Diagnostic Value of Claudin-4 and EZH2 Immunohistochemistry in Effusion Cytology

Elhosainy, Aliaa; Hafez, Momen; Yassin, Etemad; Adam, Mohamed A.; Elnaggar, Maha; Aboulhagag, Noha

doi:10.31557/apjcp.2022.23.8.2779

Cited by 3 publications

(3 citation statements)

References 34 publications

(62 reference statements)

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“…It is a highly useful marker for distinguishing reactive mesothelial cells and metastatic adenocarcinoma. Several previous studies have analysed the sensitivity and specificity of claudin‐4 in the evaluation of effusion cytology (Table 3) with most studies highlighting the 100% sensitivity for adenocarcinomas irrespective of primary site as was observed in the present study as well 4,6,7,11–15 . However, there are some discrepancies with regards to the specificity.…”

Section: Discussionsupporting

confidence: 48%

“…with most studies highlighting the 100% sensitivity for adenocarcinomas irrespective of primary site as was observed in the present study as well. 4,6,7,[11][12][13][14][15] However, there are some discrepancies with regards to the specificity. Although the clone 3EC21 has been used in all the studies, some studies have reported lower specificity of 70%-77%.…”

Section: Discussionmentioning

confidence: 99%

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Claudin‐4 immunocytochemistry is specific and sensitive for the diagnosis of malignant carcinomatous effusions: Results from a pilot study

Hruaii,

Thirunavukkarasu,

Prabha

et al. 2023

Diagnostic Cytopathology

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BackgroundClaudin‐4, a tight junction associated protein expressed in epithelial cells, is purported as a highly specific and sensitive marker for epithelial malignancies. Our aim was to assess the sensitivity, specificity and real‐time utility of claudin‐4 immunocytochemistry (ICC) in the diagnostic work‐up of suspected malignant effusions.MethodsClaudin‐4 (3E2C1 clone) ICC was performed prospectively in effusion cell blocks where other ICC markers were being performed as part of reporting over 3 months. Based on claudin‐4 staining in unequivocal malignant and reactive effusions, the sensitivity and specificity was calculated. In cases signed out as inconclusive encompassing atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) and negative for malignancy, change in diagnostic category based on addition of claudin‐4 ICC was assessed.ResultsStudy included 107 effusions. Claudin‐4 stained 100% of metastatic adenocarcinomas including those with primaries in lung, breast, ovary, female genital tract, gastrointestinal tract and pancreatic‐biliary tract, and was negative in all reactive mesothelial and mesothelioma effusions with sensitivity of 100% (48/48) and specificity of 95% (20/21) for adenocarcinoma. Claudin‐4 upgraded the diagnostic category to positive in 70% (16/23) of SFM, 20% (1/5) of AUS, and in 50% (5/10) of negative effusions. Among cases with confirmed serosal involvement status on follow‐up, claudin‐4 showed sensitivity, specificity, positive predictive value and negative predictive values of 85% (11/13), 100% (3/3), 100% (10/10) and 75% (3/4), respectively, for metastatic adenocarcinoma.ConclusionClaudin‐4 as a single marker is sensitive and specific for adenocarcinoma and is a valuable addition to the ICC armamentarium.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Claudin‐4 immunocytochemistry is specific and sensitive for the diagnosis of malignant carcinomatous effusions: Results from a pilot study

Hruaii,

Thirunavukkarasu,

Prabha

et al. 2023

Diagnostic Cytopathology

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“…Overall, the sensitivity, specificity, positive predictive, and negative predictive values for CLDN4 in metastatic adenocarcinoma were 85%, 100%, 100%, and 75%, respectively [158]. Similar results were noted by Elhosainy et al, where CLDN4 exhibited 95.8% sensitivity and 96.9% specificity in the detection of metastatic adenocarcinoma [159].…”

Section: Tumor Markerssupporting

confidence: 81%

Claudins in Cancer: A Current and Future Therapeutic Target

Hana,

Thaw Dar,

Galo Venegas

et al. 2024

IJMS

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Claudins are a family of 27 proteins that have an important role in the formation of tight junctions. They also have an important function in ion exchange, cell mobility, and the epithelial-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evidence shows improved outcomes when combining monoclonal antibodies against claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently, chimeric antigen receptor T-cells targeting claudin 18 are under investigation. In this review, we will discuss the major functions of claudins, their distribution in the normal as well as cancerous tissues, and their effect in cancer metastasis, with a special focus on the therapeutic targeting of claudins to improve cancer outcomes.

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An Updated Contextual Approach to Mesothelial Proliferations in Pleural Effusion Cytology Leveraging Morphology, Ancillary Studies, and Novel Biomarkers

Miller,

Holmes,

Lew

2023

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids. Objective.— To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions as well as relevant clinicoradiologic contexts and ancillary tests. Data Sources.— Existing scientific and clinical literature as of January 2023. Conclusions.— We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.

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Diagnostic Value of Claudin-4 and EZH2 Immunohistochemistry in Effusion Cytology

Cited by 3 publications

References 34 publications

Claudin‐4 immunocytochemistry is specific and sensitive for the diagnosis of malignant carcinomatous effusions: Results from a pilot study

Claudin‐4 immunocytochemistry is specific and sensitive for the diagnosis of malignant carcinomatous effusions: Results from a pilot study

Claudins in Cancer: A Current and Future Therapeutic Target

An Updated Contextual Approach to Mesothelial Proliferations in Pleural Effusion Cytology Leveraging Morphology, Ancillary Studies, and Novel Biomarkers

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