Next generation immunohistochemistry: Emerging substitutes to genetic testing?

Andrici, Juliana; Gill, Anthony J.; Hornick, Jason L.

doi:10.1053/j.semdp.2017.05.004

Cited by 35 publications

(30 citation statements)

References 109 publications

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“…Immunohistochemistry for SDHB and SDHA has obtained an important place in diagnostic pathology for the recognition of any SDH-related tumor and has become a well-established surrogate marker for molecular analysis and for confirmation of genetic variants of unknown significance. The current challenges are as follows: (1) to elaborate on such immunohistochemical markers in other areas of pathology [79]; (2) to detect genetic abnormalities in related genetic sequences (promoter regions, intron/exon boundaries) or genes (SDH assembly factors, other citric acid cycle genes); (3) to use the increasing knowledge on the functional consequences of loss of enzymatic activity for the development of therapeutic interventions that may affect or prevent tumor development.…”

Section: Discussionmentioning

confidence: 99%

The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes

2018

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Succinate dehydrogenase (SDH) is an enzyme complex, composed of four protein subunits, that plays a role in both the citric acid cycle and the electron transport chain. The genes for SDHA, SDHB, SDHC, and SDHD are located in the nuclear DNA, and mutations in these genes have initially been described in paragangliomas (PGL) and pheochromocytomas (PCC), which are relatively rare tumors derived from the autonomic nervous system and the adrenal medulla, respectively. Patients with SDH mutations, that are almost exclusively in the germline, are frequently affected by multiple PGL and/or PCC. In addition, other tumors have been associated with SDH mutations as well, including gastrointestinal stromal tumors, SDH-deficient renal cell carcinoma, and pituitary adenomas. Immunohistochemistry for SDHB and SDHA has been shown to be a valuable additional tool in the histopathological analysis of these tumors, and can be considered as a surrogate marker for molecular analysis. In addition, SDHB immunohistochemistry is relevant in the decision-making whether a genetic sequence variant represents a pathogenic mutation or not. In this review, we highlight the current knowledge of the physiologic and pathologic role of the SDH enzyme complex and its involvement in endocrine and non-endocrine tumors, with an emphasis on the applicability of immunohistochemistry.

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Section: Discussionmentioning

confidence: 99%

The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes

2018

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“…Although SDH‐deficient RCCs are much less aggressive than FH‐deficient RCCs, metastatic progression has been reported in approximately 10% to 20% of cases, which is likely greater than that reported in oncocytic tumors, such as chromophobe RCC. Prospective recognition of these tumors, whether by clinical correlation or use of SDHB immunostaining, also is important for evaluating the risk of paragangliomas, which tend to be aggressive when arising in this syndrome …”

Section: Distinctive Rcc Types With Strong Hereditary Associationsmentioning

confidence: 99%

New entities, new technologies, new findings: A review of the cytologic features of recently established subtypes of renal cell carcinoma

Robila

Kraft

Smith

2019

Cancer Cytopathology

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Several new renal tumor types with distinctive pathologic, epidemiologic, and genetic signatures have recently been adopted in the fourth edition of the World Health Organization classification. In succeeding years, the cytologic features of most of these new types have been described, adding to the trend of increasing diagnostic accuracy for most common renal cell carcinoma subtypes and the important diagnostic role of cytologic sampling in the management and personalization of therapy. The current article reviews the cytologic findings from these recently established renal cell carcinoma subtypes. Emphasis is placed on cytologic diagnostic clues, confirmatory ancillary testing, salient differential diagnoses, and challenges that can be encountered in an attempt to render accurate interpretations in small samples.

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“…Triage of these cases, as anticipated by the above referenced commentary on “FH‐deficient” immunophenotype, has been aided by the recent advent of immunohistochemical surrogates of FH mutation status (Fig. ).…”

Section: Fh‐deficient Rcc − From Metabolomic Derangement To Aggressivmentioning

confidence: 99%

“…63 This provisional term, for use in morphologically appropriate high grade tumors where clinical and genetic correlation are unavailable but FH-deficient phenotype confirmed by IHC (or mutations in the tumor), is to be employed with strong recommendation for genetic testing, given that most such cases are still believed to be syndromal. 58 Triage of these cases, as anticipated by the above referenced commentary on "FH-deficient" immunophenotype, has been aided by the recent advent of immunohistochemical surrogates of FH mutation status 13 (Fig. 2).…”

Section: Fh-deficient Rcc à From Metabolomic Derangement To Aggressivmentioning

confidence: 99%

High grade infiltrative adenocarcinomas of renal cell origin: New insights into classification, morphology, and molecular pathogenesis

Singh

Ohe

Smith

2018

Pathology International

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Collecting duct carcinoma was described over 30 years ago as a renal tumor, based in the medullary collecting system, with tubulopapillary morphology, prominent infiltrative growth, and stromal desmoplasia. While diagnostic workup has always emphasized exclusion of upper tract urothelial carcinoma and metastatic adenocarcinoma to the kidney, the molecular era of renal cell carcinoma classification has enabled recognition of and provided tools for diagnosis of new entities in this morphologic differential. In this review, we consider these developments, with emphasis on renal medullary carcinoma, closely related renal cell carcinoma, unclassified with medullary phenotype, and fumarate hydratase-deficient renal cell carcinoma. Integration of ancillary studies with suggestive patterns of morphology is emphasized for practical implementation in contemporary diagnosis, and several emerging tumor types in the morphologic differential are presented.

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Next generation immunohistochemistry: Emerging substitutes to genetic testing?

Cited by 35 publications

References 109 publications

The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes

The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes

New entities, new technologies, new findings: A review of the cytologic features of recently established subtypes of renal cell carcinoma

High grade infiltrative adenocarcinomas of renal cell origin: New insights into classification, morphology, and molecular pathogenesis

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