Expression of CTAG1B clone EPR13780 versus DDIT3 gene rearrangement distinguishes myxoid liposarcoma from its mimics with detection of novel DDIT3 gene copy number variations.

Myxoid liposarcoma (MLPS) has different patterns that are often difficult to distinguish from other soft tissue lesions. MLPS is characterized by a reciprocal translocation involving the DNA Damage Inducible Transcript 3 gene (DDIT3) that can be detected using fluorescent in situ hybridization (FISH). Recently, the marker for cancer testis antigen 1b (CTAG1B) was found to be expressed in MLPS. The aim of the present study was to assess the potential use immunohistochemistry (IHC) for CTAG1B expression and DDIT3 rearrangement to diagnose MLPS and distinguish it from similar lesions. Out of 29 cases including MLPS and its mimics, CTAG1B was expressed in 92.86% of cases of MLPS and 20% of its mimics. DDIT3 rearrangement was 100% sensitive and 92.86% specific in distinguishing MLPS from its mimics. The DDIT3 rearrangement was found to be more sensitive but less specific than cytoplasmic expression of CTAG1B marker. DDIT3 polysomy and amplification were detected in some cases. Therefore, both CTAG1B expression and FISH for DDIT3 gene can be used to distinguish MLPS from similar tumors. The use of both immunohistochemistry for CTAG1B in addition to DDIT3 gene rearrangement detection by FISH was more specific than using either of them alone. However, the DDIT3 gene rearrangement alone was the most sensitive test for distinguishing MLPS from its mimics.

Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases.

Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason, early detection of the metastatic lesions is crucial to improve patients' life span as well as quality of life. Many markers were proposed to be used as biomarkers for metastatic BC lesions, however many of them lack organ specificity. This highlights the need for novel markers that are more specific in detecting disseminated BC lesions. Here, we investigated mammaglobin-1 expression as a potential and specific marker for metastatic BC lesions using our patient cohort consisting of 30 newly diagnosed BC patients. For all patients, bone marrow (BM) aspiration, BM biopsy stained by H&E and BM immunohistochemically stained for mammaglobin-1 were performed. In addition, the CA15-3 in both serum and bone marrow plasma was also evaluated for each patient. Indeed, mammaglobin-1 immuno-staining was able to detect BM micrometastases in 16/30 patients (53.3%) compared to only 5/30 patients (16.7%) in BM biopsy stained by H&E and no cases detected by BM aspirate (0%). In addition, our results showed a trend of association between mammaglobin-1 immunoreactivity and the serum and BM plasma CA15-3. Further validation was done using large publicly available databases. Our results showed that mammaglobin-1 gene expression to be specifically upregulated in BC patients' samples compared to normal tissue as well as samples from other cancers. Moreover, our findings also showed mammaglobin-1 expression to be a marker of tumour progression presented as lymph nodes involvement and distant metastasis. These results provide an initial evidence for the use of mammaglobin-1 (SCGB2A2) immunostaining in bone marrow as a tool to investigate early BM micrometastases in breast cancer.

VCAM-1 and eosinophilia in diffuse sino-nasal polyps.

The objective of our study was to investigate: the expression of vascular cell adhesion molecule-1 (VCAM-1) in diffuse sino-nasal polyps; the relation between VCAM-1 and selective eosinophilia in diffuse sino-nasal polyps; the effect of eosinophilia and VCAM-1 expression on recurrence of diffuse sino-nasal polyps following treatment. Fifty patients with diffuse sino-nasal polyps were included in the study. Biopsies were taken from the polyps and the inferior turbinate mucosa of each patient and were studied by immunohistochemical staining for detection of VCAM-1 expression on the blood vessels, as well as by hematoxylin and eosin (H&E) staining for detection of eosinophils. The percentage of blood vessels expressing VCAM-1 and the number of eosinophils in the polyps were detected and correlated and then compared to the corresponding numbers in the inferior turbinates. All patients were treated by endoscopic ethmoidectomies followed by local steroids for 1 year. Recurrence of polyps was monitored during the post-operative follow-up period. The quantitative expression of VCAM-1 and number of infiltrating eosinophils were compared in patients who developed recurrent polyps and those who did not. VCAM-1 was expressed in the polyps but not significantly higher than in the inferior turbinates of the patients or the controls. Eosinophils were significantly higher in the polyps compared to the inferior turbinates. No correlation was found between the expression of the VCAM-1 and the number of eosinophils. VCAM-1 expression was significantly higher in patients developing recurrent polyps. No significant difference was found in the number of infiltrating eosinophils between patients developing and those not developing recurrent polyps. VCAM-1 is expressed in polyps but not significantly higher than its expression in the inferior turbinate mucosa. VCAM-1 expression in diffuse sino-nasal polyps cannot on its own explain the selective eosinophilia detected in this disease. High VCAM-1 expression in diffuse sino-nasal polyps may be an indicator of a higher probability of polyps recurrence. Degree of eosinophilic infiltration cannot be taken as such an indicator.

Ser-249 TP53 and CTNNB1 mutations in circulating free DNA of Egyptian patients with hepatocellular carcinoma versus chronic liver diseases.

Circulating free DNA (CFDNA) has been shown to be a good source of liver tissue-derived DNA in African and Asian patients with chronic liver disease or HCC. In Egypt, HCC is a frequent carcinoma and mostly occur in the context of chronic infection by HCV, a widespread infection in the Egyptian population. Here we have examined the presence of mutations in TP53 at codon 249 (Ser-249, considered as a hallmark of mutagenesis by aflatoxin) and in CTNNB1 (gene encoding beta-catenin) in CFDNA of patients with HCC or chronic liver disease, from Alexandria, Egypt. The DNA concentrations were significantly higher in HCC patients compared to HBV and HCV carriers without cancer, and to sero-negative individuals. Ser-249 TP53 mutations were determined using PCR-restriction digestion (RFLP) in CFDNA of 255 subjects, and confirmed by sequencing. Ser-249 was found in CFDNA of 12 subjects (4.8%), with the highest prevalence in subjects with chronic liver disease and infection by HBV (6/36; 16.7%) Mutations in CTNNB1 were examined using PCR combined to DHPLC and followed by sequencing. No mutations were found in CTNNB1 neither in CFDNA or in tumour tissue. In parallel, studies on DNA extracted from 20 HCC biopsies showed the presence of ser-249 mutation in two cases (10%). These results indicate that mutagenesis by aflatoxin may play a role in hepatocarcinogenesis in Egypt, and CFDNA may serve as a convenient source of material in monitoring the effects of aflatoxin exposure and viral infections in chronic liver disease and cancer.