IMP3 expression was frequently observed in gastric cancer and was associated with poor prognostic clinicopathological features. A survival benefit with HER2 therapy should be expected for the minority of patients with IMP3 positive specimens. Studies should be conducted to evaluate the response to HER2 therapy of gastric cancer expressing IMP3.
Epithelial cell adhesion molecule (EpCAM) has been used as diagnostic/prognostic marker and therapeutic target. The aim of the present study was to compare immunoreactivity of antibodies against distinct epitopes in the ectodomain of EpCAM for detection of carcinoma from different primary sites and of different histological types in effusions and peritoneal wash. Two antibodies against epitopes in the EGF-like domain I (clones Moc-31 and Ber-EP4) and one antibody against the epitope in the cysteine-poor region (158210) of EpCAM were used (all commercially available). Independently of the clone used, EpCAM overexpression was observed in almost all samples when all the adenocarcinoma samples were analyzed together. By using Moc-31, EpCAM overexpression was observed in all samples of adenocarcinoma. Absence of EpCAM overexpression was observed in a few adenocarcinoma samples at some sites of tumor origin, including ovary, breast and stomach, when Ber-EP4 and 158210 were used. Regarding carcinomas aside from adenocarcinomas, histological types, such as squamous cell, urothelial and small cell carcinoma showed different degrees of EpCAM expression according to the antibody used. In squamous cell carcinoma, overexpression was observed only with the clone 158210. It was concluded that, overall, most samples of metastatic carcinoma from effusions showed overexpression of EpCAM. However, there are significant variations in its detection according to the primary site, histological type of the carcinoma and depending on the antibody used. Thus, the use of more than one type of anti-EpCAM antibody would increase the chance of its detection in metastatic carcinoma effusion.FABIANA PIRANI CARNEIRO 1-3 , MARIA IMACULADA
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.
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.
The incidence of head and neck cancer as well as its mortality rates continues to increase, evidencing the need for diagnostic and prognostic markers that can improve clinical management of these patients. Histone Methyltransferases (HMT) are responsible for the methylation of histone tails, a mechanism important for the regulation of gene transcription, cell differentiation and proliferation. Although alterations on these enzymes have been associated with many types of cancer, their relationship with head and neck carcinogenesis is not yet understood. SUV420H1 and SUV420H2 are members of the SUV family of HMTs that contain the conserved SET domain, which catalyzes the addition of methyl groups to specific lysine residues, leading to chromatin compaction and gene repression. In the present study, we investigated the tissue expression profile of SUV420H1 and SUV420H2 using immunohistochemistry in 10 formalin-fixed paraffin-embedded human oral cancer samples and adjacent non-tumor tissues. We also investigated the alterations of SUV420H1 and SUV420H2 genes in head and neck cancer with in silico analyses from public databases. Immunohistochemistry revealed moderate to strong SUV420H1 and SUV420H2 expression in the majority of oral cancer cells, mainly with cytoplasmic staining in the invading tumor cells. In silico analyses using data from 530 head and neck squamous cell carcinoma samples (The Cancer Genome Atlas - TCGA, via cBioPortal) revealed that amplification is the most frequent genetic alteration in SUV420H1. Considering all known lysine methyltransferases, SUV420H1 was among the top three with the highest frequency of amplification. For SUV420H2, the frequency for amplification and deletion alterations was similar. The gene expression level of these methyltransferases was also analyzed. SUV420H1 showed a high expression of mRNA in head and neck cancer samples, with a moderate correlation (R: 0.588) between genetic copy number alteration and mRNA level. SUV420H2 did not show significant altered expression. In addition, SUV420H1 mRNA overexpression was associated with decreased overall survival in head and neck cancer patients (p: 0.0233). Since these enzymes are important in chromatin compaction and gene transcription repression, an increase in their expression level, as detected in this study, could lead to changes in histone methylation pattern, resulting in aberrant silencing of genes essential to maintain normal cellular function, such as tumor suppressor genes. Taken together, our data indicates a possible role of SUV420H1 in head and neck carcinogenesis, with the potential to be used as a prognostic marker for the disease. Citation Format: Doralina do Amaral Rabello Ramos, Beatriz Itai Haupt Ribeiro, Tércia Maria Mendes Lousa de Castro, Vívian D'Afonseca da Silva Ferreira, Gustavo Henrique Soares Takano, Eliza Carla Barroso Duarte, Fabiana Pirani Carneiro, Fábio Pittella Silva. Molecular analysis of histone methyltransferases SUV420H1 and SUV420H2 and their potential as prognostic markers in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2398. doi:10.1158/1538-7445.AM2017-2398
We showed that cytoplasmic laminin-5 expression should not be used as a criterion of malignancy and is not useful in distinguishing pseudocarcinomatous hyperplasia from microinvasive and well-differentiated SCC.
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