Anti‑EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash

Carneiro, Fabiana Pirani; Muniz‐Junqueira, Maria Imaculada; Carneiro, Marcos de Vasconcelos; Oliveira, Ísis de Araújo; Soares, A.J.M.; Haar, Nathália de Vargas; Takano, Gustavo Henrique Soares; Vianna, Leonora Maciel de Sousa; Caldas, Guilherme de Carvalho; Vieira, Danillo Leal Marinho; Frutuoso, Lígia Lins; Brito, Larissa Matos Rodrigues; Siqueira, Rafael Vieira Martins de; Parente, Amanda Moreira; Castro, Tércia Maria Mendes Lousa de; Peres, Isabela; Mendes, Lianna Martha Soares; Borges, Tatiana Karla dos Santos; Ferreira, Vânia Maria Moraes; Motoyama, Akira

doi:10.3892/ol.2019.10468

Cited by 11 publications

(15 citation statements)

References 27 publications

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“…EMT, and taking into account that carcinomatous cells can lose EpCAM expression due to this process (Hyun et al, 2016), it is possible to explain why some malignant effusions with positive conventional cytology (May-Grünwald-Giemsa staining) and/or PAP-cytology/IHC have negative FC results. It has been suggested that using EpCAM antibodies against different epitopes of the molecule would increase the chance of its detection in metastatic carcinoma effusions (Carneiro et al, 2019). In addition, some poorly differentiated epithelial tumors downregulate the expression of EpCAM (Pillai et al, 2013), potentially leading to contradictory data between FC and cytology.…”

Section: T a B L Ementioning

confidence: 99%

The utility of flow cytometry in the diagnostic work up of malignant effusions due to nonhematopoietic neoplasms

Wong-Arteta

Rey

Aragón

et al. 2020

Cytometry Part B Clinical

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Malignant pleural effusion and peritoneal carcinomatosis are frequent causes of effusion. Cytological evaluation (PAP-stained slides followed by immunocytochemistry, IHC, if applicable) is currently the gold standard for the diagnosis of malignant effusions, but its sensitivity varies between 40 and 80%, being a time-consuming technique. Although flow cytometry (FC) is not routinely used in the diagnosis or follow-up of nonhematopoietic neoplasms, it has the advantage of being rapidly applicable to fresh samples, potentially decreasing the time for the diagnosis. The main objective of this study was to assess the utility of FC as a confirmatory tool in the diagnosis of neoplastic effusions, based on the expression of EpCAM antibody in tumor cells versus the cytological evaluation. In this work 1,535 serous fluids were collected, of which 101 (68 pleural, 33 ascites) were selected through a screening algorithm and sent to the FC and cytological evaluation. Seventy-three of these samples (46 pleural, 27 ascites) were considered malignant as determined by clinical, cytological and radiological criteria. According to our data, 75% (55/73) of these samples were positive by Cytology/IHC and 74% (54/73) by FC. We noticed that, although the sensitivity, specificity, and area under the curve were similar, the turnaround time was shorter when using FC. Moreover, these results clearly improved by combining both techniques. We conclude that FC provides information about malignant effusions faster than immunohistochemical staining, and we believe that performing both techniques in parallel would improve diagnostic performance.

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Section: T a B L Ementioning

confidence: 99%

The utility of flow cytometry in the diagnostic work up of malignant effusions due to nonhematopoietic neoplasms

Wong-Arteta

Rey

Aragón

et al. 2020

Cytometry Part B Clinical

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“…Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is involved in cell adhesion, signaling, migration, proliferation and differentiation [ 21 , 22 ]. More than 90% of metastatic lesions of malignant ovarian tumors, as well as many other carcinomas, overexpress EpCAM relative to normal epithelial cells and normal mesothelium [ 21 , 23 , 24 , 25 ]. Furthermore, EpCAM expression in tumor cells is not confined to the basolateral side as in normal cells, making cancer cells better accessible to EpCAM-targeting agents via the apical side [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

EpCAM-Binding DARPins for Targeted Photodynamic Therapy of Ovarian Cancer

Brand

Lith

Jong

et al. 2020

Cancers

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Ovarian cancer is the most lethal gynecological malignancy due to late detection associated with dissemination throughout the abdominal cavity. Targeted photodynamic therapy (tPDT) aimed at epithelial cell adhesion molecule (EpCAM), overexpressed in over 90% of ovarian cancer metastatic lesions, is a promising novel therapeutic modality. Here, we tested the specificity and activity of conjugates of EpCAM-directed designed ankyrin repeat proteins (DARPins) with the photosensitizer IRDye 700DX in in vitro and in vivo ovarian cancer models. EpCAM-binding DARPins (Ec1: Kd = 68 pM; Ac2: Kd = 130 nM) and a control DARPin were site-specifically functionalized with fluorophores or IRDye 700DX. Conjugation of anti-EpCAM DARPins with fluorophores maintained EpCAM-specific binding in cell lines and patient-derived ovarian cancer explants. Penetration of DARPin Ec1 into tumor spheroids was slower than that of Ac2, indicative of a binding site barrier effect for Ec1. DARPin-IRDye 700DX conjugates killed EpCAM-expressing cells in a highly specific and illumination-dependent fashion in 2D and 3D cultures. Furthermore, they effectively homed to EpCAM-expressing subcutaneous OV90 xenografts in mice. In conclusion, the high activity and specificity observed in preclinical ovarian cancer models, combined with a high specificity in patient material, warrant a further investigation of EpCAM-targeted PDT for ovarian cancer.

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“…The immunoreactivity of anti-p16 antibody was evaluated and compared with the expression of claudin-4 and MOC-31 by using total immunostaining score (TIS), which is the product of the proportion score and the intensity score. This score has been previously used to evaluate the expression of p16 and EpCAM in histological specimens [9,14,15]. Here, this score was applied to enable comparison between p16 expression with those of MOC-31 (anti-EpCAM clone) and claudin-4.…”

Section: Discussionmentioning

confidence: 99%

“…All samples were freshly prepared and no fixatives or preservative solutions were used. Cell block preparation and immunocytochemistry was performed as previously described [14], using the plasma-thromboplastin method. In brief, samples were centrifuged and 100 μl of plasma and 100 μl of thromboplastin (Stago®, Asnières sur Seine, France) were added onto the cell pellet.…”

Section: Methodsmentioning

confidence: 99%

P16 as a marker of carcinoma in effusions and peritoneal washing

Carneiro¹,

Amorim²,

Carneiro³

et al. 2020

BMC Cancer

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Background: Considering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/ thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68. Results: P16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%.Conclusion: Overexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.

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Anti‑EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash

Cited by 11 publications

References 27 publications

The utility of flow cytometry in the diagnostic work up of malignant effusions due to nonhematopoietic neoplasms

The utility of flow cytometry in the diagnostic work up of malignant effusions due to nonhematopoietic neoplasms

EpCAM-Binding DARPins for Targeted Photodynamic Therapy of Ovarian Cancer

P16 as a marker of carcinoma in effusions and peritoneal washing

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