ABSTRACT
This study highlights the prognostic impact of FOXP3 and CD68 expression in DLBCL, NOS and in its GCB and non-GCB subtypes. This may help the development of individualized therapy, prognostic prediction and therapy stratification.
Subject(s)
Germinal Center , Lymphoma, Large B-Cell, Diffuse , Humans , Germinal Center/metabolism , Germinal Center/pathology , Prognosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Forkhead Transcription Factors/metabolismABSTRACT
BACKGROUND: CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC). METHODS: This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification. RESULTS: High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030). CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000). CONCLUSION: EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.
Subject(s)
ErbB Receptors , Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/genetics , Prognosis , Retrospective Studies , In Situ Hybridization, Fluorescence , ErbB Receptors/genetics , ErbB Receptors/metabolism , Biomarkers , Ovarian Neoplasms/metabolism , Epithelial-Mesenchymal Transition/genetics , Biomarkers, Tumor/metabolism , Cell Line, TumorABSTRACT
BACKGROUND: Metastatic adenocarcinoma (MAC) accounts for most cases of malignant effusions. Sometimes, it can be difficult to distinguish MAC from reactive mesothelial cells (RMC) in cytologic specimens. Our aim was to assess the diagnostic performance of a novel immunohistochemical panel composed of claudin-4 and EZH2 in differentiating MAC from RMC in effusion cytology. METHODS: A total of 80 cases of serous effusions (48 MAC and 32 RMC) were included. Immunohistochemistry using claudin-4 and EZH2 was performed on cell block sections of these cases. Assessment of staining patterns, intensity and percentage of target cells stained was done. RESULTS: Claudin-4 showed membranous staining in 46/48 of MAC and 1/32 of RMC. High EZH2 (≥ 50% of target cells) was detected in 42/48 MAC and 2/32 RMC. For the discrimination between MAC and RMC, claudin-4 exhibited 95.8% sensitivity and 96.9% specificity, high-EZH2 exhibited 87.5% sensitivity and 93.8% specificity, while the combination of both claudin-4 and high EZH2 showed 100% sensitivity and 90.6% specificity. CONCLUSION: Claudin-4 shows high sensitivity and specificity in differentiation between MAC and RMC in effusion cytology, and might be useful as a solitary marker for MAC. Adding EZH2 to claudin-4 increases the sensitivity to 100%. However, the interpretation of EZH2 results can be challenging due to its focal expression in RMC and inflammatory cells.
Subject(s)
Mesothelioma , Pleural Effusion, Malignant , Biomarkers, Tumor/metabolism , Claudin-4 , Cytodiagnosis/methods , Diagnosis, Differential , Enhancer of Zeste Homolog 2 Protein , Humans , Immunohistochemistry , Mesothelioma/pathology , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/pathology , Sensitivity and SpecificityABSTRACT
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ABSTRACT
Chromosomal aberrations (CAs) in blood lymphocytes have been shown to be associated with overall cancer risk and aging. However, their relationship to bladder cancer risk remains to be elucidated. In a case-control study of bladder cancer in Egypt, we examined the relationship between the increased frequency of CAs in blood lymphocytes and bladder cancer risk. High frequency of CAs was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 3.90, 95% confidence interval (CI) = 2.65-5.73]. The associations were somewhat stronger in squamous cell carcinomas (SCC, OR = 4.90) than in urothelial carcinomas (UC, OR = 3.62). We also identified chromosome specific CAs for chromosomes 3, 4, 5, 8, 9, 10, 11, 12, 17, 19 that were significantly associated with an increased risk of bladder cancer. We observed particularly strong associations between aberrations of chromosomes 12, 13, 17 and risk of SCC (OR = 7.06, 6.91 and 6.23, respectively). CONCLUSION: increased frequency of chromosomal aberrations in blood lymphocytes was significantly associated with bladder cancer risk. Overall and chromosome specific aberrations in blood lymphocytes may be a unique set of biomarkers for risk assessments of SCC and UC.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Chromosome Aberrations/statistics & numerical data , Urinary Bladder Neoplasms/genetics , Aged , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/epidemiology , Female , Humans , Lymphocytes/metabolism , Lymphocytes/pathology , Male , Middle Aged , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/epidemiologyABSTRACT
Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.
