Diagnostic Usefulness of Claudin-3 and Claudin-4 for Immunocytochemical Differentiation between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks

Kim, Nah Ihm; Kim, Ga-Eon; Lee, Ji Shin

doi:10.1159/000447008

Cited by 10 publications

(15 citation statements)

References 27 publications

(88 reference statements)

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“…Lonardi et al also described intra‐cytoplasmic dot staining in mesothelial and inflammatory cells, which they considered non‐specific, while Jo et al reported weak cytoplasmic staining in some mesotheliomas. By contrast, others have described membranous staining with Claudin‐4 in around a quarter of cases of reactive mesothelium. We found the pattern of cytoplasmic staining observed in mesothelial cells easy to discriminate from the linear membrane staining observed in the majority of adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 84%

“…There is less concordance in published results for the expression of claudin‐4 by mesothelial cells. Some authors have found no reactivity in mesothelial cells, whereas Kim et al reported weak membranous staining in 27.5% of reactive mesothelial cases. Soini et al also reported reactivity in a series of surgical specimens including 24 adenocarcinomas (100% positive) and 35 mesotheliomas (23%).…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies have found similarly high sensitivity of claudin‐4 for adenocarcinomas from a range of sites. Studies by Jo et al, Lonardi et al and Kim et al, evaluated the use of claudin‐4 in cytology effusion specimens and reported its sensitivity to be 100%, 99% and 99.1%, respectively. Studies based on surgical specimens have also confirmed claudin‐4 is expressed by a high proportion of cases in a wide variety of epithelial tumours .…”

Section: Discussionmentioning

confidence: 99%

“…1 Several studies have suggested that claudin-4 IHC may be useful in differentiating metastatic carcinoma from mesothelioma and reactive mesothelial cells in serous effusion specimens. [2][3][4] However, the reactivity of claudin-4 with mesothelial cells remains unclear, with some studies reporting staining in up to 28% of reactive 5 and malignant 6 mesothelial cases.…”

Section: Introductionmentioning

confidence: 99%

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Claudin‐4 immunohistochemistry is a useful pan‐carcinoma marker for serous effusion specimens

et al. 2019

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Objective To evaluate the utility of claudin‐4 as a pan‐carcinoma marker in cell‐blocks of effusion specimens and compare results with Ber‐Ep4 staining. Methods Effusion cell‐blocks (n = 284) were stained for claudin‐4 and results compared with Ber‐Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas. Results All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin‐4. Claudin‐4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin‐4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin‐4 outperformed Ber‐Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin‐4 compared with Ber‐Ep4, respectively. Only two cases were claudin‐4−/Ber‐Ep4+. Significantly (P < .0064) more cases of metastatic adenocarcinoma stained positive for claudin‐4 (131/137; 95.6%) than Ber‐Ep4 (117/137; 86.2%). Claudin‐4 staining was present in 15/20 (75%) of neuroendocrine carcinomas, 3/4 (75%) squamous cell carcinoma and 3/3 (100%) urothelial cell carcinoma. All eight cases of melanoma were negative for both claudin‐4 and Ber‐Ep4. Conclusions Claudin‐4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber‐Ep4.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Claudin‐4 immunohistochemistry is a useful pan‐carcinoma marker for serous effusion specimens

et al. 2019

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“…The markers used to identify malignant epithelial cells were MOC-31, Claudin 4 and IMP3, but several other adenocarcinomas markers have been used to distinguish malignant epithelial cells from mesothelial cells such as B72.3, CEA and Ber-EP4 (30)(31)(32)(33)(34). Besides, some primary site markers of adenocarcinoma can also contribute to distinction between mesothelial and epithelial malignant cells such as estrogen receptor, progesterone receptor, GATA3, mammoglobin, GCPd15 for breast; Napsin-A and TTF-1 for lung; CdX-2, villin, SATB2 for gastrointestinal tract; PSA for prostate; PAX8, HBME and estrogen receptor for ovary; Cd10 and PAX 8 for kidney; hepatocyte-specific antigen for liver.…”

Section: Discussionmentioning

confidence: 99%

A panel of markers for identification of malignant and non-malignant cells in culture from effusions

et al. 2017

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The aim of the present study was to identify cell types in primary culture from malignant and non-malignant effusions. Effusion samples were subjected to cytology and culture. Immunocytochemistry was performed in cytological slides to evaluate malignancy (positivity for malignancy markers) and in culture slides for identification of cell types in growth. A total of 143 effusion samples (pleural n=76; peritoneal n=37; pericardial n=4; and peritoneal lavage n=26) were analyzed. Cell growth was observed in 34.9% of all samples and immunocytochemistry for identification of cell types in culture slides was conclusive in 90% of them. In non-malignant samples (n=28), growth of mesothelial cells, macrophages and of both cell types was identified in 82.14, 10.71 and 7.14%, respectively. In malignant samples (n=17, all carcinomas), growth of malignant epithelial cells and of both malignant epithelial and mesothelial cells was identified in 41.17 and 23.52%, respectively. In the remaining 35.29% of malignant samples, the only cells in growth were mesothelial and/or macrophages instead of malignant epithelial cells. In conclusion, in culture of malignant effusions, mesothelial cells may be simultaneously identified with malignant epithelial cells. Besides, mesothelial cells and macrophages may be the only cells identified in malignant effusion culture. Therefore, a broad panel of cell markers should be used for unmistakable identification of cells in studies of effusion primary culture. The ideal malignant effusion sample to obtain culture of neoplastic cells should be that without the presence of mesothelial cells and macrophages.

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The utility of claudin‐4 versus MOC‐31 and Ber‐EP4 in the diagnosis of metastatic carcinoma in cytology specimens

Najjar

Gan

Stewart

et al. 2022

Cancer Cytopathology

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Background Claudin‐4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin‐4 versus MOC‐31 and Ber‐EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens. Methods This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine‐needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin‐4 and compared with those previously stained for MOC‐31 and Ber‐EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases). Results None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin‐4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC‐31 and Ber‐EP4, claudin‐4 had the highest specificity and PPV (100% for each), followed by Ber‐EP4. Claudin‐4 showed high sensitivity (93.7%), albeit lower than MOC‐31. MOC‐31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber‐EP4 had the lowest sensitivity (91.6%). Conclusions Claudin‐4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC‐31 and Ber‐EP4. Mesothelial lineage can be ruled out when claudin‐4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin‐4 and Ber‐EP4 results in the highest combined sensitivity and specificity.

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Diagnostic Usefulness of Claudin-3 and Claudin-4 for Immunocytochemical Differentiation between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks

Cited by 10 publications

References 27 publications

Claudin‐4 immunohistochemistry is a useful pan‐carcinoma marker for serous effusion specimens

Claudin‐4 immunohistochemistry is a useful pan‐carcinoma marker for serous effusion specimens

A panel of markers for identification of malignant and non-malignant cells in culture from effusions

The utility of claudin‐4 versus MOC‐31 and Ber‐EP4 in the diagnosis of metastatic carcinoma in cytology specimens

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