• Title, Summary, Keyword: prognostic marker

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Smudge cell percentage as a surrogate marker for ZAP-70 expression in patients with chronic lymphocytic leukemia

  • Al-Kahiry, Waiel;Tawfik, Hadeel Said;Sharshira, Homam;Ghanem, Amal;El-Gammal, Maha;Mikhael, Irene Lewis
    • BLOOD RESEARCH
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    • v.53 no.3
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    • pp.218-222
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    • 2018
  • Background This study aimed to evaluate the prognostic value of smudge cell percentage as a surrogate marker for zeta-chain-associated protein kinase 70 (ZAP-70) expression in chronic lymphocytic leukemia (CLL) patients. Methods Sixty three newly diagnosed CLL patients were investigated at the Hematology Department of the Medical Research Institute of Alexandria University with complete blood count, lactate dehydrogenase, ${\beta}_2$ microglobulin levels, ZAP-70 expression, and estimation of the percentage of smudge cells. Results The percentage of smudge cells ranged from 2 to 58% with a mean of $24.03{\pm}13.98%$. Higher percentages of smudge cells (>30%) were statistically significantly associated with markers of better prognosis (negative ZAP-70, early-stage disease according to the Binet and Rai staging systems, as well as low and intermediate risk CLL prognostic index). The percentage of smudge cells showed significantly negative correlation with the ZAP-70 expression and higher area under the curve for prediction of ZAP-70 positivity with better survival for 36 months in patients with >30% smudge cells. Conclusion The percentage of smudge cells at presentation of newly diagnosed CLL patients could be used as a surrogate marker for ZAP-70 expression and an additional prognostic marker for disease progression.

Prognostic Involvement of Nucleophosmin Mutations in Acute Myeloid Leaukemia

  • Shahab, Sadaf;Shamsi, Tahir Sultan;Ahmed, Nuzhat
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5615-5620
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    • 2013
  • Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a molecular chaperone and is mostly found in nucleoli. NPM also involved in the maturation of preribosomes and duplication of centrosomes. Furthermore, it is also active in control and regulation of the ARF-p53 tumor suppressor pathway. A high rate of incidence and prognostic involvement is reported by various authors in AML patients. In AML it behaves as a favorable prognostic marker. NPM mutations are more frequently associated with normal-karyotype AML and are usually absent in patients having abnormal or poor cytogenetic. NPM mutations are not frequent in other hematopoietic tumors. Two main types of mutations have been described to date. Both of these cause abnormal cytoplasmic localization of NPM1. Their high incidence rate in normal karyoptype and their favorable nature m ake those mutations hot spot or front face mutations which should be checked before treatment starts.

TGF-β-activated Kinase-1: A Potential Prognostic Marker for Clear Cell Renal Cell Carcinoma

  • Wei, Can;Lai, Yong-Qing;Li, Xian-Xin;Ye, Jiong-Xian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.315-320
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    • 2013
  • Background: TGF-${\beta}$-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. Methods: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. Results: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. Conclusions: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.

Survivin, Possible Marker and Prognostic Factor in Oral Squamous Cell Carcinomas

  • Kim, Young-Youn;Kim, Myung-Jin;Choi, Keum-Kang;Hong, Seong-Doo;Myoung, Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.34 no.1
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    • pp.71-82
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    • 2008
  • Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clini-co-pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients' clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.

Expression of DNA Methylation Marker of Paired-Like Homeodomain Transcription Factor 2 and Growth Receptors in Invasive Ductal Carcinoma of the Breast

  • Rahman, Wan Faiziah Wan Abdul;Fauzi, Mohd Hashairi;Jaafar, Hasnan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8441-8445
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    • 2014
  • Background: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). Methods: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH). Results: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). Conclusion: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome

  • Park, Hee Sue;Choi, Jungeun;See, Cha-Ja;Kim, Jung-Ah;Park, Si Nae;Im, Kyongok;Kim, Sung-Min;Lee, Dong Soon;Hwang, Sang Mee
    • Annals of Laboratory Medicine
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    • v.37 no.3
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    • pp.195-203
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    • 2017
  • Background: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA. Methods: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated. Results: MDS patients had shorter interphase TL than normal healthy donors (P <0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P =0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P =0.003, 0.001, 0.005, 0.005, and 0.013, respectively). Conclusions: The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS.

Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer

  • Kos, Fahriye Tugba;Hocazade, Cemil;Kos, Mehmet;Uncu, Dogan;Karakas, Esra;Dogan, Mutlu;Uncu, Hikmet Gulsen;Ozdemir, Nuriye;Zengin, Nurullah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3997-4002
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    • 2015
  • Background: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. Results: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ${\geq}3.24$) and PNI (<49.5 or ${\geq}49.5$). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). Conclusions: NLR (${\geq}3.24$) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

Analysis of Differential BRAFV600E Mutational Status in Papillary Thyroid Carcinoma

  • Jang, Hye-Lim;Kim, Tai-Jeon;Shin, Jae-Ho;Kim, Chul
    • Korean Journal of Clinical Laboratory Science
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    • v.44 no.2
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    • pp.75-80
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    • 2012
  • Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, accounting for 95% or more of malignancies in Korea. Recently, many thyroid cancers have been detected owing to the widespread use of ultrasonography in health surveillance. The objective of this study was to evaluate the association of known prognostic factors with the $BRAF^{V600E}$ mutation and its association features in Korean patients with papillary thyroid carcinomas. The $BRAF^{V600E}$ mutation was detected in 69.1% (256 of 370) of PTC cases. In univariate analysis, the $BRAF^{V600E}$ mutation was significantly associated with tumor size (p < 0.05) and sex. However, it was not significantly associated with other established risk factors, such as age, extrathyroidal extension, and lymph node metastasis. This finding supports the idea that the BRAF mutation plays a role in the early stage of PTC development. This relationship deserves further investigation to clarify whether $BRAF^{V600E}$ is a useful risk factor or prognostic marker for PTC.

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S100A14 Promotes the Growth and Metastasis of Hepatocellular Carcinoma

  • Zhao, Fu-Tao;Jia, Zhan-Sheng;Yang, Qun;Song, Le;Jiang, Xiao-Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3831-3836
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    • 2013
  • Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.

Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

  • Piao, Yong-Rui;Piao, Long-Zhen;Zhu, Lian-Hua;Jin, Zhe-Hu;Dong, Xiu-Zhe
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3897-3901
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    • 2013
  • Background: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. Methods: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. Results: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P<0.001). High TIM-3 expression was an independent predictor of both recurrence-free survival and progression-free survival. TIM-3 protein was expressed in both prostate cancer cell lines and knockdown suppressed their proliferation and invasion capacity. Conclusions: TIM-3 expression is associated with a poor prognosis in prostate cancer. Taken together, our resutlts indicate that TIM-3 is a potential prognostic marker in prostate cancer.