Background : Usual interstitial pneumonia (UIP) is a fatal progressive fibrotic disorder of the lung with unknown etiology and characterized by a poor response to conventional immunosuppressive therapy. The histologic hallmark of UIP is parchy distribution of subpleural fibrosis and fibroblastic foci(FBF) with interposed normal appearing lung. Because FBF is a collection of actively proliferating myofibroblasts, it can be a marker of activity and prognosis of UIP. However, there were contradictory reports about the correlation between the degree of FBF and survival. Therefore we performed this study to investigate the value of FBF as prognostic marker of UIP. Methods : This was a retrospective study on the 46 patients(M:F=33:13, mean age:$59{\pm}12$ years) with UIP diagnosed by the surgical lung biopsy at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the ATS/ERS classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) by the experienced pathologists who did not know the clinical findings were compared to the clinical data and the follow up course. Results : Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. At the univariate analysis, FVC, $D_Lco$, smoking history and the grade of FBF were significantly related to the survial. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking. However the multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. Conclusion : These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.
Background: CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta-analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. Materials and Methods: Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to estimate the effects. Results: A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95%CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95%CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95%CI=1.93-4.72, p<0.00001). Conclusions: Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.
The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes - germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients.
Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is implicated in the mechanisms of cellular DNA repair. Inactivation of this gene is involved in the development of many human cancers, including breast cancer. This study aimed to investigate the prognostic value of BRCA1 promoter hypermethylation and expression in breast cancer cases. Sixty-one breast cancers were examined for BRCA1 hypermethylation by methylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed for altered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Aberrant methylation status in BRCA1 was detected in 15 of 61 cases (24.6%), while reduced expression was found in 7 of 45 (15.6%). BRCA1 hypermethylation was statistically associated with tumor grade III (p=0.04), a high frequency of stage IIB (p=0.02), and triple-negative phenotype (OR= 3.64, 95%CI =1.1-12.3, p=0.03). Our findings indicated that BRCA1 promoter hypermethylation is a useful prognostic marker for breast cancer.
Na Young Kim;Dong Jin Im;Yoo Jin Hong;Byoung Wook Choi;Seok-Min Kang;Jong-Chan Youn;Hye-Jeong Lee
Korean Journal of Radiology
/
v.25
no.6
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pp.540-549
/
2024
Objective: This study investigated the feasibility and prognostic relevance of threshold-based quantification of myocardial delayed enhancement (MDE) on CT in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods: Forty-three patients with NIDCM (59.3 ± 17.1 years; 21 male) were included in the study and underwent cardiac CT and MRI. MDE was quantified manually and with a threshold-based quantification method using cutoffs of 2, 3, and 4 standard deviations (SDs) on three sets of CT images (100 kVp, 120 kVp, and 70 keV). Interobserver agreement in MDE quantification was assessed using the intraclass correlation coefficient (ICC). Agreement between CT and MRI was evaluated using the Bland-Altman method and the concordance correlation coefficient (CCC). Patients were followed up for the subsequent occurrence of the primary composite outcome, including cardiac death, heart transplantation, heart failure hospitalization, or appropriate use of an implantable cardioverter-defibrillator. The Kaplan-Meier method was used to estimate event-free survival according to MDE levels. Results: Late gadolinium enhancement (LGE) was observed in 29 patients (67%, 29/43), and the mean LGE found with the 5-SD threshold was 4.1% ± 3.6%. The 4-SD threshold on 70-keV CT showed excellent interobserver agreement (ICC = 0.810) and the highest concordance with MRI (CCC = 0.803). This method also yielded the smallest bias with the narrowest range of 95% limits of agreement compared to MRI (bias, -0.119%; 95% limits of agreement, -4.216% to 3.978%). During a median follow-up of 1625 days (interquartile range, 712-1430 days), 10 patients (23%, 10/43) experienced the primary composite outcome. Event-free survival significantly differed between risk subgroups divided by the optimal MDE cutoff of 4.3% (log-rank P = 0.005). Conclusion: The 4-SD threshold on 70-keV monochromatic CT yielded results comparable to those of MRI for quantifying MDE as a marker of myocardial fibrosis, which showed prognostic value in patients with NIDCM.
C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane protein which is overexpressed in several human malignancies. However, there are few data available on C4.4A expression and its relationship with progression in gastric cancer. Our study was designed to explore the expression of C4.4A in gastric cancer and to correlate it with clinical outcome. C4.4A expression was studied by quantitative real-time RT-PCR and immunohistochemistry for assessment of correlations with clinicopathological factors. C4.4A mRNA expression was significantly up-regulated in gastric cancer as compared with noncancerous tissue (p<0.05)., being observed in 107 (88.4%) of the 121 gastric cancer cases by immunohistochemistry. We found that the expression of C4.4A mRNA was correlated with size of the tumor, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, patients with overexpression of C4.4A has a significantly worse survival (p<0.05). Further multivariable analysis indicated that the expression of C4.4A was an independent prognostic indicator for gastric cancer (p<0.05). In conclusion, overexpression of C4.4A correlates with metastatic potential of gastric cancer and C4.4A could be a novel independent prognostic marker for predicting outcome.
Purpose: This study was to investigate the prognostic significance of the preoperative fibrinogen and systemic inflammation response index (F-SIRI) in a Chinese cohort of resectable gastric cancer. Materials and Methods: Baseline characteristics, preoperative fibrinogen levels and peripheral neutrophil, monocyte, and lymphocyte counts were retrospectively reviewed in 240 patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and SIRI were defined as 4.0 g/L and 1.2. Then patients with hyperfibrinogenemia (≥4.0 g/L) and high SIRI (≥1.2) were assigned with an F-SIRI of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), and 0 (neither abnormality), respectively. The prognostic value was examined by univariate and multivariate survival analysis. Results: Preoperative F-SIRI was significantly correlated with tumor size, fibrinogen level, and adjuvant chemotherapy. Whereas there was no significant difference in age, gender, tumor location or other characteristics between groups. In addition, high preoperative F-SIRI was significantly associated with worse disease-free survival (DFS) (hazard ratio [HR], 2.299; 95% confidence interval [CI], 1.482-3.566; P<0.001) and overall survival (OS) (HR, 2.461; 95% CI, 1.584-3.824; P<0.001) by univariate survival analysis. Moreover, it remained an independent predictor for impaired DFS (HR, 2.023; 95% CI, 1.273-3.215; P=0.003) and OS (HR, 2.341; 95% CI, 1.480-3.705; P<0.001) in multivariate Cox regression analysis. Conclusions: Preoperative F-SIRI could serve as a significantly prognostic marker for long-term survival in Chinese patients who underwent radical gastrectomy.
The clinical staging systems for oral squamous cell carcinoma is limited as a prognostic indicatior because of different biological characteristics of cancer in this region and variable microenvironment depending on subsites, there have been study to determine prognosis by evaluating malignancy, that is the nature of tumor cells. Many studies have been tried to determine prognostic indicator in various malignancies for the evaluation of differentiation capacity and the expression of oncogene product. EGF make a role in cellular growth and differentiation and to be essential in cellular survival. EGFR is an intergral membrane protein, stimulate cellular differentiation and hormonal secretion, and has structural homology with V-erb-B transforming protein. Recent reports have demonstrated that EGFR is overexpressed in stomach, breast, vagina, dermis, head and neck, genitourinary and lung tumors, and possibly used as a tumor marker. In head and neck region, most of studies were mainly carried out on laryngeal squamous cell carcinoma. In the present study, immunohistochemical study for EGFR and C-erb-B2 gene in paraffin sections of 45 squamous cell carcinoma in oral cavity was performed to evaluate the presense of EGFR and C- erb-B2 gene in this lesion, to evaluate them as a prognostic indicator by analysing the correlation between these expression and subsites, primary stages, clinical stages, pathologic grades, neck node metastasis, recurrences and treatment results, and to determine relation between EGFR and C-erb-B2 gene.
Subimerb, Chutima;Wongkham, Chaisiri;Khuntikeo, Narong;Leelayuwat, Chanvit;McGrath, Michael S.;Wongkham, Sopit
Asian Pacific Journal of Cancer Prevention
/
v.15
no.10
/
pp.4217-4224
/
2014
Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF ${\beta}1$, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.
Background: Development of squamous cell cancer of head and neck (SCCHN) is associated with human papillomavirus (HPV) infection, which in turn is closely related with expression of $p16^{INK4A}$. Loss of $p16^{INK4A}$ expression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated $p16^{INK4A}$ as a prognostic marker of treatment response and survival in our SCCHN patients with laryngeal, hypopharyngeal or nasopharyngeal cancers. Materials and Methods: 131 patients diagnosed with SCCHN between January 2,2006 and July 17, 2010 were examined for $p16^{INK4A}$. The median age was 60 years (15-82 years). Fifty one patients were stage I-II and 80 were stage III-IV. Immunohistochemical expression of $p16^{INK4A}$ was analyzed in pretreatment paraffin-embedded tumor blocks. The influence of $p16^{INK4A}$ status on disease-free survival, and overall survival after treatment was evaluated. Results: $p16^{INK4A}$ positivity was found in 58 patients (44%). Tumor-positivity for$ p16^{INK4A}$ was correlated with improved disease free survival (70.1 months vs 59 months) and improved overall survival (2, 3 and 5-year values; 77% vs 72%, 70% vs 63% and, 63% vs 55%; respectively). On multivariate analysis, stage was determined as independent prognostic factor for disease-free survival. Conclusions: Stage was the major prognostic factor on treatment response and survival in our patients. $p16^{INK4A}$ status predicts better outcome in laryngeal, hypopharyngeal or nasopharyngeal cancer cases treated with surgery plus adjuvant radiochemotherapy as well as with definitive radiation therapy and/or chemotherapy.
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