Overexpression of Special AT-Rich Sequence-Binding Protein 1 in Endometrial Cancer: A Clinicopathologic Study

ObjectiveSpecial AT-rich sequence-binding protein 1 (SATB1), as a genome organizer, serves important functions in tumor progression and metastasis. The SATB1 is overexpressed in various malignant tumors. However, the expression and prognostic value of SATB1 in endometrial cancer remain unknown. The aim of this study was to explore the prognostic values of SATB1 expression in endometrial cancer.Methods/MaterialsWe investigated the expression of SATB1 in 172 untreated endometrial cancer tissues and 25 normal endometrial tissues through immunohistochemical staining. We also analyzed the association of SATB1 level with clinicopathologic parameters and determined its prognostic significance.ResultSpecial AT-rich sequence-binding protein 1 was expressed in 78 (45.3%) of the 172 endometrial cancer samples, but not in the normal endometrial samples. The positive expression of SATB1 was associated with clinicopathologic factors, such as International Federation of Gynecology and Obstetrics stage, histological grade, myometrial invasion depth, lymph node metastasis, vascular/lymphatic invasion, and recurrence. The patients with positive SATB1 expression had worse overall survival and disease-free survival rates than the patients with negative SATB1 expression (P< 0.001 for both). Multivariate Cox analysis indicated that SATB1 was an independent parameter for overall survival (hazards ratio, 2.928; 95% confidence interval, 1.072–7.994;P= 0.036) and disease-free survival (hazards ratio, 2.825; 95% confidence interval, 1.111–7.181;P= 0.029).ConclusionsResults showed that SATB1 may be involved in tumor development and progression in endometrial cancer, may serve as a promising biomarker for predicting the prognosis of endometrial cancer patients, and thus may act as a novel target for treating endometrial carcinoma.

Download Full-text

Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis

Frontiers in Endocrinology ◽

10.3389/fendo.2021.691557 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fei Wang ◽

Xiaowu Xu ◽

Zeng Ye ◽

Yi Qin ◽

Xianjun Yu ◽

...

Keyword(s):

Overall Survival ◽

Confidence Interval ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Pancreatic Neuroendocrine Tumors ◽

Relapse Free Survival ◽

Free Survival ◽

Disease Free ◽

Combined Data

BackgroundPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.MethodsEligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.ResultsFourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, P = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, P < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, P = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, P = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.ConclusionsThis is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.

Download Full-text

HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients

Tumor Biology ◽

10.1177/1010428318757103 ◽

2018 ◽

Vol 40 (2) ◽

pp. 101042831875710 ◽

Cited By ~ 7

Author(s):

Karin Abbink ◽

Petra LM Zusterzeel ◽

Anneke J Geurts-Moespot ◽

Antonius E van Herwaarden ◽

Johanna MA Pijnenborg ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Confidence Interval ◽

Cancer Patients ◽

Recurrent Disease ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

Objective: To date, biomarkers are not routinely used in endometrial cancer diagnosis, prognosis, and follow-up. The purpose of this study was to evaluate whether serum HE4 was related to clinicopathological risk factors and outcome. Second, the role of serum HE4 and CA125 was assessed as indicator for recurrent disease during follow-up. Methods: A total of 174 patients with endometrial cancer between 1999 and 2009 were selected for this retrospective study. Serum HE4 and CA125 were analyzed at primary diagnosis, during follow-up, and at the time of recurrence. Correlations with clinicopathological factors were studied by univariate and multivariate survival analyses. Lead time was calculated in order to determine which serum marker was elevated prior to clinical detection of recurrent disease. Results: Serum levels of HE4 and CA125 were significantly associated with high tumor grade, myometrial invasion, lymph node involvement, and advanced stage (p < 0.01). HE4 was an independent prognostic factor for reduced disease-free survival and overall survival with hazard ratios of 2.96 (95% confidence interval: 1.18–7.99) and 3.27 (95% confidence interval: 1.18–9.02), respectively. At recurrence, 75% of the patients had an elevated HE4 compared to 54% with an elevated CA125. HE4 levels were more frequently elevated in patients with distant metastasis compared to local recurrences, 67% and 37%, respectively. Serum HE4 detected a recurrence with a median of 126 days earlier than clinical confirmation. Conclusion: Elevated serum HE4 is an independent risk factor for reduced disease-free survival and overall survival. HE4 seems to be superior to CA125 in the detection of recurrent disease during follow-up, mainly in high-risk endometrial cancer patients who are more prone to distant metastasis.

Download Full-text

Weight changes during chemotherapy for breast cancer

Sao Paulo Medical Journal ◽

10.1590/s1516-31802002000400005 ◽

2002 ◽

Vol 120 (4) ◽

pp. 113-117 ◽

Cited By ~ 25

Author(s):

Luciano José Megale Costa ◽

Paulo César Spotti Varella ◽

Auro del Giglio

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Body Weight ◽

Weight Gain ◽

Weight Change ◽

Prognostic Significance ◽

Disease Free Survival ◽

Weight Changes ◽

Free Survival ◽

Disease Free

CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8), adjuvant (n = 74) or palliative (n = 24) chemotherapy. INTERVETION: Review of medical records and gathering of clinical information, including patients’ body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 ± 1.42% (p = 0.21) of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001). In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 ± 1.19 % (p < 0.00001) per month, whereas in the metastatic (palliative) group, we observed a mean loss of 0.52 ± 1.21% (p = 0.11) of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy.

Download Full-text

Prospective Cohort Study of Pre- and Postdiagnosis Physical Activity and Endometrial Cancer Survival

Journal of Clinical Oncology ◽

10.1200/jco.20.01336 ◽

2020 ◽

Vol 38 (34) ◽

pp. 4107-4117

Author(s):

Christine M. Friedenreich ◽

Linda S. Cook ◽

Qinggang Wang ◽

Renée L. Kokts-Porietis ◽

Jessica McNeil ◽

...

Keyword(s):

Physical Activity ◽

Overall Survival ◽

Endometrial Cancer ◽

Cohort Study ◽

Disease Free Survival ◽

Activity Levels ◽

Recreational Physical Activity ◽

Free Survival ◽

Physical Activity Levels ◽

Disease Free

PURPOSE The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose (metabolic-equivalent task [MET]-hours/week/year), and change from pre- to postdiagnosis. METHODS We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities. RESULTS After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14 v ≤ 8 MET-hours/week/year; hazard ratio [HR], 0.54; 95% CI, 0.30 to 0.96; Ptrend = .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07; Ptrend = .06). Higher postdiagnosis recreational physical activity (> 13 v ≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64; Ptrend = .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75; Ptrend = .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels. CONCLUSION Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.

Download Full-text

FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20181640 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 2

Author(s):

Xuling Liu ◽

Hong Gao ◽

Jie Zhang ◽

Dongying Xue

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Sequence Similarity ◽

Prognostic Significance ◽

Disease Free Survival ◽

High Expression ◽

Mrna Levels ◽

Free Survival ◽

Ajcc Stage ◽

Disease Free

AbstractPrognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.

Download Full-text

Prevalence and Prognostic Value of HPV among Tunisian Patients with Laryngeal Cancer and Relationship between DNA HPV and p16, IGF-1R, Survivin, p53 Expressions

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489420918280 ◽

2020 ◽

Vol 129 (9) ◽

pp. 863-871

Author(s):

Mariem Ben Elhadj ◽

Asma Fourati ◽

Olfa El Amine ◽

Aida Goucha ◽

Ahmed El May ◽

...

Keyword(s):

Overall Survival ◽

Laryngeal Cancer ◽

Prognostic Significance ◽

Disease Free Survival ◽

Hpv Infection ◽

Clinicopathological Parameters ◽

Free Survival ◽

Hpv Dna ◽

Hpv Status ◽

Disease Free

Objectives: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored. In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. Methods: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. Results: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival ( P = .081) and long disease-free-survival ( P = .016) with a low rate of recurrence ( P = .006) than HPV– patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression ( P = .043). Conclusion: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.

Download Full-text

Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2003.02.063 ◽

2003 ◽

Vol 21 (6) ◽

pp. 976-983 ◽

Cited By ~ 939

Author(s):

I. Craig Henderson ◽

Donald A. Berry ◽

George D. Demetri ◽

Constance T. Cirrincione ◽

Lori J. Goldstein ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Estrogen Receptor ◽

Adjuvant Chemotherapy ◽

Confidence Interval ◽

Chemotherapy Regimen ◽

Disease Free Survival ◽

Free Survival ◽

Adjuvant Chemotherapy Regimen ◽

Disease Free

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

Download Full-text

Role of adjuvant therapy in stage IIIC2 endometrial cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001446 ◽

2020 ◽

Vol 30 (8) ◽

pp. 1169-1176

Author(s):

Giorgio Bogani ◽

Serena Cappuccio ◽

Jvan Casarin ◽

Deepa Maheswari M Narasimhulu ◽

William A Cilby ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Adjuvant Therapy ◽

External Beam Radiotherapy ◽

Disease Free Survival ◽

External Beam ◽

Free Survival ◽

Radiotherapy Alone ◽

Node Metastases ◽

Disease Free

ObjectiveThe role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant therapy in patients with stage IIIC2 endometrial cancer.MethodsThis retrospective single-institution study assessed patients with stage IIIC2 endometrial cancer who underwent primary surgery from January 1984 to December 2014. All patients had hysterectomy (±salpingo-oophorectomy) plus lymphadenectomy (para-aortic nodes, ±pelvic nodes). We included all patients with stage III endometrial cancer and documented para-aortic lymph node metastases (International Federation of Obstetrics and Gynecologists stage IIIC2). We excluded patients who did not provide consent, who had synchronous cancer, or who underwent neoadjuvant chemotherapy. Follow-up was restricted to the first 5 years post-operatively. Cox proportional hazards models, with age as the time scale, was used to evaluate associations of risk factors with disease-free survival and overall survival.ResultsAmong 105 patients with documented adjuvant therapy, external beam radiotherapy was administered to 25 patients (24%), chemotherapy to 24 (23%), and a combination (chemotherapy and external beam radiotherapy) to 56 (53%) patients. Most patients receiving chemotherapy and external beam radiotherapy (80%) had chemotherapy first. The majority of relapses had a distant component (31/46, 67%) and only one patient had an isolated para-aortic recurrence. Non-endometrioid subtypes had poorer disease-free survival (HR 2.57; 95% CI 1.38 to 4.78) and poorer overall survival (HR 2.00; 95% CI 1.09 to 3.65) compared with endometrioid. Among patients with endometrioid histology (n=60), chemotherapy and external beam radiotherapy improved disease-free survival (HR 0.22; 95% CI 0.07 to 0.71) and overall survival (HR 0.28; 95% CI 0.09 to 0.89) compared with chemotherapy or external beam radiotherapy alone. Combination therapy did not improve prognosis for patients with non-endometrioid histology (n=45).ConclusionsIn our cohort of patients with stage IIIC2 endometrioid endometrial cancer, those receiving chemotherapy and external beam radiotherapy had improved survival compared with patients receiving chemotherapy or external beam radiotherapy alone. However, the prognosis of patients with non-endometrioid endometrial cancer remained poor, regardless of the adjuvant therapy administered. Distant recurrences were the most common sites of failure.

Download Full-text

Stage IB Endometrioid Type Endometrial Cancer: The Role of Lymphadenectomy and Adjuvant Radiation Therapy

Gynecology Obstetrics and Reproductive Medicine ◽

10.21613/gorm.2017.704 ◽

2018 ◽

Vol 24 (3) ◽

pp. 156

Author(s):

Osman Turkmen ◽

Tolga Tasci ◽

Derman Basaran ◽

Gunsu Comert Kimyon ◽

Alper Karalök ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Adjuvant Radiotherapy ◽

Survival Rates ◽

Disease Free Survival ◽

Adjuvant Radiation ◽

Free Survival ◽

Stage Ib ◽

Gynecology And Obstetrics ◽

Disease Free

Objective: Both performances of lymphadenectomy and benefit of adding adjuvant radiotherapy are controversial for patients with International Federation of Gynecology and Obstetrics stage IB endometrioid type endometrial cancer. We aimed to identify the role of lymphadenectomy and adjuvant radiation therapy as well as clinicopathological prognostic factors for this group of patients. Study Design: Records of all patients (n=132) with stage IB endometrioid endometrial cancer who were referred to or treated in our institution between Jan 1992 and Dec 2013 were retrospectively reviewed. Cox Proportional Hazard Regression Analysis was used to determine the effects of lymphadenectomy and adjuvant radiation as well as other clinicopathological factors on disease free survival and overall survival.Results: Mean age was 59.9 years (range, 45-82). Lymphadenectomy didn't perform in 36 (27.3%) patients and 23 (17.4%) patients did not have any kind of adjuvant treatment. Mean lymph node count was 18.8 (range, 3-67). Federation of Gynecology and Obstetrics grade, lymphovascular space invasion, lymphadenectomy, receiving adjuvant treatment and type of received adjuvant therapy were not associated with disease free survival and overall survival for the entire cohort. In a subgroup of patients with grade1&2 tumor, 5-year disease free survival rates were 80% and 50% (p=0.4), respectively and overall survival rates were 94.8% and 93.8% (p=0.2), respectively for patients who had or didn't have adjuvant radiotherapy. While performance of lymphadenectomy was not significantly associated with disease free survival in this subgroup (p=0.56), this association was statistically significant for overall survival (97.9% vs. 86.4%, p=0.04) Conclusion: Benefit of adjuvant radiotherapy in regard to prevention of recurrence needs to be confirmed by further studies. Lymphadenectomy had a survival benefit for patients with myometrial invasion greater than a half of myometrial thickness.

Download Full-text