Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

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IMPACT OF HORMONAL RECEPTOR STATUS AND Ki-67 EXPRESSION ON DISEASE FREE SURVIVAL IN PATIENTS AFFECTED BY HIGH-RISK ENDOMETRIAL CANCER

10.26226/morressier.599bdc7bd462b80296ca12cc ◽

2017 ◽

Author(s):

Violante di Donato

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Disease Free Survival ◽

Ki 67 ◽

Free Survival ◽

Receptor Status ◽

Hormonal Receptor ◽

Hormonal Receptor Status ◽

Disease Free

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Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival in Patients Affected by High-risk Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001191 ◽

2018 ◽

Vol 28 (3) ◽

pp. 505-513 ◽

Cited By ~ 7

Author(s):

Violante Di Donato ◽

Valentina Iacobelli ◽

Michele Carlo Schiavi ◽

Vanessa Colagiovanni ◽

Irene Pecorella ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Depth Of Invasion ◽

Prognostic Impact ◽

Ki 67 ◽

Free Survival ◽

Gynecology And Obstetrics ◽

Disease Free

ObjectivesThe aim of this study was to evaluate the immunohistochemical (IHC) expression of Ki-67, estrogen receptors α (ERsα), and progesterone receptors (PRs) in high-risk endometrial cancer patients and to assess their prognostic impact.Methods/MaterialsImmunohistochemical expression of Ki-67, ERsα, and PRs was evaluated in primary untreated endometrial cancer. The correlation among IHC staining and risk factors of recurrence such as age, Federation International of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread was assessed.ResultsEighty-two patients were available for the analysis. Mean ± SD age was 65.05 ± 10.48 years. The IHC assessment revealed a lack of ERα in 46.3% and of PR in 48.7% as well as a high Ki-67 in 31.7%. Loss of ERα and PR was associated with a significant higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a deeper myometrial invasion. Analysis of the interrelationship between receptor immunonegativity revealed a relevant association of ERα immunolocalization with PR and with a high Ki-67 expression. The present study also showed that loss of ERα (P = 0.003), advanced Federation International of Gynecology and Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent prognostic factors of a shorter disease-free survival. Importantly, loss of ERα, loss of PR, and a high Ki-67 were correlated with a higher incidence of distant recurrence.ConclusionsA systematic immunohistochemistry should be a key step in the therapeutic algorithm and could contribute to the identification of high-risk tumors.

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Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation

10.20944/preprints201810.0565.v1 ◽

2018 ◽

Author(s):

Daiki Mochizuki ◽

Yuki Misawa ◽

Hideya Kawasaki ◽

Atsushi Imai ◽

Shiori Endo ◽

...

Keyword(s):

Head And Neck Cancer ◽

Rna Interference ◽

Head And Neck ◽

Neck Cancer ◽

Univariate Analysis ◽

Disease Free Survival ◽

Rank Test ◽

Dna Hypermethylation ◽

Free Survival ◽

Disease Free

EZH2 overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We previously analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (P < 0.001) and the methylation index of tumor suppressor genes (P < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (P = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, P < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; P < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

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Disease Free Survival of Stage I Endometrial Cancer after Surgery with or without Adjuvant Treatment

Folia Medica Indonesiana ◽

10.20473/fmi.v55i1.24373 ◽

2021 ◽

Vol 55 (1) ◽

pp. 37

Author(s):

Woraluk Moradokkasem ◽

Nungrutai Saeaib ◽

Tippawan Liabsuetrakul

Keyword(s):

Endometrial Cancer ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Stage I ◽

Rank Test ◽

Free Survival ◽

Factors Associated ◽

Disease Free ◽

Better Than

This study aimed to define the disease free survival (DFS) and factors associated with recurrence in stage I endometrial cancer after surgery with and without adjuvant treatment. The demographic data, pathological results, adjuvant treatment (AT) and the outcome of patients with endometrial cancer stage I after surgery in Songklanagarind Hospital between January 2002 and July 2014 were collected. The DFS was analyzed by survival analysis and represented by Kaplan–Meier curves. The difference of DFS between AT and non-adjuvant treatment (NAT) groups was tested by the log-rank test. Distributions of risk factors by AT and recurrent status were analyzed using chi-square or Fisher exact tests for discrete factors, and unpaired t or Wilcoxon rank-sum tests for continuous factors. The 5-year DFS was; 91.6%, from a total of 268 patients. DFS in the NAT group was significantly better than that in the AT group (95.2 versus 86.5%, p-value = 0.01). Factors associated with recurrence in the NAT group were age, tumor grading, tumor size, and presence of lymphovascular involvement. Among the AT group, age and ratio of myometrial invasion were associated with recurrence. DFS in NAT was better than in AT and the potential factors associated with recurrence, after surgery with or without AT, were not the same.

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Disease Free Survival of Stage I Endometrial Cancer after Surgery with or without Adjuvant Treatment

Folia Medica Indonesiana ◽

10.20473/fmi.v55i1.12553 ◽

2019 ◽

Vol 55 (1) ◽

pp. 37

Author(s):

Woraluk Moradokkasem ◽

Nungrutai Saeaib ◽

Tippawan Liabsuetrakul

Keyword(s):

Endometrial Cancer ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Stage I ◽

Rank Test ◽

Free Survival ◽

Factors Associated ◽

Disease Free ◽

Better Than

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Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation

International Journal of Molecular Sciences ◽

10.3390/ijms19123707 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3707 ◽

Cited By ~ 8

Author(s):

Daiki Mochizuki ◽

Yuki Misawa ◽

Hideya Kawasaki ◽

Atsushi Imai ◽

Shiori Endo ◽

...

Keyword(s):

Head And Neck Cancer ◽

Rna Interference ◽

Head And Neck ◽

Neck Cancer ◽

Univariate Analysis ◽

Disease Free Survival ◽

Rank Test ◽

Dna Hypermethylation ◽

Free Survival ◽

Disease Free

Enhancer of Zeste homologue 2 (EZH2) overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibition of EZH2 is a potentially effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (p < 0.001) and the methylation index of tumor suppressor genes (p < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (p = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, p < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; p < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

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Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

Journal of Translational Medicine ◽

10.1186/s12967-021-02722-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Weiwei Feng ◽

Nan Jia ◽

Haining Jiao ◽

Jun Chen ◽

Yan Chen ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Tumor Recurrence ◽

Disease Free Survival ◽

Circulating Tumor Dna ◽

Plasma Samples ◽

Free Survival ◽

Tumor Relapse ◽

Disease Free ◽

Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

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High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0704-oa ◽

2013 ◽

Vol 137 (12) ◽

pp. 1761-1769 ◽

Cited By ~ 20

Author(s):

Ronghui Xia ◽

Rongrui Zhou ◽

Zhen Tian ◽

Chunye Zhang ◽

Lizhen Wang ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Distant Metastasis ◽

Survival Data ◽

Histone H3 ◽

Disease Free Survival ◽

Rank Test ◽

Free Survival ◽

Salivary Adenoid Cystic Carcinoma ◽

Adenoid Cystic ◽

Disease Free

Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.

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Relationship between Ribosomal Protein S6-pS240 Expression and other Prognostic Factors in Non-Special Type Invasive Breast Cancer

Breast Care ◽

10.1159/000491427 ◽

2018 ◽

Vol 14 (3) ◽

pp. 171-175

Author(s):

Frederik Cuperjani ◽

Lumturije Gashi ◽

Fisnik Kurshumliu ◽

Shemsedin Dreshaj ◽

Fitim Selimi

Keyword(s):

Breast Cancer ◽

Ribosomal Protein ◽

Invasive Breast Cancer ◽

Menopausal Status ◽

Treatment Protocol ◽

Prognostic Index ◽

Disease Free Survival ◽

Ki 67 ◽

Free Survival ◽

Disease Free

Background: The aim of this study was to investigate the immunohistochemical expression of ribosomal protein (RP) S6-pS240 in non-special type invasive breast cancer in relation to other prognostic markers and gain new insights to facilitate more individualized treatment. Methods: The following clinical and histopathological parameters of 120 patients were determined: S6-pS240 expression, age, menopausal status, tumor size and grade, TNM stage, Nottingham Prognostic Index (NPI), lymph node stage, estrogen and progesterone receptor (ER/PR) expression, HER2/neu amplification, lymphovascular invasion, and proliferative index as measured by Ki-67. Treatment protocol and disease-free survival were evaluated accordingly. Results: Significant positive correlations were seen between S6-pS240 expression and Ki-67 values (rho = 0.530, p < 0.001), and NPI (rho = 0.370, p < 0.001) and HER2/neu amplification (rho = 0.368, p < 0.001). A negative correlation was found between S6-pS240 and ER/PR expression (rho = 0.362, p < 0.001). Patients with negative RP S6-pS240 expression had significantly longer disease-free survival (log-rank test, p = 0.005). Conclusion: Immunohistochemical analysis of RP S6-pS240 is a valuable additional prognostic marker in patients with invasive breast cancer. Routine use of S6-pS240 immunohistochemistry is recommended.

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