, the pooled sensitivity and specificity were 0.97 (95 % CI 0.95–0.98) and 0.78 (95 % CI 0.72–0.83). The value of AUC on SROC curve was 0.983, and diagnostic odds ratio was 164.28 (95 % CI 57.69–467.80). Our results showed that BRAF IHC was strongly concordant with BRAF mutation test and had high diagnostic accuracy in BRAF mutation analysis of PTC.
* Jin Hee Sohn [email protected] 1
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 78 Saemunan-gil, Jongno-gu, Seoul 110-746, South Korea
2
Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, South Korea
Keywords Papillary thyroid carcinoma . BRAFV600E mutation . Immunohistochemistry . Concordance . Meta-analysis
Introduction Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, accounting for at least 80– 90 % of thyroid cancers [1]. In PTC, genetic alterations, such as B-type Raf kinase (BRAF) mutation, RET/PTC translocation, and Ras mutations, have been reported [2]. BRAFV600E mutation is the most common genetic alteration and is detected in up to 90 % of PTCs [1, 3–5]. The protein kinase BRAF is a component of the RAS/RAF/MEK/ERK signaling pathway [6] and regulates cell fate in response to extracellular signals in a number of human cancers [1]. The BRAFV600E mutation is important in maintaining and promoting thyroid cancer progression [7]. Although the correlation between BRAFV600E mutation and poor clinicopathological features is controversial [6, 8–10], the BRAFV600E mutation may be useful in the diagnosis and prediction of behavior in PTC. In daily clinical practice, several tests for BRAF mutation have been introduced and most methods are DNA sequencing or molecular tests based on PCR, such as direct sequencing, pyrosequencing, allele-specific polymerase chain reaction (PCR), peptide nucleic acid (PNA)-mediated clamping PCR, and real-time PCR. These methods are expensive, multi-step, and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation was introduced, and the mouse antihuman BRAFV600E monoclonal antibody (clone VE1) has been used for research purposes. The correlation between BRAF IHC and the mutation test has been reported; however, the diagnostic accuracy of BRAF IHC has yet to be fully elucidated.
212
Although IHC is a useful and verified diagnostic clinical tool, whether BRAF IHC can replace PCR-based BRAF mutation tests is not clear. In the present study, we performed a concordant analysis between BRAF IHC and mutation test through a systematic review and meta-analysis in PTC. Moreover, diagnostic test accuracy review was conducted to elucidate the diagnostic accuracy of BRAF IHC for BRAF mutation in PTC.
Materials and Methods
Endocr Pathol (2015) 26:211–217
assessment of publication bias, Begg’s funnel plot and Egger’s test were performed. If significant publication bias was found, the fail-safe N and trim-fill tests were additionally conducted to confirm the degree of publication bias. The results were two-sided and considered statistically significant when P
BRAF Immunohistochemistry Using Clone VE1 is Strongly Concordant with BRAFV600E Mutation Test in Papillary Thyroid Carcinoma Jung-Soo Pyo 1 & Jin Hee Sohn 1 & Guhyun Kang 2
Published online: 10 May 2015 # Springer Science+Business Media New York 2015
Abstract The aim of this study was to investigate the concordance between BRAFV600E mutation test and immunohistochemistry (IHC) and determine the diagnostic accuracy of IHC for papillary thyroid carcinoma (PTC) through a systematic review, meta-analysis, and diagnostic test accuracy review. The current systematic review and meta-analysis included 1141 PTCs in 11 eligible studies. We investigated the concordance rate and performed subgroup analysis using tissue and cytologic samples. Diagnostic test accuracy review was conducted and calculated using the value of area under curve (AUC) on the summary receiver operating characteristic (SROC) curve. The positive rate of BRAF IHC was 79.1 % (903 of 1141 cases), and the BRAFV600E mutation was found in 76.6 % (874 of 1141 cases). The concordance rates were 0.921 (95 % confidence interval (CI) 0.877–0.950) and 0.894 (95 % CI 0.801–0.946) in IHC positive and negative subgroups, respectively. In the diagnostic test accuracy review, the pooled sensitivity and specificity were 0.97 (95 % CI 0.95–0.98) and 0.78 (95 % CI 0.72–0.83). The value of AUC on SROC curve was 0.983, and diagnostic odds ratio was 164.28 (95 % CI 57.69–467.80). Our results showed that BRAF IHC was strongly concordant with BRAF mutation test and had high diagnostic accuracy in BRAF mutation analysis of PTC.
* Jin Hee Sohn [email protected] 1
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 78 Saemunan-gil, Jongno-gu, Seoul 110-746, South Korea
2
Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, South Korea
Keywords Papillary thyroid carcinoma . BRAFV600E mutation . Immunohistochemistry . Concordance . Meta-analysis
Introduction Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, accounting for at least 80– 90 % of thyroid cancers [1]. In PTC, genetic alterations, such as B-type Raf kinase (BRAF) mutation, RET/PTC translocation, and Ras mutations, have been reported [2]. BRAFV600E mutation is the most common genetic alteration and is detected in up to 90 % of PTCs [1, 3–5]. The protein kinase BRAF is a component of the RAS/RAF/MEK/ERK signaling pathway [6] and regulates cell fate in response to extracellular signals in a number of human cancers [1]. The BRAFV600E mutation is important in maintaining and promoting thyroid cancer progression [7]. Although the correlation between BRAFV600E mutation and poor clinicopathological features is controversial [6, 8–10], the BRAFV600E mutation may be useful in the diagnosis and prediction of behavior in PTC. In daily clinical practice, several tests for BRAF mutation have been introduced and most methods are DNA sequencing or molecular tests based on PCR, such as direct sequencing, pyrosequencing, allele-specific polymerase chain reaction (PCR), peptide nucleic acid (PNA)-mediated clamping PCR, and real-time PCR. These methods are expensive, multi-step, and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation was introduced, and the mouse antihuman BRAFV600E monoclonal antibody (clone VE1) has been used for research purposes. The correlation between BRAF IHC and the mutation test has been reported; however, the diagnostic accuracy of BRAF IHC has yet to be fully elucidated.
212
Although IHC is a useful and verified diagnostic clinical tool, whether BRAF IHC can replace PCR-based BRAF mutation tests is not clear. In the present study, we performed a concordant analysis between BRAF IHC and mutation test through a systematic review and meta-analysis in PTC. Moreover, diagnostic test accuracy review was conducted to elucidate the diagnostic accuracy of BRAF IHC for BRAF mutation in PTC.
Materials and Methods
Endocr Pathol (2015) 26:211–217
assessment of publication bias, Begg’s funnel plot and Egger’s test were performed. If significant publication bias was found, the fail-safe N and trim-fill tests were additionally conducted to confirm the degree of publication bias. The results were two-sided and considered statistically significant when P
