Detection of micro-metastasis using cytokeratins (AE1/AE3) in haematoxylin & eosin-stained N0 lymph nodes of oral squamous cell carcinoma

Background & objectives: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies affecting the head-and-neck region, regional lymph nodes being an important prognostication factor dictating the survival rate. Despite an array of modalities used, clinically, radiographically and routine histopathologically, the detection of micro-metastasis (2-3 mm tumour cell deposits) in the lymph nodes often escapes identification. The presence of few of these tumour epithelial cells in the lymph nodes drastically increases mortality and alters treatment plan. Hence, the identification of these cells is of major prognostic significance for a patient. Thus, the present study was aimed to evaluate and detect the efficacy of the immunohistochemical (IHC) marker [cytokeratin (CK) AE1/AE3] over routine Hematoxylin & eosin (H & E) staining in detecting micro-metastasis in the lymph nodes of OSCC cases. Methods: Hundred H & E-stained N0 lymph nodes of OSCC cases treated with radical neck dissection were subjected to IHC with marker AE1/AE3 antibody cocktail for detecting micro-metastasis. Results: The IHC marker CK cocktail (AE1/AE3) did not demonstrate any positive reactivity for the target antigen in all the 100 H & E stained lymph node sections evaluated in the present study. Interpretation & conclusions: This study was undertaken to check the efficacy of IHC (CK cocktail AE1/ AE3) in the detection of micro-metastasis in lymph nodes that are found to be negative in routine H&E stained sections. The findings of this study suggest that the IHC marker AE1/AE3 did not prove to be useful to detect micro-metastasis in this study population

Assessment of Cytokeratin Expression in Carcinoma Breast

Breast cancer is the most common malignancy in females and an important cause of cancer deaths worldwide. With advances in oncopathology, breast cancers are now diagnosed and treated at a molecular level. To distinguish and subdivide the type of cancer with the suitable markers and to foresee its prognosis and therapeutic approach, cytokeratin can be used which is prognostic tumour marker and has a number of different advantages as it is an important IHC marker, cytokeratin (Ck) is epithelial intermediate filament, which is expressed in a tissue specific manner. Expression of the intermediate filaments, predominantly cytokeratins (Ck) reflects the epithelial cell type. In breast, the luminal epithelial cells express CK 8 / 18, CK 7 and CK 19, while basal cell expresses CK 5 / 6, CK 14 and CK 17. Bloom Richardson grading (BR) system has a powerful prognostic value. It is also incorporated in the algorithm for the determination in the use of adjuvant chemotherapy. Moreover, as a tumour marker cytokeratin can accurately predict disease status as it is easy, inexpensive and a reliable tool for efficient management. CK and BR grading can be used as cost effective diagnostic tools in hormone positive breast carcinoma for diagnosis as well as treatment. Very early detection of breast cancer reduces the mortality and morbidity.

Biochemical analysis of cytokeratin fragment 21-1 concentration and expression of cytokeratin 19 in oral potentially malignant disorders

Introduction: Cytokeratin fragment 21-1 (CYFRA21-1), a constituent of the intermediate filament protein is known to be elevated in cancer. In vitro cleavage of cytokeratin 19 (CK19) protein results in the release of it's fragments into the supernatants of premalignant cell lines. This study was designed with the aim to investigate the concentrations of CYFRA21-1 in serum and saliva of oral potentially malignant disorders (OPMD), to evaluate CK19 expression in tissues of the same patients and to correlate the levels of CYFRA21-1 concentration in serum and saliva with CK19 expression in OPMDs, and to compare it with oral squamous cell carcinoma (OSCC), which was taken as positive control. Materials and Methods: Concentration of CYFRA21-1 was measured in saliva and serum of 30 OPMD cases with five patients having OSCC using ELISA technique and analysis of CK19 protein expression in the tissue of same patients using immunohistochemical technique was done. Results: Concentration of CYFRA21-1 in saliva and serum with regard to CK19 protein expression in tissues was significantly higher in control group than in study groups. Conclusion: CYFRA21-1 can be used as a promising diagnostic molecule and as an adjunctive marker for early detection, disease staging, and monitoring

Nasopharyngeal undifferentiated carcinoma with sarcomatoid features: Pitfalls in the immunohistochemistry

@#We present a case of an undifferentiated subtype of non-keratinizing squamous cell carcinoma (NK-SCC) with sarcomatoid features in the nasopharynx in a 69-year-old man who was difficult to diagnose due to spindle-shaped malignant cells. He was admitted because of a right nasal obstruction and right headache, and imaging revealed a heterogeneously enhanced irregularly shaped mass at the nasopharynx. Histopathologically, the tumour was partially organised, and the tumour cells were epithelioid or spindle-shaped. Initially, we erroneously diagnosed the tumour as an angiosarcoma owing to its false-negative immunoreaction for cytokeratins and a mistaken interpretation for CD31. After in situ hybridization for Epstein-Barr virus was positive, a consultation and additional immunostaining (including re-staining for cytokeratin with varying dilutions) were performed, and the diagnosis was revised to NK-SCC with sarcomatoid features. We believe that sarcomatoid features may be observed in nasopharyngeal carcinoma and in this case, immunostaining using various epithelial markers is necessary and careful attention should be paid to the interpretation of immunostaining.

Analisis inmunohistoquimico de CK14 y CK19 en germen dentario y ameloblastoma / Immunohistochemical analysis of ck14 and ck19 in tooth germs and ameloblastoma

La odontogénesis es el proceso de formación de los órganos dentarios, en el cual se expresan diversas moléculas, dentro de las cuales encontramos las citoqueratinas 14 y 19 (CK14, CK19). Una vez concluido el proceso de formación del diente quedan restos del epitelio odontogénico, el cual se ha sugerido se encuentra implicado en el desarrollo del ameloblastoma, uno de los tumores odontogénicos más frecuentes. Se ha sugerido que las CK14 y CK19 tienen utilidad como marcadores de diferenciación ameloblástica, y podrían tener implicación dentro del comportamiento tumoral de los ameloblastomas. El objetivo del presente estudio fue describir los patrones de expresión inmunohistoquímica de estas dos citoqueratinas en gérmenes dentarios y ameloblastomas. Materiales y métodos. Se incluyeron 6 ameloblastomas sólidos multiquísticos y 5 gérmenes dentarios a los cuales se les realizó técnica de inmunohistoquímica para CK14 y CK19. Resultados. Este estudio permitió visualizar la inmunoexpresión de CK14 y CK19 en el epitelio y la negatividad en el ectomesénquima, tanto en los gérmenes dentarios como en ameloblastomas. También permitió concluir que CK19 puede ser considerada como un eficiente marcador de diferenciación ameloblástica, mientras que CK14 es gradualmente remplazada por CK19 en el epitelio interno del órgano del esmalte, evidenciándose marcada inmunoexpresión de esta última en ameloblastos secretores...

Introduction. Odontogenesis is the process by which teeth form, and where different molecules are expressed, among them some cytokeratins (CK) like CK14 and CK19. Remnants of odontogenic epithelium may persist once the development process is complete, which has been suggested to be involved in the development of ameloblastoma, one of the most common benign odontogenic tumours. It has been suggested that CK14 and CK19 are useful markers of ameloblast differentiation and that they could have implications for tumour behaviour. The aim of this study is to describe the patterns of immunohistochemical expression of these cytokeratins in tooth germs and ameloblastomas. Materials and methods. We worked with 6 solid multicystic ameloblastomas and 5 tooth germs. The immunohistochemistry technique was used to visualise CK14 and CK19. Results. We detected CK14 and CK19 immunoexpression in the epithelium and no expression in the ectomesenchyme in both tooth germs and ameloblastomas. It was concluded that CK19 can be considered an efficient marker of ameloblast differentiation, whereas CK14 is gradually replaced by CK19 in the inner epithelium of the enamel organ, showing strong immunoexpression in secretory ameloblasts...

Central odontogenic fibroma: Report of case with immunohistochemical study.

Objectives: To report a case of central odontogenic fibroma (COF) with immunohistochemical study. Clinical Presentation: We describe a case of epithelium‑rich type of COF in the posterior region of the mandible of a 39‑year‑old woman. Immunohistochemical examination showed the odontogenic epithelium to be positive for high‑molecular‑weight cytokeratins, vimentin and CD99, and negative for CAM5.2. The stroma contained some myofibroblasts and many fibroblast‑like cells positive for CD99. Conclusion: Our immunohistochemical findings, and especially the positive expression of vimentin from the epithelial cells of COF suggests that these cells are primordial. Last but not least, the presence of a relative small number of myofibroblasts in the stroma justifies the non‑aggressive behavior of the neoplasm and supports that a part of stromal collagen of COF is produced by these cells.

El valor de la inmunohistoquímica en el diagnóstico de carcinomas hepáticos primarios y secundarios / The value of immunohistochemistry in the diagnosis of primary and secondary liver carcinomas

Ante el reto diagnostico que presenta una neoplasia hepática que no es bien diferenciada, es este estudio se propone la utilización de un perfil de inmunohistoquímica que incluye citoqueratina (CK) 7, 19 y 20, as¡ como factor de transcripción tiroideo (TTF-1) para demostrar su eficacia en el diagnóstico diferencial de hepatocarcinomas, colangiocarcinomas y metástasis de adenocarcinoma y de ese modo facilitar los diagnóstico en la práctica diaria...

The clinical value of measurement of urine nuclear matrix protein 22 and urinary bladder cancer antigen content in patients of bladder transitional cell carcinoma / 中国综合临床

Objective To assess the feasibility of nuclear matrix protein 22(NMP22)and urinary bladder cancer,antigen (UBC) for the early diagnosis of bladder transitional cell carcinoma and its influencing factors.Methotis 105 subjects,including 60 patients of bladder cancer,25 patients of urological benign disease and 20 normal (healthy)individuals were enrolled in this study.Urine NMP22 and UBC wag assessed by enzyme-linked immunosorbent assay(ELISA).Urine NMP22 and UBC as well as exfoliocytology were conducted for the purpose to compare the sensitivity,specificity,positive and negative predictive value of these three ways.Results The sensitivity of NMP22(88.3%)and UBC(86.7%)were significantly better than exfolioeytology(40.0%,P<0.01).The specificity of NMP22,UBC and exfoliocytology were 80.0%,84.0%and 92.0%,respectively, the positive predictive values were 91.4%,92.9%and 92.3%,and the negative predictive values were 74.1%.72.4%and 38.9%.Conclusions NMP22 and UBC are sensitive,specific,simple,feasible and noninvasive diagnostic markers for the early detection of urinary bladder transitional cell cancer.

A Novel Monoclonal Antibody With a Mono-specificity for a 46 ku-Cytokeratin / 生物化学与生物物理进展

A mAb T2-2 was generated using hybridoma techniques, and its target was identified as a 46 ku-cytokeratin (CK), based on biochemical study and a completely overlapped binding pattern of mAb T2-2 with anti-pan-CKs antibodies. An epithelia-specificity of the mAb T2-2 was determined by screening 68 human normal and 65 tumor tissues using immunohistochemistry. Unlike most of anti-CKs antibodies, the mAb T2-2 recognized a mono-specific epitope only expressed on the 46 ku CK, suggesting that mAb T2-2 is superior to most anti-CKs antibodies that cross-reacted with many different kinds of CKs. In addition, it was found that the mAb T2-2 was multipurpose with a broad applicability to ELISA, immunohistochemistry, immunofluorescence, Western blotting, and was also compatible with various fixation reagents. These results strongly indicate that the mAb T2-2 has potential applications for studying CKs function and for diagnosis of tumor and other disorders.

Co-relationship between Expression of Keratins and Vimentin in Breast Cancer Tissures and Metastases of Breast Cancer / 한국유방암학회지

PURPOSE: the most important biological behavior of breast cancer is its invasive potential and many efforts was made to reveal the factors related with the invasiveness of breast cancer cells. Some researchers reported that intermediate filament biology could represent an emerging and exciting field in tumor biology with respect to tumor aggressiveness and invasiveness. There are some experimental evidences that co-expression of vimentin, a interfilament marker indicative of mesenchymal lineage, and cytokeratin interfilaments can be correlated with invasiveness and metastatic deposits. So, we tried to determine the role of intermediate filaments such as cytokeratins and vimentin with respect of bone marrow micrometastases. METHODS: Expression of cytokeratins 8, 18, 19 and viementin were immunohistochemically evaluated. Detection of bone marrow micrometastases was preformed through RT-PCR targeting mRNA of cytokeratin 19. In order to compare the study group by the expression extent of cytokeratins, the case expressing 50% or more of observed cells was classified into the case with high expression and the case expressing 49% or less was classified into the case with low expression. RESULTS: The only cytokeratin of high expression representing the risk of bone marrow micrometastases was cytokeratin 8. Vimentin expression by itself did not show any significance indicating bone marrow micrometastases. However, The cases possesing cytokeratin 8, 18, and 19 expression, altogether 75% or more showed a significantly high risk to bone marrow micrometastases. In that cases, addition of vimentin expression allowed a more higher possibility of bone marrow micrometastases. CONCLUSION: A high expression of cytokeratin 8 among cytokeratins was related with bone marrow metastases. However, vimentin expression by itself did not show any realtionship with bone marrow metastases. So, a further study is needed in order to reveal the role of vimentin expression in progression and metastases of breast cancer.

Combined use of urinary bladder cancer antigen,hyaluronic acid and survivin for the detection of bladder cancer / 中华泌尿外科杂志

Objective To assess the diagnostic value of combined testing of urinary bladder cancer antigen(UBC),hyaluronic acid(HA)and survivin in the detection of bladder cancer.Methods This study included 64 bladder cancer patients and 20 urinary benign disease patients.The examinations of urine UBC by enzyme-linked immunosorbent assay(ELISA),HA by radioimmunology assay,survivin by RT-PCR and urine cytology were performed in them.Results The sensitivity of UBC(85.9%,55/64),HA (89.1%,57/64)and survivin(93.8%,60/64)was significantly higher than that of urine cytology (40.6%,P＜0.01).The specificity of UBC,HA,survivin and urine cytology was 85.0%(17/20),80.0% (16/20),95.0%(19/20)and 95.0%(19/20),respectively;there was no significant difference among these 4 methods(P＞0.05).The sensitivity of UBC,HA and survivin was also significantly higher than that of urine cytology in different histologic stages and grades(P＜0.05).The sensitivity of UBC and survivin was not significantly different among different histologie stages and grades(P＞0.05).With regard to HA test, the sensitivity in G_2 and G_3 groups was significantly higher than G_1 group(P＜0.01),but there was no differ- ence between G_2 and G_3 groups(P＞0.05);and no difference among different histologic stages(P＞0.05). However,the sensitivity of cytology was improved with the higher grade of bladder cancer(P＜0.01);there was no difference among histologic stages(P＞0.05),By combined use of UBC,HA and survivin,both the sensitivity and specificity were 100%.Conclusions The study indicates that UBC,HA and survivin are better diagnostic markers for the early detection of urinary bladder cancer.These tests are simple,feasible and noninvasive with higher sensitivity and specificity.In addition,combined use of them can improve the diag- nostic sensitivity and specificity.