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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.

Asunto(s)

Carcinoma , Mesotelioma , Humanos , Claudina-4 , Estudios Retrospectivos , Carcinoma/diagnóstico , Epitelio/patología , Mesotelioma/diagnóstico , Mesotelioma/patología , Biomarcadores de Tumor , Diagnóstico Diferencial

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INTRODUCTION: Body cavity effusions are routinely used as cytologic specimens. The distinction between metastatic carcinoma, mesothelioma, and reactive mesothelial cells remains a major challenge. Immunohistochemistry (IHC) is a supplemental method that can aid in diagnosis and often involves many markers as part of an IHC panel. Several immunohistochemical markers are now widely used. This study aims to determine the optimal immunomarkers and IHC panels to differentiate reactive mesothelial cells from metastatic cancer in body cavity fluid samples. METHODS: IHC was performed for claudin-4, MOC-31, Ber-Ep4, D2-40, and calretinin on sections derived from 152 cellblocks containing effusions. The samples consisted of 16 (10.53%) benign and 136 (89.47%) malignant tumors, including 87 (63.97%) lung cancers, nine (6.62%) breast cancers, 11 (8.09%) gynecologic cancers, seven (5.15%) pancreaticobiliary cancers, and 22 (16.17%) unspecified primary malignancies. RESULTS: Claudin-4, MOC-31, Ber-EP4, D2-40, and calretinin demonstrated sensitivities of 91.18%, 91.91%, 55.88%, 90.44%, and 98.53%, respectively. The corresponding specificities were 100.00%, 100.00%, 100.00%, 93.75%, and 100.00%. The sensitivity and specificity were both 100% when claudin-4 or MOC-31 was combined with calretinin. The combination of four markers as an IHC panel (claudin-4, MOC-31, calretinin, and D2-40) had a sensitivity of 97.79% and a specificity of 100.00%. CONCLUSION: Claudin-4 and MOC-31 both demonstrated significant diagnostic value in distinguishing metastatic epithelial carcinoma from reactive mesothelium. The sensitivity, specificity, and accuracy of these two markers, one of which is an epithelial marker and one of which is a mesothelial marker, reached 100%. Therefore, a combination of these two markers may be appropriate.

Asunto(s)

Adenocarcinoma , Mesotelioma , Humanos , Femenino , Calbindina 2 , Adenocarcinoma/patología , Claudina-4 , Epitelio/patología , Inmunohistoquímica , Mesotelioma/diagnóstico , Mesotelioma/patología , Sensibilidad y Especificidad , Biomarcadores de Tumor , Diagnóstico Diferencial

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Background: Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, hasdiverse roles in these tissues, including in cell adhesion, proliferation, differentiation, cell cycle regu-lation, migration and intracellular signaling. It is also over-expressed in most malignant neoplasia, partic-ipating in theinitiation, progression, and metastatic dissemination of the tumor. The expression and roles of this protein in oralneoplasia, particularly in odontogenic tumors, remain unestablished. The objective of this study consisted in analyzing the expression of this protein in ameloblastoma and tooth germ.Material and Methods: Ep-CAM (MOC-31) expression was evaluated by immunohistochemistry in tooth germs(TG) (n = 16) ameloblastomas (AM) (n = 60) and 2 ameloblastic carcinomas. Sections were visualized in theirtotality with an optical microscope, and positivity observed in cell membrane and cytoplasm was graded according to the following semi-quantitative scale: Neg, "essentially unstained", for negative sections or staining <5% ofcells; + for staining of 5-50% of cells; ++ for staining >50% of cells.Results: Most tooth germs expressed MOC-31 (81.3%), strong staining was observed both in the inner epitheliumof the enamel organ and in the adjacent stellate reticulum. 16.7% of the AM cases showed MOC-31 expression,the immunoexpression expression was diffuse at the cytoplasmic and membrane level. The only two cases ofameloblastic carcinoma included were strong positive to MOC-31. No correlation was observed between proteinexpression and gender, age, clinical variants, or histological subtypes.Conclusions: Overexpression was found in TG and ameloblastic carcinoma compared to AM; further studies withdifferent experimental strategies are suggested to clarify the biological significance of this finding. (AU)

Asunto(s)

Humanos , Ameloblastoma/patología , Carcinoma/metabolismo , Carcinoma/patología , Molécula de Adhesión Celular Epitelial/metabolismo , Tumores Odontogénicos/patología , Germen Dentario/metabolismo

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INTRODUCTION: Due to a relatively high recurrence rate of facial basal cell carcinoma (BCC), its morbidity is very significant. AIM: To analyse the expression of α-SMA, E-cadherin, Ber-Ep4 and MOC-31 as predictors of local recurrence in a group of patients with primary and recurrent BCCs of the face in correlation with histological and clinical data. MATERIAL AND METHODS: The study cohort included 79 patients with facial BCC (52 with primary BCC and 27 with recurrent BCC) who were treated at the Department of Cranio-Maxillofacial Surgery of the Jagiellonian University, Krakow in 1997-2009. RESULTS: Significant risk factors for local recurrence included: recurrent tumour (p = 0.001), multifocal BCC (p = 0.01), incomplete tumour excision (p = 0.02) and the aggressive infiltrating histologic subtype of BCC (p = 0.05). In the group of primary BCCs, positive expression of stromal α-SMA (p = 0.03) correlated with a statistically significant higher recurrence rate and so did positive expression of α-SMA in tumour cells of recurrent BCC (p = 0.002). In the group of primary aggressive BCC subtypes, reduced expression of MOC-31 was also associated with a higher rate of relapse (p = 0.02). CONCLUSIONS: Our findings provide information about α-SMA and MOC-31 expression in primary and recurrent BCCs. These data may contribute to the formulation of a more targeted treatment plan and follow-up strategy for patients with facial basal cell carcinoma.

RESUMEN

BACKGROUND: The diagnosis of atypical cases in the effusion cytology sample often poses a challenge to the cytologists. AIMS AND OBJECTIVES: We evaluated the diagnostic role of MOC31 in the metastatic adenocarcinoma in effusion fluid. MATERIALS AND METHODS: The cytological examination and MOC31 immunostaining in the cell block sections were carried out in 64 cases of serous effusion. A total of 23 cases showed atypical cytology, out of which suspicious for malignancy (SFM) and atypia of undetermined significance (AUS) were 19 and 4 cases, respectively. In these cases, we also performed calretinin immunostaining. The cytological features, results of MOC31 immunostaining, and follow-up data were correlated to find out the sensitivity and specificity of MOC31 immunostaining in the diagnosis of metastatic adenocarcinoma. RESULT: The sensitivity and specificity of MOC31 were 100%. MOC31 detected all the cases of metastatic adenocarcinoma. MOC31 showed strong positivity in 19 cases of SFM. All these cases had a malignant outcome in histopathology or follow-up data. In AUS cases, MOC31 immunostaining was negative with a benign outcome. In all the atypical but malignant cases calretinin stain showed diffuse cytoplasmic and nuclear positivity. In contrast, MOC31 showed strong membranous positivity and occasionally cytoplasmic positivity. CONCLUSION: MOC31 is an excellent marker of metastatic adenocarcinoma in the serous effusion. The membranous positivity of MOC31 and negative calretinin immuno-staining are helpful in atypical cytological cases to avoid the diagnostic dilemma. The MOC31 positivity is significantly useful in discrete atypical cells which are more challenging to recognize.

Asunto(s)

Adenocarcinoma/inmunología , Anticuerpos Monoclonales , Líquido Ascítico/inmunología , Biomarcadores de Tumor/análisis , Molécula de Adhesión Celular Epitelial/análisis , Inmunohistoquímica , Derrame Pericárdico/inmunología , Derrame Pleural/inmunología , Adenocarcinoma/secundario , Adulto , Anciano , Líquido Ascítico/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pericárdico/patología , Derrame Pleural/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos

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BACKGROUND: The ImmunoPeCa trial investigated the use of intraperitoneal MOC31PE immunotoxin as a novel therapeutic principle for the treatment of peritoneal metastasis from colorectal cancer (PM-CRC). We here report long-term outcome from the trial. METHODS: This was a dose-finding trial aiming to evaluate safety and toxicity (primary endpoint) upon a single dose of intraperitoneal MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with mitomycin C. Overall survival (OS) and disease-free survival (DFS) were secondary endpoints. Twenty-one patients received the study drug at four dose levels on the first postoperative day, including six patients constituting an expansion cohort. RESULTS: With a 34-month follow-up, the median OS was not reached and the estimated 3-year OS was 78%. Median DFS for all patients was 21 months and the 3-year DFS was 33%, with a median follow-up of 31 months. When excluding patients with potential favorable characteristics from the analysis (n = 4), the median DFS was 13 months and the 3-year OS 72%. CONCLUSIONS: The promising long-term outcome combined with low systemic absorbance, high drug concentration and cytotoxic activity in peritoneal fluid support further investigations of clinical efficacy.

Asunto(s)

Neoplasias Colorrectales/patología , Inmunoconjugados/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Adulto , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Persona de Mediana Edad , Mitomicina/uso terapéutico , Noruega , Neoplasias Peritoneales/cirugía

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OBJECTIVE: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) originate from the same cell origin, that is, the intercalated cells of the collecting duct.[1] In most cases, there are clear morphologic differences between RO and ChRCC; however, in some instances, overlapping features may be encountered and the differentiation between the two entities becomes difficult.[2] Several immunohistochemical markers with different expression patterns in ChRCC and RO have been described to rule out this dilemma. MATERIALS AND METHODS: About 47 primary renal neoplasms that had been diagnosed as RO or ChRCC were submitted for immunohistochemical staining of amylase α-1A (AMY1A), MOC 31, and CD 82. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy have been analyzed. RESULTS: AMY1A positivity was observed in all RO cases in our work with 91.7% sensitivity and 100% specificity in the diagnosis of RO. The PPV of its expression was (100%) and NPV (97.2%) with a diagnostic accuracy of 97.9%. A significant high expression of MOC 31 was observed in ChRCC compared to its expression in RO with a statistical significance (P < 0.001). In addition, we obtained 82.9% sensitivity and 91.7% specificity of MOC 31 expression in the diagnosis of ChRCC. The positive predictive value (PPV) was (96.7%), negative predictive value (NPV) (64.7%) with diagnostic accuracy (85.1%). In our studied cases, we detected positive immunoexpression of CD 82 in 10 cases (83.3%) of ChRCC. However, it was lost in all RO cases (100%). CD 82 sensitivity and specificity in differentiating ChRCC from RO were 100% and 83.3%, respectively. CONCLUSION: We propose MOC 31 and CD 82 as negative immunostains for RO, as these markers are commonly expressed in ChRCC. In conjunction with AMY1A strong immunopositivity in RO cases, we provide a triple panel of biomarkers (AMY1A, MOC 31, and CD 82) for the distinction between RO and ChRCC.

Asunto(s)

Adenoma Oxifílico/diagnóstico , Carcinoma de Células Renales/diagnóstico , Proteína Kangai-1/genética , Neoplasias Renales/diagnóstico , Glicoproteínas de Membrana/genética , alfa-Amilasas Salivales/genética , Adenoma Oxifílico/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

The distinction of malignant mesothelioma from non-small-cell lung carcinoma (NSCLC) usually requires immunohistochemistry, but some broad-spectrum carcinoma markers stain mesotheliomas, and it remains unclear which broad-spectrum markers are most valuable for distinguishing these malignancies. Here, we directly compared the sensitivity and specificity of three broad-spectrum carcinoma markers, claudin-4, Ber-EP4, and MOC-31, for distinguishing NSCLC from mesothelioma. Immunohistochemistry was performed on tissue microarrays containing 68 epithelioid mesotheliomas, 31 sarcomatoid mesotheliomas, and 147 non-small-cell lung cancers (53 adenocarcinomas, 60 squamous cell carcinomas, 13 large-cell carcinomas, and 21 sarcomatoid carcinomas). For adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma, claudin-4 staining was present in 103 of 126 cases (82%), MOC-31 staining was present in 112 of 126 cases (89%), and Ber-EP4 staining was present in 113 of 126 cases (90%); these values were not statistically different. Claudin-4 stained 0 of 68 (0%), MOC-31 stained 22 of 68 (32%), and Ber-EP4 stained 24 of 68 (35%) epithelioid mesotheliomas; thus, the specificities for NSCLC versus epithelioid mesothelioma were 100%, 68%, and 65%, respectively. Claudin-4 staining was present in 7 of 21 (33%), MOC-31 staining was present in 8 of 21 (38%), and Ber-EP4 staining was present in 5 of 21 (24%) sarcomatoid carcinomas. All three markers were negative in 12 of 21 (57%) sarcomatoid carcinomas. Sarcomatoid mesotheliomas were not stained with any of these markers. We conclude that claudin-4 has considerably greater specificity and comparable sensitivity to MOC-31 and Ber-EP4 for distinguishing NSCLC from epithelioid malignant mesothelioma. The use of all three markers may be necessary for sarcomatoid neoplasms, given their limited sensitivity.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/química , Claudina-4/análisis , Molécula de Adhesión Celular Epitelial/análisis , Neoplasias Pulmonares/química , Mesotelioma/química , Carcinoma de Pulmón de Células no Pequeñas/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Mesotelioma/patología , Valor Predictivo de las Pruebas , Análisis de Matrices Tisulares

RESUMEN

BACKGROUND: Early detection of small HCC and differentiation between HCC from AC metastatic to the liver is very essential for surgical pathologists, due to different treatment modalities. Immunohistochemistry plays a very important role in such conditions. In our study, we aimed to identify the diagnostic benefits of Arginase-1, FTCD& MOC-31 in the early detection of HCC in normal or cirrhotic liver, differentiation between HCC and metastatic ACs to the liver, and for early detection of small micro-metastases from ACs to liver. MATERIALS AND METHODS: We included 20 samples from liver cirrhosis, 10 samples from normal liver tissue, 30 samples from primary HCCs in the liver, and 30 samples from metastatic ACs to the liver. We have evaluated Arginase-1, FTCD, and MOC-31 expression using immunohistochemistry. RESULTS: The sensitivity of Arginase-1 expression in differentiation between HCC and metastatic carcinoma was 93.3% and the specificity was 93.3%. The sensitivity of FTCD expression in differentiation between HCC and normal or cirrhotic liver and early detection of well-differentiated HCC was 90% and the specificity was 86.7%. The sensitivity of MOC-31 expression in differentiation between HCC and metastatic carcinoma was 90% and the specificity was 90%. The sensitivity of combination of panel of Arginase 1 + FTCD + MOC 31 expression in differentiation between HCC, metastatic carcinoma, and normal and cirrhotic liver was 93.3% and the specificity was 93.3%. CONCLUSIONS: The combination of Arginase 1 + FTCD + MOC 31 expression was helpful in diagnosing most cases of HCC and metastatic carcinoma with high sensitivity and specificity.

Asunto(s)

Adenocarcinoma/metabolismo , Anticuerpos Monoclonales/biosíntesis , Arginasa/biosíntesis , Carcinoma Hepatocelular/metabolismo , Diferenciación Celular/fisiología , Neoplasias Hepáticas/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Anciano , Anticuerpos Monoclonales/metabolismo , Arginasa/metabolismo , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Diagnóstico Diferencial , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia

RESUMEN

OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) is a protein expressed on surfaces of healthy epithelia, and is overexpressed in dysplasias and carcinomas. Immunohistochemistry (IHC) utilizing antibodies that react with EpCAM, such as MOC-31 and Ber-EP4, distinguish reactive mesothelial cells from carcinomas in serous effusions. IHC is crucial in effusions with singly dispersed atypical cells, a scenario with a broad differential, including hematopoietic malignancies. Plasma cell neoplasms (PCN) are the second most common hematopoietic malignancy, manifesting as multiple myeloma or plasmacytoma, with 6% of cases developing serous cavity involvement. Most PCNs are readily recognizable; however, variants that deviate from the classic cytomorphology risk erroneous diagnosis. This study demonstrates EpCAM expression in a subset of PCNs, highlighting a potential diagnostic pitfall in serous effusion cytology. METHODS: A 10-year retrospective search for cytology specimens with a diagnosis of PCN was performed. All cases demonstrating CD138/CD38 and monoclonal immunoglobulin expression, and adequately cellular cell block were included. IHC analysis for MOC-31 and Ber-EP4 was performed using Ventana Benchmark Ultra. Scoring was performed as follows: total IHC score equals the positive proportion (0 = no positive tumor cells; 1 = <1%; 2 = 1-10%; 3 =11-33%; 4 = 34-66%; 5 = 67-100%) plus staining intensity (0, no staining; 1, weak; 2, moderate; 3, strong). A score > 4 was considered positive. RESULTS: 2 of 28 (7%) PCNs demonstrated positivity for MOC-31 and Ber-Ep4. CONCLUSION: A subset of PCNs in cytology samples show positivity for MOC-31 and Ber-EP4 which could result in misinterpretation as carcinoma.

Asunto(s)

Especificidad de Anticuerpos/inmunología , Citodiagnóstico , Molécula de Adhesión Celular Epitelial/inmunología , Plasmacitoma/diagnóstico , Plasmacitoma/inmunología , Anciano , Femenino , Humanos , Masculino , Plasmacitoma/patología

RESUMEN

INTRODUCTION: Although cytological examination helps in diagnosis of malignancy in serous effusion, at times it is difficult to differentiate atypical reactive mesothelial cells from adenocarcinoma (AC) cells. To resolve this problem, various ancillary methods have been used. Immunocytochemistry (ICC) is one such commonly used technique in which various panel of antibodies has been tried. Unfortunately, so far no unique marker is available to solve this issue. Hence, the present study evaluates the efficacy of four antibody panel comprising of MOC-31, epithelial membrane antigen (EMA), calretinin (CAL), and mesothelin (MES) to solve this problem. MATERIALS AND METHODS: Forty-two cases suspected of malignant effusion in pleural/peritoneal fluid and 42 cases of reactive effusion were included. Cytospin smears were prepared and stained with Giemsa stain for cytomorphological diagnosis. Cytospin smears and cell blocks were made forICC. ICC for MOC-31, EMA, CAL, and MES was performed. RESULTS: Among the suspected malignant effusion cases, 30 cases were AC and 12 cases were suspicious for malignancy by cytomorphology. MOC31 demonstrated 100% sensitivity (Sn) and 95.24% specificity (Sp), and EMA had 88.1% Sn and 92.86% Sp for AC cases. CAL demonstrated 100% and 97.62%, and MES 97.62% and 88.1% Sn and Sp in reactive mesothelial cells, respectively. CONCLUSION: In conclusion, combination of MOC-31 and CAL as a limited panel will be helpful in giving an appropriate diagnosis in difficult cases and thereby, help in patient management. In addition, ICC on cytospin smears gave results similar to cell blocks, and if standardised cytospin is simple technique to perform, unlike cell blocks.

RESUMEN

In effusion cytology, a clear distinction between reactive mesothelial cells and metastatic adenocarcinoma cells is sometimes challenging mainly due to similarities in the cytomorphological features. In such cases for definitive diagnosis, paraffin-embedded cell block examination and immunohistochemistry are helpful in making this distinction. MOC-31 is one of the proposed immunomarker for adenocarcinoma cells. We undertook to evaluate the role of MOC-31 as a marker for identifying adenocarcinoma cells in effusion specimen. A total of 185 paraffin-embedded cell blocks of effusion samples were identified, of these 111 cases were of metastatic adenocarcinoma. MOC-31 was positive in 101 of the 111 cases of metastatic adenocarcinoma. Minimal focal cytoplasmic staining was also seen in 7 of the 74 cases of reactive mesothelial cells, but these were taken negative as they did not show membrane positivity. The sensitivity and specificity of MOC-31 for metastatic adenocarcinoma cells were 92.5%, and 100% respectively, positive and negative predictive value (NPV) was 100% and 91.14%, respectively. MOC-31 can be used as a reliable marker in effusions for distinguishing metastatic adenocarcinoma from reactive mesothelial cases.

Asunto(s)

Adenocarcinoma/diagnóstico , Anticuerpos Monoclonales/inmunología , Biomarcadores de Tumor/inmunología , Diagnóstico Diferencial , Inmunohistoquímica/métodos , Adenocarcinoma/inmunología , Adenocarcinoma/fisiopatología , Líquidos Corporales , Citodiagnóstico/métodos , Exudados y Transudados , Femenino , Humanos , Mesotelioma/diagnóstico , Sensibilidad y Especificidad

RESUMEN

Peritoneal metastasis (PM) is an important feature of epithelial ovarian cancer (EOC) and is a frequent site of drug resistant disease recurrence, identifying PM-EOC an important clinical challenge. The MOC31PE immunotoxin targets and kills tumor cells expressing the epithelial cell adhesion molecule (EpCAM), which is highly expressed in EOC, and MOC31PE is being investigated for use in treatment of PM-EOC. The efficacy of MOC31PE treatment alone and in combination with cytotoxic drugs was investigated in two human EpCAM expressing EOC cell lines, B76 and MDHA-2774, in vitro and in corresponding mouse models mimicking PM-EOC. MOC31PE efficaciously killed tumor cells alone and showed equal or superior activity in vitro (paclitaxel, cisplatin, carboplatin) and in vivo (paclitaxel, mitomycin C) compared to the investigated cytotoxic drugs. Additive, or importantly, no antagonistic effects were observed in combination experiments. In ex vivo cell culture, the cytotoxic effect of MOC31PE was studied on freshly isolated surgical EOC samples. All investigated fresh EOC samples expressed EpCAM and MOC31PE effectively reduced cell viability in ex vivo cultures. In conclusion, these results, together with our previous preclinical and clinical experience, support development of MOC31PE for treatment of PM-EOC in combination with currently used cytotoxic drugs.

RESUMEN

BACKGROUND: All malignant tumors may spread throughout the pleural, peritoneal, and pericardial cavities. The presence of tumor cells in serosal fluid is a poor prognostic indicator. It may be difficult to differentiate nuclear atypia of mesothelial cells due to injury of serosal surfaces from mesothelioma or malignant epithelial tumor cells. Epithelial and mesothelial immunohistochemical markers can be used in such conditions. The aim of this study was to evaluate the expression of two immunohistochemical markers (MOC-31 and EZH2) in serosal effusions. METHODS: The study included a total of 142 patients diagnosed with benign or malignant cytology between January 2012 and April 2014. MOC-31 and EZH2 were applied to the cell blocks of 53 patients with benign cytology and 89 patients with malignant cytology determined based on the clinical, radiological data, histopathology diagnosis, and clinical follow-up in the absence of any surgical material of the patient in the hospital archive system. RESULTS: None of the benign cases showed MOC-31 and EZH2 expression, although these markers were positive in 96 and 93% respectively of the malignant cases. CONCLUSION: In conclusion, it could be considered cost-effective to use a double immunohistochemical antibody kit for these two markers, MOC-31 membranous and EZH2 nuclear staining, in the diagnosis of malignant effusions. Diagn. Cytopathol. 2017;45:118-124. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Anticuerpos Monoclonales/metabolismo , Líquido Ascítico/patología , Biomarcadores de Tumor/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Derrame Pleural Maligno/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/genética , Biomarcadores de Tumor/genética , Niño , Diagnóstico Diferencial , Proteína Potenciadora del Homólogo Zeste 2/genética , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND: Recently, claudin-4 (CL4) immunocytochemistry was reported to be useful for differential diagnosis in effusion cytology. We wondered whether CL4 might be useful for "single-shot" identification of metastatic carcinoma. The purpose of this study was to evaluate the usefulness of CL4 in effusion cytology. METHODS: In total, 266 cases (169 metastatic carcinomas, eight malignant mesotheliomas, and 89 reactive mesothelial cells) were selected. Immunocytochemical examinations of cell-block sections were performed for CL4, Ber-EP4, and MOC-31. We used an arbitrary 4-tiered scale based on both staining intensity and positive-cell percentage among all target cells, and calculated a staining index score (sum of the above two scores). RESULTS: In a ROC-curve analysis, higher area-under-curve values were found for CL4 than for Ber-EP4 or MOC-31 (0.982, 0.942, and 0.926, respectively). CONCLUSIONS: Since CL4 exhibited similar or superior usefulness to Ber-EP4 and MOC-31, it could become the first choice for the above differential diagnosis in effusion cytology. Diagn. Cytopathol. 2016;44:499-504. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Anticuerpos Monoclonales/inmunología , Líquido Ascítico/patología , Carcinoma/patología , Claudina-4/inmunología , Mesotelioma/patología , Derrame Pleural Maligno/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/inmunología , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad

RESUMEN

Typical cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are morphologically dissimilar. It is well known, however, that poorly differentiated SCC may assume a basaloid phenotype, complicating the histologic distinction between these 2 neoplasms. Selected immunohistochemical stains have been used in the past to aid in that differential diagnosis. In the current study, additional markers were evaluated to determine whether they would be helpful in that regard. Twenty-nine cases of metatypical (squamoid) BCC (MBCC) and 25 examples of basaloid SCC (BSCC) were studied using the antibodies Ber-EP4 and MOC-31 as well as a plant lectin preparation from Ulex europaeus I (UEA-1). The resulting immunostains were interpreted independently by 3 pathologists, and the results showed that MBCCs demonstrated strong and diffuse staining for Ber-EP4 (25/29) and MOC-31 (29/29). In contrast, BSCCs tended to be only sporadically reactive for both markers (4/25 and 1/25 cases, respectively). Labeling for UEA-1 was observed in almost all BSCCs (24/25), but only 6 of 29 cases of MBCC showed limited, focal staining with that lectin. These data suggest that MOC-31 is a useful marker in the specified differential diagnosis, especially when used together with UEA-1.

Asunto(s)

Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Cutáneas/metabolismo , Anticuerpos Monoclonales/química , Biomarcadores de Tumor/química , Biomarcadores de Tumor/metabolismo , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica/métodos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Ulex/química

RESUMEN

BACKGROUND: The cytologic assessment of pleural effusions to distinguish carcinoma cells from reactive mesothelial cells is particularly challenging. The aim of this study was to investigate the diagnostic value of monoclonal antibody (MOC-31) and calretinin in pleural fluid of patients with lung cancer to significantly improve the diagnostic accuracy. METHODS: The expressions of MOC-31 and calretinin were detected by means of S-P immunocytochemical technique in pleural effusions of patients with lung cancer (n = 92) and in patients with benign lung disease (n = 70). RESULTS: The positive rate of MOC-31 in pleural fluid was 90.2% (83/92) from patients with lung cancer and 2.9% (2/70) from patients with benign lung diseases, showing a significant difference (P < 0.01). Calretinin was expressed 87.1% (61/70) in benign lung diseases and 6.5% (6/92) in lung cancer, also showing a significant difference (P < 0.01). The optimal combination for assay was MOC-31 + calretinin: Sensitivity and specificity were 100 and 98.6%, respectively. CONCLUSION: MOC-31 and calretinin are of important clinical value for diagnosing and differentially diagnosing the cancer cells in pleural fluid of patients with lung cancer.

Asunto(s)

Adenocarcinoma/diagnóstico , Anticuerpos Monoclonales/genética , Biomarcadores de Tumor/genética , Calbindina 2/genética , Neoplasias Pulmonares/diagnóstico , Derrame Pleural Maligno/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/metabolismo , Biomarcadores de Tumor/metabolismo , Calbindina 2/metabolismo , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Cavidad Pleural/metabolismo , Cavidad Pleural/patología , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patología , Sensibilidad y Especificidad

RESUMEN

Cytoreductive surgery and intraperitoneal (i.p.) chemotherapy constitute a curative treatment option in mucinous peritoneal surface malignancies of intestinal origin, but treatment outcome is highly variable and the search for novel therapies is warranted. Immunotoxins are attractive candidates for targeted therapy in the peritoneal cavity because of direct cytotoxicity, distinct mechanisms of action and tumor cell selectivity. The MOC31PE immunotoxin targets the tumor-associated adhesion protein EpCAM (Epithelial Cell Adhesion Molecule), and has been administered safely in early clinical trials. In our work, the efficacy of i.p. administration of MOC31PE alone and together with mitomycin C (MMC) was investigated in unique animal models of human mucinous peritoneal surface malignancies. In initial model validation experiments, clear differences in efficacy were demonstrated between MMC and oxaliplatin, favoring MMC in five investigated tumor models. Subsequently, MOC31PE and MMC were given as single i.p. injections alone and in combination. In the PMCA-2 model, moderate growth inhibition was obtained with both drugs, while the combination resulted in at least additive effects; whereas the PMP-2 model was highly sensitive to both drugs separately and in combination and intermediate sensitivity was found for the PMCA-3 model. Furthermore, results from ex vivo experiments on freshly obtained mucinous tumor tissue from animals and patients suggested that classic mechanisms of immunotoxin activity were involved, i.e., inhibition of protein synthesis and induction of apoptosis. The present results suggest that adding MOC31PE to MMC-based i.p. chemotherapy should be further explored for EpCAM-expressing peritoneal surface malignancies, and a phase I trial is in preparation.

Asunto(s)

ADP Ribosa Transferasas/uso terapéutico , Antígenos de Neoplasias/inmunología , Toxinas Bacterianas/uso terapéutico , Moléculas de Adhesión Celular/inmunología , Exotoxinas/uso terapéutico , Inmunotoxinas/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Factores de Virulencia/uso terapéutico , Animales , Modelos Animales de Enfermedad , Molécula de Adhesión Celular Epitelial , Femenino , Ratones , Ratones Endogámicos BALB C , Mitomicina/uso terapéutico , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Neoplasias Peritoneales/patología , Exotoxina A de Pseudomonas aeruginosa

RESUMEN

We studied the feasibility of immunocytochemistry (ICC), in situ hybridization (ISH), and polymerase chain reaction (PCR) after Cellient(™) automated cell block processing, and tested whether methanol-based PreservCyt(™) fixation could replace formalin fixation, in an attempt to eliminate toxic formaldehyde vapors. Immunostaining with 30 different antibodies was performed on cell blocks from 73 FNA specimens and 42 body cavity fluid specimens prepared by Cellient(™) automated processing that uses the methanol-based fixative (PreservCyt(™) ). For each antibody we evaluated ICC in at least three different cell block specimens and compared it with immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) histological sections from the corresponding tumors. The quality of DNA and RNA in Cellient(™) blocks was analyzed by ISH, applying a SYT gene break-apart assay and EBER probes, respectively. Moreover, DNA quality was analyzed by PCR by using primer sets for DNA products of 100, 200, 300, 400, 500, and 600 base pairs, and evaluated by gel electrophoresis. When compared with IHC results in corresponding FFPE tumor tissue from the same patient, 24 out of 30 antibodies showed concordant ICC results. With FISH, distinctive hybridization signals were observed for SYT DNA sequences and EB virus RNA sequences. With PCR, DNA products, up to 600 base pairs in size, were readily observed after gel electrophoresis. The antibodies that showed concordant immunostaining in Cellient(™) blocks could be applied to diagnostic algorithms that proved to be helpful in the discrimination of major tumor types (carcinoma, lymphoma, melanoma, and germ cell tumors), discrimination of carcinoma subtypes, and determination of primary tumor site in cases of metastatic carcinoma. In a separate study, we found that the application of ICC to this cell block technique provided additional diagnostic and clinically important information in 24% of 100 consecutive cases. The high quality of DNA and RNA in Cellient(™) cell blocks allowed sensitive and specific molecular biologic analysis, in particular FISH and PCR.

Asunto(s)

Fijadores/química , Metanol/química , Neoplasias/patología , Citodiagnóstico , Estudios de Factibilidad , Formaldehído/química , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Técnicas de Diagnóstico Molecular , Neoplasias/diagnóstico , Adhesión en Parafina , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Fijación del Tejido/métodos

RESUMEN

PURPOSE: Renal tumors consist of heterogeneous groups that frequently show complex and overlapping morphology, thus making it difficult to make a correct diagnosis. One of the most problematic differential diagnoses is to distinguish chromophobe renal cell carcinoma (RCC) from oncocytoma. These should be distinguished by differences in their behavior and clinical outcome. Our study was performed to identify whether caveolin-1 and MOC-31 are useful immunohistochemical markers for differentiating chromophobe RCC from oncocytoma. MATERIALS AND METHODS: We selected 23 chromophobe RCCs, 8 oncocytomas, and 25 clear cell RCCs and performed immunohistochemical staining for caveolin-1 and MOC-31. RESULTS: Caveolin-1 was positive in 20 (87%) of 23 chromophobe RCCs, 0 of 8 oncocytomas, and 21 (84%) of 25 clear cell RCCs. MOC-31 was positive in 22 (96%) of 23 chromophobe RCCs, 2 (25%) of 8 oncocytomas, and 14 (56%) of 25 clear cell RCCs. There was a statistically significant difference in the expression of caveolin-1 and MOC-31 between chromophobe RCC and oncocytoma (p<0.001). In addition, clear cell RCC was also significantly different from oncocytoma in the expression of caveolin-1 (p<0.001) and was significantly different from chromophobe RCC in the expression of MOC-31 (p<0.001). CONCLUSIONS: Caveolin-1 and MOC-31 can be useful markers in the differential diagnosis of chromophobe RCC, oncocytoma, and clear cell RCC.