Rare basal cell metastasis of a basal-squamous skin collision tumour to the lung and axillary lymph node.
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ABSTRACT:
SUBMITTER: Li R
PROVIDER: S-EPMC6782041 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Oral squamous cell carcinomas (OSCCs) are genetically heterogeneous and exhibit diverse stromal and immune microenvironments. Acquired resistance to standard chemo-, radio-, and targeted therapies remains a major hurdle in planning effective treatment modalities for OSCC patients. Since Caspase 8 (CASP8) is frequently mutated in OSCCs, we were interested to explore a potential interaction between tumour-infiltrating lymphocytes (TILs) and CASP8 activation using high-content image analysis of human tumour (n = 32) sections. Despite the lymphocyte-rich tumour microenvironment, we observed lower activation of CASP8 (0-10% of tumour area) and its downstream effector CASP3 (0-6%) in tumours than in normal oral epithelium. Conversely, we found apoptosis was high for all the lymphocyte subtypes examined (38-52% of lymphocytes within tumour islands). Tumours with higher Fas ligand (FasL) expression had a significantly higher proportion of cleaved CASP3/8 positive cytotoxic T cells within the tumour islands (p = 0.05), and this was associated with the presence of lymph node metastatic disease [odds ratio: 1.046, 95% confidence interval (1.002-1.091), p = 0.039]. Our finding of extensive activation of the extrinsic pathway of apoptosis in TILs, together with evidence of higher FasL in CASP8 mutated tumours, may be useful in predicting the course of disease in individual patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
| S-EPMC10772935 | biostudies-literature
Project description:Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51-68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41-0.74 and 0.48-0.89 in the training cohorts, respectively, and between 0.30-0.98 and 0.37-0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.
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Project description:ObjectivesTo determine whether ultrasound radiomics can be used to distinguish axillary lymph nodes (ALN) metastases in breast cancer based on ALN imaging.MethodsA total of 147 breast cancer patients with 41 non-metastatic lymph nodes and 109 metastatic lymph nodes were divided into a training set (105 ALN) and a validation set (45 ALN). Radiomics features were extracted from ultrasound images and a radiomics signature (RS) was built. The Intraclass correlation coefficients (ICCs), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) methods were used to select the ALN status-related features. All images were assessed by two radiologists with at least 10 years of experience in ALN ultrasound examination. The performance levels of the model and radiologists in the training and validation subgroups were then evaluated and compared.ResultRadiomics signature accurately predicted the ALN status, achieved an area under the receiver operator characteristic curve of 0.929 (95%CI, 0.881-0.978) and area under curve(AUC) of 0.919 (95%CI, 95%CI, 0.841-0.997) in training and validation cohorts respectively. The radiomics model performed better than two experts' prediction of ALN status in both cohorts (P<0.05). Besides, prediction in subgroups based on baseline clinicopathological information also achieved good discrimination performance, with an AUC of 0.937, 0.918, 0.885, 0.930, and 0.913 in HR+/HER2-, HER2+, triple-negative, tumor sized ≤ 3cm and tumor sized>3 cm, respectively.ConclusionThe radiomics model demonstrated a good ability to predict ALN status in patients with breast cancer, which might provide essential information for decision-making.
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Project description:Focal adhesion kinase (p125(FAK); 'FAK') is a tyrosine kinase that is localised to cellular focal adhesions and is associated with a number of other proteins, such as integrin adhesion receptors. We performed an immunohistochemical analysis of FAK protein expression to determine the relationship between FAK overexpression and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 91 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Seven human ESCC cell lines-TE-1, TE-2, TE-8, TE-13, TE-15, TT, and TTn-and one immortalized human keratinocyte cell line-HaCaT-were used in Western blot analysis. Immunostaining of FAK was seen in the cytoplasm of cancer cells, particularly in cells located in the invasive fronts of cancer nests. FAK overexpression was detected in 54 of the 91 patients (59.3%). Significant correlations were observed between FAK overexpression and cell differentiation (P=0.0057), depth of tumour invasion (P=0.0023), presence of regional lymph node metastasis (P=0.0097), number of lymph node metastases (P=0.0026), and disease stage (P=0.012). The survival rates of patients with FAK-overexpressing cancer were significantly lower than those of patients without FAK-overexpression cancer (P=0.006). The 5-year survival rate of patients without FAK overexpression was 69%, whereas that of patients with FAK overexpression was 38%. On Western blot analysis, FAK was expressed at a high level in TE-1, TE-8, TE-15, and TT cells, at a moderate level in TE-2 and TTn cells, and at a low level in TE13 and HaCaT cells. FAK phosphorylation at tyrosine 397 was demonstrated in proportion to the intensity of FAK in all cell lines except TE15 and HaCaT. In conclusion, FAK overexpression of ESCC was related to cell differentiation, tumour invasiveness, and lymph node metastasis. Consequently, patients with ESCC who had FAK overexpression had a poor prognosis.
| S-EPMC2394235 | biostudies-other
Project description:This study aimed to develop and validate a deep learning radiomics nomogram (DLRN) for the preoperative evaluation of axillary lymph node (ALN) metastasis status in patients with a newly diagnosed unifocal breast cancer. A total of 883 eligible patients with breast cancer who underwent preoperative breast and axillary ultrasound were retrospectively enrolled between April 1, 2016, and June 30, 2022. The training cohort comprised 621 patients from Hospital I; the external validation cohorts comprised 112, 87, and 63 patients from Hospitals II, III, and IV, respectively. A DLR signature was created based on the deep learning and handcrafted features, and the DLRN was then developed based on the signature and four independent clinical parameters. The DLRN exhibited good performance, yielding areas under the receiver operating characteristic curve (AUC) of 0.914, 0.929, and 0.952 in the three external validation cohorts, respectively. Decision curve and calibration curve analyses demonstrated the favorable clinical value and calibration of the nomogram. In addition, the DLRN outperformed five experienced radiologists in all cohorts. This has the potential to guide appropriate management of the axilla in patients with breast cancer, including avoiding overtreatment.
| S-EPMC10933422 | biostudies-literature
Project description:ObjectivesThe goal of this study was to assess the clinicopathological and ultrasound (US) features of breast cancer for predicting the risk of axillary lymph node metastasis.MethodsPatients with breast cancer were included in this retrospective, monocentric, observational study. Their preoperative ultrasound features, clinical data, laboratory results and postoperative pathologic results and immunophenotyping were collected. The association of these factors of breast cancer with axillary lymph node metastasis was evaluated by univariate and multivariate analysis.ResultsIn this study, 471 patients diagnosed with breast cancer at the First Affiliated Hospital of Xi'an Jiaotong University between July 2016 and September 2019 were collected, with a total of 471 nodules, of which 231(49.0%) had axillary lymph node metastasis, and 240(51.0%) did not. The parameters of hyperechoic halo, posterior acoustic decrease, microcalcification, carcinogenic embryonic antigen (CEA), cancer antigen-153 (CA153), CK5/6 (+), Ki67 (≥40%), AR (+) and histological grade (grade II and grade III) were significantly and independently associated with axillary lymph node metastasis (p < 0.05 for all).ConclusionsThe combination of ultrasound features, tumor markers, pathology, and immunohistochemistry can predict axillary lymph node metastasis in breast cancer patients.
| S-EPMC10657709 | biostudies-literature
Project description:Metastasis is a multistep process that is not well understood. Colonization of a secondary organ requires specific molecular alterations of the host microenvironment. To determine the temporal and spatial changes associated with metastatic dissemination to the axillary lymph nodes, gene expression profiles were compared between histologically normal lymph nodes from node-positive patients and tumor-free nodes from node-negative patients. Using a stringent false discovery rate correction (<0.05) for multiple hypothesis testing, we did not detect any differentially expressed genes between the lymph node groups. Thus, the presence of metastatic cells within the lymphatic system does not elicit widespread changes in gene expression through the axillary basin; rather, lymph nodes independently respond to disseminated tumor cells.
| S-EPMC5391061 | biostudies-literature
Project description:It is difficult to accurately assess axillary lymph nodes metastasis and the diagnosis of axillary lymph nodes in patients with breast cancer is invasive and has low-sensitivity preoperatively. This study aims to develop a mammography-based radiomics nomogram for the preoperative prediction of ALN metastasis in patients with breast cancer. This study enrolled 147 patients with clinicopathologically confirmed breast cancer and preoperative mammography. Features were extracted from each patient's mammography images. The least absolute shrinkage and selection operator regression method was used to select features and build a signature in the primary cohort. The performance of the signature was assessed using support vector machines. We developed a nomogram by incorporating the signature with the clinicopathologic risk factors. The nomogram performance was estimated by its calibration ability in the primary and validation cohorts. The signature was consisted of 10 selected ALN-status-related features. The AUC of the signature from the primary cohort was 0.895 (95% CI, 0.887-0.909) and 0.875 (95% CI, 0.698-0.891) for the validation cohort. The C-Index of the nomogram from the primary cohort was 0.779 (95% CI, 0.752-0.793) and 0.809 (95% CI, 0.794-0.833) for the validation cohort. Our nomogram is a reliable and non-invasive tool for preoperative prediction of ALN status and can be used to optimize current treatment strategy for breast cancer patients.
| S-EPMC6418289 | biostudies-literature
Project description:Among patients with a preoperative positive axillary ultrasound, around 40% of them are pathologically proved to be free from axillary lymph node (ALN) metastasis. We aimed to develop and validate a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. Clinicopathological features of 322 early breast cancer patients with positive axillary ultrasound findings were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of ALN metastasis. A model was created from the logistic regression analysis, comprising lymph node transverse diameter, cortex thickness, hilum status, clinical tumour size, histological grade and estrogen receptor, and it was subsequently validated in another 234 patients. Coefficient of determination (R(2)) and the area under the ROC curve (AUC) were calculated to be 0.9375 and 0.864, showing good calibration and discrimination of the model, respectively. The false-negative rates of the model were 0% and 5.3% for the predicted probability cut-off points of 7.1% and 13.8%, respectively. This means that omission of axillary surgery may be safe for patients with a predictive probability of less than 13.8%. After further validation in clinical practice, this model may support increasingly limited surgical approaches to the axilla in breast cancer.
| S-EPMC4753408 | biostudies-other
Project description:PurposeThe purpose of this study was to distinguish axillary lymph node (ALN) status using preoperative breast DCE-MRI radiomics and compare the effects of two-dimensional (2D) and three-dimensional (3D) analysis.MethodsA retrospective study including 154 breast cancer patients all confirmed by pathology; 80 with ALN metastasis and 74 without. All MRI scans were achieved at a 3.0 Tesla scanner with 7 post-contrast MR phases sequentially acquired with a temporal resolution of 60 s. MRI radiomic features were extracted separately from a 2D single slice (i.e., the representative slice) and the 3D tumor volume. Several machine learning classifiers were built and compared using 2D or 3D analysis to distinguish positive vs negative ALN status. We performed independent test and 10-fold cross validation with multiple repetitions, and used bootstrap test, least absolute shrinkage selection operator, and receiver operating characteristic (ROC) curve analysis as statistical tests.ResultsThe highest area under the ROC curve (AUC) was 0.81 (95% confidence intervals [CI]: 0.80-0.83) and 0.82 (95% CI: 0.81-0.82) for 2D and 3D analysis, respectively; the corresponding accuracy was 79% and 80%. The linear discriminant analysis (LDA) classifier achieved the highest classification performance. None of the AUC differences between 2D and 3D analysis was statistically significant for the several tested machine learning classifiers (all P> 0.05).ConclusionsRadiomic features from segmented tumor region in breast MRI were associated with ALN status. The separate radiomic analysis on 3D tumor volume showed a similar effect to the 2D analysis on the single representative slice in the tested machine learning classifiers.
| S-EPMC8581816 | biostudies-literature