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1.
Cancers (Basel) ; 15(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38136438

RESUMO

BACKGROUND: Recently, sentinel lymph node biopsy (SLNB) has been introduced in the surgical staging of endometrial cancer as an alternative to systematic lymph node dissection (LND). However, the survival impact of SLNB is not yet well characterised. METHODS: We performed a retrospective study of 419 patients with endometrial cancer treated with SLNB alone or with pelvic and para-aortic LND. For SLNB mapping, indocyanine green was used. RESULTS: Median follow-up was 66 months. After exclusions, 337 patients were eligible for analysis. Of them, 150 underwent SLNB and 187 LND. During the follow-up time, 27 (24.7%) of the 150 who underwent SLNB and 54 (28.9%) of the 187 who underwent LND were diagnosed with recurrent disease (p = 0.459). The estimated 5-year disease-free survival (DFS) rate was 76.7% and 72.2% for patients in the SLNB and LND group, respectively (p = 0.419). The 5-year overall survival (OS) rates were 80.7% and 77.0% in the SLNB and LND group, respectively (p = 0.895). Survival rates were similar in both groups independent of lymph node status. Multivariable analysis confirmed that the staging approach was not associated with oncological outcome. For patients without lymph node metastases, patient outcome was worsened by advanced tumour stage and non-endometrioid tumour histology. In the group of patients with confirmed lymph node metastases, advanced tumour stage and inadequate adjuvant treatment significantly reduced DFS and OS. CONCLUSION: Our data suggested that SLNB did not compromise the oncological outcome of patients with endometrial cancer compared to LND.

2.
Int J Mol Sci ; 24(22)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38003279

RESUMO

The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19-/-, BMyD88-/- and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19-/-, BMyD88-/- and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB.


Assuntos
Placenta , Nascimento Prematuro , Recém-Nascido , Humanos , Gravidez , Feminino , Animais , Camundongos , Placenta/metabolismo , Lipopolissacarídeos/efeitos adversos , Nascimento Prematuro/metabolismo , Inflamação/metabolismo , Feto/metabolismo
3.
Cancers (Basel) ; 15(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37686555

RESUMO

Ovarian cancer has the highest mortality rate among female reproductive tract malignancies. A complex network, including the interaction between tumor and immune cells, regulates the tumor microenvironment, survival, and growth. The role of mast cells (MCs) in ovarian tumor pathophysiology is poorly understood. We aimed to understand the effect of MCs on tumor cell migration and growth using in vitro and in vivo approaches. Wound healing assays using human tumor cell lines (SK-OV-3, OVCAR-3) and human MCs (HMC-1) were conducted. Murine ID8 tumor cells were injected into C57BL6/J wildtype (WT) and MC-deficient C57BL/6-KitW-sh/W-sh (KitW-sh) mice. Reconstitution of KitW-sh was performed by the transfer of WT bone marrow-derived MCs (BMMCs). Tumor development was recorded by high-frequency ultrasonography. In vitro, we observed a diminished migration of human ovarian tumor cells upon direct or indirect MC contact. In vivo, application of ID8 cells into KitW-sh mice resulted in significantly increased tumor growth compared to C57BL6/J mice. Injection of BMMCs into KitW-sh mice reconstituted MCs and restored tumor growth. Our data show that MCs have a suppressive effect on ovarian tumor growth and may serve as a new therapeutic target.

4.
Pneumologie ; 77(8): 461-543, 2023 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-37406667

RESUMO

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.


Assuntos
Antiasmáticos , Asma , Feminino , Gravidez , Humanos , Óxido Nítrico , Asma/terapia , Asma/tratamento farmacológico , Antiasmáticos/uso terapêutico , Biomarcadores , Dessensibilização Imunológica
5.
Blood Coagul Fibrinolysis ; 34(4): 233-238, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37115963

RESUMO

ABSTRACT: Exposure to higher levels of steroid hormones, like that in pregnancy or during combined hormonal contraception, increases the risk of venous thromboembolism. Development of resistance to activated protein C (APC) thought to be the underlying pathomechanism of this prothrombotic state. This coagulation phenomena is largely to be explained by the hormone-induced impairment of the protein S/ tissue factor pathway inhibitor (TFPI) leading to a less efficient inactivation of factor Va and factor VIIIa by APC. APC resistance and decreased protein S/TFPI function were associated with the risk of first as well as recurrent venous thromboembolism. Preexisting disturbances in these pathways are likely to predispose to thrombosis during hormone exposure and can persist over years after the thrombosis event.Further studies are necessary to investigate the predictive value of forgoing APC resistance and decreased protein S/TFPI function or an excessive alteration in these parameters during hormone intake on the development of hormone-induced venous thromboembolism.


Assuntos
Resistência à Proteína C Ativada , Trombose , Tromboembolia Venosa , Feminino , Gravidez , Humanos , Proteína S/metabolismo , Tromboembolia Venosa/induzido quimicamente , Fatores de Risco , Fator V , Hormônios/efeitos adversos
6.
J Cancer Res Clin Oncol ; 149(2): 709-719, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36534272

RESUMO

PURPOSES: Young breast cancer patients aged 35 years and younger are a small group of women who tend to present at high-risk form of the disease. More analysis of the data on tumor characteristics, treatment, and survival is necessary to help improving treatment and outcome. METHODS: In this retrospective study, we compared the clinical and tumor characteristics, the treatments, and the survival of 257 women aged ≤ 35 years, with 6566 women aged 50-69 years. We used a registry-based data of patients with invasive, non-metastatic breast cancer diagnosed between 2000 and 2015. RESULTS: Young women showed lower rate of hormone receptor (HR) positivity. Their tumors were more often HER2-positive, which showed lower rate of differentiation and higher rate of Ki-67 expression compared to their older counterparts. Women aged 35 years and younger were more likely to undergo neoadjuvant therapy and mastectomy. Endocrine therapy was underrepresented in young patients. 5-Year disease-free survival (DFS) was significantly lower in the younger patient group (81.7% vs. 91.3%, p < 0.001), while 5-year overall survival (OS) was not impaired (91.4% vs. 91.1%, p = 0.847). CONCLUSION: The unfavorable disease-free survival in the group of younger patients might be explained by their unfavorable tumor characteristics. The surgical treatment appears to be more aggressive in young breast cancer patients and is more frequently combined with chemotherapy and immunotherapy, either in a neoadjuvant or in an adjuvant setting.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Estudos Retrospectivos , Mastectomia , Prognóstico , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Arch Gynecol Obstet ; 307(5): 1573-1583, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36282347

RESUMO

BACKGROUND: Several international studies reported relatively high re-excision rates due to residual tumor in breast conserving surgery (BCS). Cavity shaving (CS) is a surgical strategy to reduce re-excision rates. This study aimed to investigate the effect of circumferential cavity shaving during BCS to reduce residual tumor. MATERIAL AND METHODS: A total of 591 patients with early invasive carcinoma or carcinoma in situ of the breast (ICD-10, C50 or D05) who were diagnosed between 01/01/2017 and 31/12/2019 and underwent BCS in a certified breast cancer center of the University Regensburg were analyzed regarding surgical excision methods. Patients with CS during BCS and patients with targeted re-excision in a specific direction depending on the result of intraoperative mammography or sonography during BCS were compared. The risk of pathologic residual tumor (R1) was compared between both groups by means of a multivariable binary logistic regression model to determine if there is a benefit of a certain surgical method to avoid a second intervention for re-excision. We adjusted for age, tumor size, nodal status, histologic type, surgeon, breast side, and neoadjuvant chemotherapy. RESULTS: 80 (n = 13.54%) patients had CS and 511 (n = 86.46%) had a targeted re-excision in a specific direction during BCS according to intraoperative mammography or sonography. After comparing both techniques in a multivariable regression model, there was no significant difference regarding risk of residual tumor (p = 0.738) in the total cohort. However, CS showed a tendency to be favorable regarding rates of residual tumor in patients with invasive breast cancer between 60 and 70 years (p = 0.072) and smaller T1-tumors (p = 0.057) compared to targeted intraoperative re-excision following mammographic or sonographic assessment. CONCLUSION: CS showed a tendency to reduce residual tumor compared to the standard technique of intraoperative re-excision in specific subgroups, although no statistical significance was reached. Further studies are needed to overcome potential limitations like surgeon-based bias and missing standardized definitions of CS to reduce residual tumor rates.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Carcinoma Ductal de Mama , Humanos , Feminino , Mastectomia Segmentar/métodos , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Neoplasia Residual/patologia , Reoperação , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Carcinoma in Situ/cirurgia , Estudos Retrospectivos
8.
J Cancer Res Clin Oncol ; 149(2): 803-810, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35179644

RESUMO

BACKGROUND: To date, information on risk factors and temporal patterns of recurrences in patients with vulvar cancer is sparse. Conclusive data for an optimal surveillance strategy are lacking. METHODS: This multicenter, retrospective population-based register study included 1412 patients who have been treated from 2000 to 2017 for vulvar cancer in the German districts of Upper Palatinate, Lower Bavaria, and Saxony-Anhalt. Kaplan-Meier method, and univariate and multivariate Cox regression were employed to evaluate prognostic factors and temporal course of overall survival, cumulative recurrence, and recurrence-free survival rates. RESULTS: After exclusion, the final study cohort comprised 829 patients. Most recurrences occurred within the first 3 years after diagnosis. Notably, a significant subset of patients were recurrent even after 5 years. The cumulative recurrence rate from all relapses was 18.6% 1 year after primary diagnosis. The recurrence rate increased to 34.7% after 3, to 41.8% after 5, and to 56.6% after 10 years post-diagnosis. The risk of relapse was significantly increased in patients over 70 years of age (hazard ratio (HR) = 2.7; p < 0.001; 95% CI 1.6-4.4), and in patients with positive nodal status N1 (HR = 2.0; p = 0.019; 95% CI 1.1-3.5) and N2/3 (HR = 2.2; p = 0.033; 95% CI 1.1-4.4). CONCLUSION: Our study provides compelling evidence that follow-up care should be carried out for longer than 5 years, especially for high-risk patients.


Assuntos
Neoplasias Vulvares , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Seguimentos , Neoplasias Vulvares/terapia , Recidiva Local de Neoplasia/epidemiologia , Fatores de Risco
10.
Gynecol Oncol ; 166(1): 57-60, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35618539

RESUMO

OBJECTIVE: The aim of this study was to investigate the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. METHODS: In this population-based cohort study we analysed from clinical cancer registries to determine DFS of women with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB1 cervical cancer with respect to conization preceding radical hysterectomy performed between January 2010 and December 2015. RESULTS: Out of 993 datasets available for the analysis, 235 patients met the inclusion criteria of the current study. The median follow-up was 5.4 years. During the study period, 28 (11.9%) recurrences were observed. All of these occurred in patients with FIGO stage IB1. For further evaluation, patients with FIGO IB1 tumors <2 cm were further analysed and divided into two groups, based on pre-operative conization. Pre-operative conization was associated with a reduced rate of recurrence (p = 0.007), with only three (5.2%) recurrences in this group (CO) compared to 25 recurrences (21.0%) in the group without conization (NCO) preceding radical hysterectomy. DFS was estimated at 79.0% and 94.8% in NCO and CO, respectively (p = 0.008). After adjustment for other prognostic covariates, conization remained a favourable prognostic factor for DFS (HR 0.27; 95% CI 0.08-0.93, p = 0.037). Lymph node involvement was the only unfavourable factor (HR 4.38; 95% CI 1.36-14.14, p = 0.014) in the multivariable analysis. CONCLUSIONS: Pre-operative conization is associated with improved DFS in early-stage cervical cancer independently of the surgical approach.


Assuntos
Conização , Neoplasias do Colo do Útero , Estudos de Coortes , Conização/métodos , Feminino , Humanos , Estadiamento de Neoplasias , Gravidez , Recidiva , Neoplasias do Colo do Útero/patologia
11.
Cancer Invest ; 40(7): 621-628, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35435097

RESUMO

We investigated the survival effect of lymphadenectomy in ovarian cancer. The five-year progression-free and overall survival in early-stage ovarian cancer were not affected. Preliminary, unadjusted analysis in advanced ovarian cancer suggested an improvement in survival. However, after adjusting for other factors, e.g. ECOG performance status and patients' age, this survival advantage vanished. Our analysis suggests that systemic pelvic and para-aortic lymphadenectomy was not associated with an improvement of the progression-free and overall survival of patients with optimally debulked ovarian cancer.


Assuntos
Excisão de Linfonodo , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Pelve/patologia , Estudos Retrospectivos
12.
J Cancer Res Clin Oncol ; 148(5): 1033-1043, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35122110

RESUMO

PURPOSE: We aimed to evaluate the role of the chorioallantoic membrane model (CAM) in breast cancer research. METHODS: The following is an overview of the use of the CAM in the field of breast cancer research based on a PubMed literature query. RESULTS: The CAM is a 3D in vivo model that can be used for the analysis of tumor growth, biology and angiogenesis of primary tumor tissue or tumor cell lines. The CAM model has been used in breast cancer research for drug testing, migration assays and the evaluation of vascularization, amongst others. The CAM model is a valuable method that offers a better imitation of the physiological phenomena compared to 2D or 3D in vitro models. CONCLUSION: The CAM model has primarily and successfully been utilized for the assessment of the tumor biology of established breast cancer cell lines. Further, the CAM model is a promising method to analyze patient derived primary tumor material and could be used as a "patient-specific 3D-tumor-therapy-model" for the cost-efficient evaluation of anti-cancer drugs to find the optimal treatment for breast cancer patients.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Corioalantoide/metabolismo , Membrana Corioalantoide/patologia , Feminino , Humanos , Neovascularização Patológica/patologia
13.
Cancers (Basel) ; 14(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35053582

RESUMO

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

14.
Virchows Arch ; 480(3): 529-541, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35020071

RESUMO

Patients with estrogen receptor positive breast cancer are usually receiving an anti-estrogen therapy by either aromatase inhibitors or selective estrogen receptor mediators such as tamoxifen. Nevertheless, acquired resistance to tamoxifen under treatment frequently hampers therapy. One proposed explanation for this phenomenon is the interaction of the tumor cells with cells of the tumor microenvironment via the Insulin-like growth factor RNA binding protein 5/B-cell lymphoma 3 (IGFBP5/BCL3) axis. Here we investigated whether a high expression of BCL3 either cytoplasmic or nuclear is associated with the occurrence of a relapse under anti-estrogen therapy in patients. Formaldehyde-fixed, paraffin-embedded samples of 180 breast cancer patients were analyzed for BCL3 expression by immunohistochemistry. An immunoreactive score (IRS) was calculated from staining intensity in cytoplasm and nucleus as well as the percentage of positive tumor cells. These scores were correlated with clinico-pathological parameters using cross-tabulation analysis and patients' relapse free and overall survival by Kaplan-Meier analysis and Cox regression. A tamoxifen-adapted MCF-7 derived cell line was investigated for BCL3 localization by immunofluorescence. The cytosolic BCL3-IRS significantly correlated with the proliferation marker Ki-67, and with the occurrence of a relapse under tamoxifen treatment. Nuclear score correlated only with tamoxifen-relapse. In survival analysis, both scores were highly significant prognostic factors for relapse free, but not for overall survival. This was especially obvious for estrogen receptor positive and HER2/NEU negative cases as well as lobular breast cancer. Tamoxifen-treated, but not aromatase-treated patients had a poor survival when BCL3 scores were high. A tamoxifen adapted cell line exhibited a reduced expression and mainly nuclear localization of BCL3, compared to the parental estrogen receptor positive cell-line MCF-7. Altogether, these data strongly support a function of BCL3 in tamoxifen resistance and its potential use as a predictive biomarker for tamoxifen resistance.


Assuntos
Neoplasias da Mama , Tamoxifeno , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Recidiva Local de Neoplasia , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Microambiente Tumoral
15.
Arch Gynecol Obstet ; 305(1): 203-213, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34223974

RESUMO

PURPOSE: Treatment according to guidelines has been demonstrated to improve survival in a number of different cancer entities. Deviations from guidelines depend on several factors, including the patient's preferences, age and comorbidities. The aim of this study was to assess the adherence to guideline recommendations concerning surgical and adjuvant treatment in endometrial cancer. Furthermore, we sought to evaluate the reasons for non-adherence to guidelines by further examining the influence of comorbidities and age. METHODS: The influence of age, comorbidities, tumor stage and histological subtype on guideline adherence was evaluated by multivariable logistic regression in a cohort of 353 high-grade endometrial cancer patients. High-grade endometrial cancer was defined as carcinosarcoma, Type II (serous, clear cell, mixed cell carcinoma) and Type I G3 histology. RESULTS: Extensive surgical procedures, particularly systematic LNE, were less frequently applied in patients with comorbidities (p = 0.015) or higher age (p < 0.01). Guideline adherence was not affected by comorbidities (p = 0.563), but was significantly reduced with higher age (p < 0.01). In a multivariable model, higher age (p < 0.01), obesity (p = 0.011), higher FIGO Stage (p < 0.01) and histologic subtype (p < 0.01) significantly decreased OS. Surgery (p < 0.001), chemotherapy (p < 0.01) and systematic LNE (p = 0.011) were associated with higher OS. CONCLUSION: Age seems to be the strongest independent factor leading to guideline deviation. Comorbidities were associated with less aggressive treatment, but not with deviations from guidelines.


Assuntos
Carcinossarcoma , Neoplasias do Endométrio , Carcinossarcoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos
16.
Gynecol Oncol ; 164(1): 68-75, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34794839

RESUMO

BACKGROUND: The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. PATIENTS AND METHODS: In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. RESULTS: The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). CONCLUSION: Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV- tumors.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Neoplasias Vulvares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia , Adulto Jovem
17.
Contemp Oncol (Pozn) ; 25(3): 204-212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729041

RESUMO

INTRODUCTION: The G protein-coupled oestrogen receptor 1 (GPER-1) is a potential prognostic marker in breast cancer. However, its role in male breast cancer (MBC) is still unknown. This study evaluates the expression of GPER-1 in MBC samples and correlates these data with clinical and pathological parameters including patients' survival. MATERIAL AND METHODS: For this retrospective analysis of a prospectively maintained cohort of patients with MBC, we examined 161 specimens for GPER-1 expression using immunohistochemistry. An immunoreactive score (IRS) was calculated based on staining intensity and the percentage of positive tumour cells. Then, we correlated GPER-1 IRS with clinical and pathological parameters, and overall and relapse-free survival. RESULTS: About 40% of MBC samples were positive for GPER-1 expression (IRS ≥ 4). There was no significant correlation with clinicopathological parameters, such as hormone receptor status or grading. However, a statistical trend was observed for tumour size (≥ 2 cm, p = 0.093). Kaplan-Meier survival analysis revealed no significant correlation with relapse-free survival. However, there was a significant correlation with overall survival, but when we adjusted the log-rank p-value to compensate for the cut-off point optimization method, it rose above 0.1. Additionally, GPER-1-positive patients were older at diagnosis. When adjusted for age by multivariable Cox regression analysis, the significance of GPER-1 status for survival was further reduced. CONCLUSIONS: We found no significant prognostic value of GPER-1 in this MBC cohort as anticipated from studies on female BC. Future studies with higher sample size are needed to further verify a potential sex-specific role of GPER-1.

19.
Cancer Biomark ; 32(2): 161-173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34092612

RESUMO

BACKGROUND: Neuronatin (NNAT) determined by immunohistochemistry is a negative prognostic biomarker for breast cancer, independent of the major clinicopathological markers. OBJECTIVE: Here, we investigated whether NNAT is also a predictive biomarker for pathological remission after neoadjuvant chemotherapy. METHODS: One hundred and four breast cancer patients, treated with systemic neoadjuvant chemotherapy were included in this retrospective study. NNAT was detected in formaldehyde fixed, paraffin embedded primary cancer tissue by immunohistochemistry and an immuno-reactive score (IRS) determined. Pathological remission was scored according to Sinn and by evaluation of cytopathic effects. NNAT-IRS was correlated with clinicopathological parameters as well as relapse free and overall survival and for pathological remission after neoadjuvant therapy. RESULTS: NNAT IRS was an independent prognostic marker for relapse free and overall survival and the time from diagnosis to the "tumor-free" state. NNAT IRS was associated with Luminal-A tumors and correlated slightly negative with age and lymph-node metastasis. There was no significant correlation of NNAT-IRS with Sinn's remission score, but with cytopathic effects of chemotherapy. CONCLUSIONS: We confirmed the prognostic impact of NNAT-IRS in an independent cohort of neoadjuvantly treated patients. Additionally, a correlation with a score for pathological remission under systemic neoadjuvant chemotherapy for breast cancer was found.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/mortalidade , Proteínas de Membrana/análise , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Proteínas do Tecido Nervoso/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Proteínas do Tecido Nervoso/metabolismo , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos
20.
Acta Oncol ; 60(7): 897-903, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33905297

RESUMO

BACKGROUND: Similarities in outcome between grade 3 endometrioid cancer and non-endometrioid histologies have been reported by a number of studies. Other reports, however, stated a significantly better prognosis for G3 endometrioid compared to type II histology. In this population-based study, we compared the outcome and treatment approaches of high-grade endometrial cancer patients with FIGO stages I-III depending on their histology. MATERIAL AND METHODS: 284 high-grade endometrial cancer patients diagnosed between 1998 and 2015 were retrospectively analyzed. Overall survival (OS), recurrence-free survival (RFS), and recurrence rates were compared depending on histology. RESULTS: Type I G3 patients had a statistically significant OS advantage over women suffering from type II carcinoma (HR 1.527, 95%-CI 1.024-2.276; p = 0.038) and carcinosarcoma (HR 2.106, 95%-CI 1.270-3.493; p = 0.004) in univariable and multivariable Cox-regression analysis. RFS in Type I G3 was significantly superior compared to patients with carcinosarcoma (HR 1.719, 95%-CI 1.018-2.901; p = 0.043) and not significantly superior to type II patients (HR 1.368, 95%-CI 0.920-2.036; p = 0.122). Cumulative recurrence rates were significantly higher in carcinosarcoma compared to type I G3 (HR 2.217, 95%-CI 1.096-4.485; p = 0.027) in univariable analysis, but not after risk adjustment (HR of 1.472, 95%-CI 0.654-3.311; p = 0.350). CONCLUSION: The prognosis of patients with type I G3 endometrial cancer patients seems to be significantly superior to patients with type II cancer and particularly carcinosarcoma. Systematic LND seemed to be beneficial in all of the three subtypes. The benefit of adjuvant treatment methods may differ between histologies.


Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
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