Lymph Node Metastases
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2021 ◽  
Vol 67 (3) ◽  
pp. 107-112
Livia Petrusel ◽  
Maria Ilies ◽  
Daniel Leucuta ◽  
Ioana Rusu ◽  
Andrada Seicean ◽  

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

Oral Oncology ◽  
2021 ◽  
Vol 123 ◽  
pp. 105627
Oisín Bugter ◽  
Yassine Aaboubout ◽  
Mahesh Algoe ◽  
Henriëtte S. de Bruijn ◽  
Stijn Keereweer ◽  

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5876
Konstantinos S. Papadakos ◽  
Catharina Hagerling ◽  
Lisa Rydén ◽  
Anna-Maria Larsson ◽  
Anna M. Blom

Cartilage oligomeric matrix protein (COMP) is a regulator of the extracellular matrix and is expressed primarily in the cartilage. Recently, COMP expression was also documented in breast cancer patients both in sera and tumor biopsies, in both of which it could serve as an independent prognostic marker. This study aimed to assess COMP as a potential biomarker in the group of metastatic breast cancer patients. Levels of COMP were measured by ELISA in serum samples of 141 metastatic breast cancer patients. Biopsies from primary tumors, synchronous lymph node metastases, and distant metastases were stained for COMP expression. The levels of serum COMP were higher in patients with ER- and HER2-positive tumors when compared to triple-negative tumors and correlated with the presence of bone and lung metastases, circulating tumor cell count, and clusters. Most of the primary tumors expressing COMP (70%) retained the expression also in the lymph node metastases, which correlated with visceral metastases and reduced survival. In conclusion, COMP appears as a valuable biomarker in metastatic breast cancer patients indicating a more severe stage of the disease. Serum COMP levels were associated with specific types of metastases in patients with metastatic breast cancer emphasizing that further studies are warranted to elucidate its potential role as a monitoring marker.

2021 ◽  
Liuhua Zhou ◽  
Qiaodan Zhu ◽  
Jincao Yao ◽  
Chen Yang ◽  
Dong Xu

Abstract Background Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma, and is prone to cervical lymph node metastases (CLNM). We aim to analyze the correlation between clinical information, ultrasonic parameters of PTC and CLNM. Methods 1335 patients who had pathologically confirmed unifocal PTC were enrolled. Univariate and multivariate logistic analysis were performed to predict CLNM in PTC patients. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance. Results Univariate analysis showed that gender, age, maximum tumor diameter and volume, cross-sectional and longitudinal aspect ratio were related to CLNM (P<0.05). Multivariate logistic analysis showed that gender, age, maximum tumor diameter and volume were independent correlative factors, cross-sectional aspect ratio had significant difference for PTC2 to predict CLNM. The area under the curve (AUC) of the maximum tumor diameter and volume was 0.738 and 0.733, respectively. Maximum tumor diameter and volume, and cross-sectional and longitudinal aspect ratio were statistically significant following analysis of variance (P < 0.05). Conclusions Younger age, male, and larger tumor were high risk factors for CLNM in patients with unifocal PTC. Cross-sectional aspect ratio had a more effective predictive value for CLNM in patients with larger thyroid tumors.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Zeng Fang ◽  
Ruizhi Wang ◽  
Ciqiu Yang ◽  
Dong Wang ◽  
Wanna Chen ◽  

Background. We developed a new nomogram combining serum biomarkers with clinicopathological features to improve the accuracy of prediction of nonsentinel lymph node (SLN) metastases in Chinese breast cancer patients. Methods. We enrolled 209 patients with breast cancer who underwent SLN biopsy and axillary lymph node dissection. We evaluated the relationships between non-SLN metastases and clinicopathologic features, as well as preoperative routine tests of blood indexes, tumor markers, and serum lipids, including lipoprotein a (Lp(a)). Risk factors for non-SLN metastases were identified by logistic regression analysis. The nomogram was created using the R program to predict the risk of non-SLN metastases in the training set. Receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in the validation set. Results. Lp(a) was significantly associated with non-SLN metastasis status. Compared with the MSKCC model, the predictive ability of our new nomogram that combined Lp(a) level and clinical variables (pathologic tumor size, lymphovascular invasion, multifocality, and positive/negative SLN numbers) was significantly greater (AUC: 0.732, 95% CI: 0.643–0.821) (C-index: 0.703, 95% CI: 0.656–0.791) in the training cohorts and also performed well in the validation cohorts (C-index: 0.773, 95% CI: 0.681–0.865). Moreover, the new nomogram with Lp(a) improved the accuracy (12.10%) of identification of patients with non-SLN metastases (NRI: 0.121; 95% CI: 0.081–0.202; P = 0.011 ). Conclusions. This novel nomogram based on preoperative serum indexes combined with clinicopathologic features facilitates accurate prediction of risk of non-SLN metastases in Chinese patients with breast cancer.

2021 ◽  
Vol 23 (3) ◽  
pp. 466-469
Viktoriia A. Amosova ◽  
Aleksandr V. Petrovskii ◽  
Marina S. Karpova ◽  
Nataliia V. Ponedel’nikova ◽  
Mona A. Frolova

Data analysis showed that many diagnostic issues in breast cancer patients with skin involvement are not systematized. In some cases when the tumor is small and skin involvement symptoms are minimal ("local" skin edema), should this category of patients be considered as patients with non-inflammatory skin involvement breast cancer? Current research confirms the presence of skin involvement has much less prognostic value than, for example, tumor size or lymph node metastases, and the surgical term "unresectable" may not always be adequate. In addition, clinical data often do not correspond to pathological data, which also complicates the staging and leads to "overtreatment" of such patients. Thus, further research is needed to identify categories of breast cancer (patients with skin involvement similar in prognosis, as well as to individualize approaches to local and systemic treatment.

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5763
Christian Doll ◽  
Carolin Bestendonk ◽  
Kilian Kreutzer ◽  
Konrad Neumann ◽  
Anne Pohrt ◽  

Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

2021 ◽  
Vijay S

Abstract Breast cancer is the most common cancer found in women. 1. Metastasis is the leading cause of mortality among cancer patients. 2. As the number of axillary lymph nodes with metastases grows the prognosis for patients with breast cancer worsens3. We used a published microarray dataset4 to find genes linked to lymph node metastasis, which is an early stage of breast cancer metastasis. When comparing original breast tumors to lymph node metastases from patients diagnosed with breast cancer, we discovered substantial differences in LHFP gene expression. When comparing primary breast tumors to neighboring normal breast tissue, LHFP was shown to be one of the most differentially expressed genes in a separate microarray dataset5. In individuals with breast cancer, LHFP expression was shown to be substantially linked with median overall survival. LHFP may be involved in the mechanisms that lead to the transformation or progression of the original tumor in human breast cancer, as well as lymph node metastasis. Breast cancer, breast cancer metastasis, lymph node metastasis, LHFP, breast cancer systems biology, and breast cancer targeted treatments.

2021 ◽  
Vol 13 (1) ◽  
Christoph Röcken ◽  
Anu Amallraja ◽  
Christine Halske ◽  
Luka Opasic ◽  
Arne Traulsen ◽  

Abstract Background Cancer is a somatic evolutionary disease and adenocarcinomas of the stomach and gastroesophageal junction (GC) may serve as a two-dimensional model of cancer expansion, in which tumor subclones are not evenly mixed during tumor progression but rather spatially separated and diversified. We hypothesize that precision medicine efforts are compromised when clinical decisions are based on a single-sample analysis, which ignores the mechanisms of cancer evolution and resulting intratumoral heterogeneity. Using multiregional whole-exome sequencing, we investigated the effect of somatic evolution on intratumoral heterogeneity aiming to shed light on the evolutionary biology of GC. Methods The study comprised a prospective discovery cohort of 9 and a validation cohort of 463 GCs. Multiregional whole-exome sequencing was performed using samples form 45 primary tumors and 3 lymph node metastases (range 3–10 tumor samples/patient) of the discovery cohort. Results In total, the discovery cohort harbored 16,537 non-synonymous mutations. Intratumoral heterogeneity of somatic mutations and copy number variants were present in all tumors of the discovery cohort. Of the non-synonymous mutations, 53–91% were not present in each patient’s sample; 399 genes harbored 2–4 different non-synonymous mutations in the same patient; 175 genes showed copy number variations, the majority being heterogeneous, including CD274 (PD-L1). Multi-sample tree-based analyses provided evidence for branched evolution being most complex in a microsatellite instable GC. The analysis of the mode of evolution showed a high degree of heterogeneity in deviation from neutrality within each tumor. We found evidence of parallel evolution and evolutionary trajectories: different mutations of SMAD4 aligned with different subclones and were found only in TP53 mutant GCs. Conclusions Neutral and non-neutral somatic evolution shape the mutational landscape in GC along its lateral expansions. It leads to complex spatial intratumoral heterogeneity, where lymph node metastases may stem from different areas of the primary tumor, synchronously. Our findings may have profound effects on future patient management. They illustrate the risk of mis-interpreting tumor genetics based on single-sample analysis and open new avenues for an evolutionary classification of GC, i.e., the discovery of distinct evolutionary trajectories which can be utilized for precision medicine.

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