Clinical-pathological Characterization Research Articles

Clinical-pathological characterization of patients with HER2 negative breast cancer submitted to adjuvant docetaxel/cyclophosphamide (TC), TC4 versus TC6.

e12530 Background: The optimal number of cycles of adjuvant docetaxel and cyclophosphamide (TC) in patients with HER2 negative breast cancer is unknown. The serious long-term adverse events associated with anthracyclines led researchers to question the risk-benefit ratio of anthracycline-based regimens, especially in those without axillary lymph node involvement, leading to an increasing trend to omit anthracyclines in adjuvant treatment. Therefore, we do not know for sure which clinical-pathological characteristics would favor the use of TC4 versus TC6. Objective: To evaluate the clinical-pathological characteristics of patients who received adjuvant treatment for invasive breast cancer, her2 negative, stage I-III with TC4 or TC6 in a Brazilian service. Methods: This is a retrospective observational cohort study of patients diagnosed with invasive breast cancer, her2 negative, stage I-III, who received adjuvant treatment with TC4 or TC6, between January 2010 and December 2022 at AC Camargo Cancer Center, São Paulo, Brazil. Results: We analyzed 186 patients, 98% female, 52.3% pre-menopausal, 68.7% had at least one comorbidity, 10% mutation in the BRCA1/2 gene, 5% had a previous history of DCis or IDC. 62.2% underwent breast-conserving surgery and 80% underwent sentinel lymph node (SL). Regarding the pathological characteristics of the tumor 82.9% invasive ductal carcinoma (IDC), 42.7% histological grade (HG) III, 90% were hormone receptor positive (HR+) and only 10% triple negative (TN), staging 66% pT1, 71% pN0, being grouped into 63.7% stage I, 34.6% stage II; 1.7% stage III. Only 9% underwent oncotype, 5% of them had some contraindication to anthracycline. Regarding treatment groups 72.4% received TC4 versus 27.6% TC6. There were no treatment-related deaths. Regarding the TC4 / TC6 groups (%) and clinical-pathological characteristics: pre-menopausal 60.5 / 49% ( p= 0.225), comorbidity 3 / 6% ( p= 0.400), contraindication to anthracycline 4.7 / 6% ( p= 0.714). Conservative surgery 61.5 / 64% ( p= 0.894), SL 81 / 78% ( p= 0.504), GH III 39.8 / 50% (p = 0.334), pT2 staging 26.4 / 40 % (p = 0.087), pN1 11.7/ 22% (p = 0.050), stage I 65.9/58%, II 33.3 / 38%, III 0.8 /4 % (p = 0.212). RH- 8.7 / 14% (p = 0.444). Did not complete treatment 3.2 / 12% (p = 0.033), toxicities G3/4 9.7 / 12.5% (p = 0.791), FN G3/4 3.8 / 4% (p = 1.00) and neuropathies 8.9 / 28.6% (p = 0.002). Late toxicities 5.7 / 18.4% (p = 0.018). Extended hormone therapy 35/ 50% (p = 0.142). Systemic recurrences 12.5% / 2% (p = 0.566). Conclusions: TC6 was more indicated in patients with GH III, pT2 and/or pN1, stage II and III, RH-, therefore patients who received TC6 had a lower chance of completing the treatment, as well as greater toxicities, mainly late peripheral neuropathy, and more indications of extended hormone therapy, however those who performed the TC6 had less chance of systemic recurrences.

Findings suggestive of coronary microvascular dysfunction in cats with myocardial ischemia.

Background:Myocardial infarction (MI) is an important cause of death and disability among humans worldwide. Few studies have reported the occurrence of MI in small animals as well. Reports in human medicine indicate that up to 30% of patients with clinical signs compatible with myocardial ischemia suggestive of coronary disease exhibit normal epicardial arteries at angiography. These symptoms have been associated with a syndrome characterized by alterations in cardiac microvasculature, known as coronary microvascular dysfunction (CMD). Aim:This study aimed to describe the necropsy findings and clinical-pathological characterization (when available) of cats with histopathological findings suggesting CMD. Methods:Necropsy records of cats presenting histopathological diagnosis compatible with acute and/or chronic MI, with normal epicardial arteries and microvascular disorders were evaluated.Results:Twenty animals met the inclusion criteria. Eight cats (40%) exhibited findings compatible with mild hypertrophic cardiomyopathy (HCM) without left atrial enlargement, one (5%) presented restrictive cardiomyopathy, and another one (5%) had lesions consistent with histiocytoid cardiomyopathy. The remaining cats (50%) showed alterations compatible with severe HCM with left atrial enlargement. In all cases, epicardial arteries were normal (without obstruction). All the evaluated hearts exhibited myocardial multifocal fibrosis along with replacement of cardiomyocytes by adipose tissue and blood vessels with hyperplasia and hypertrophy of the muscular layer with protrusion of the nuclei of the endothelial cells.Conclusion:These findings suggest the presence of microvascular dysplasia of the coronary arteries. Further studies are necessary to confirm and clinically characterize these results.

Development and Validation of the Trans-Omics Model for Pancreatic Adenocarcinoma

Aim: To develop a trans-omics-based molecular clinicopathological algorithm for predicting pancreatic adenocarcinoma prognosis, we performed a comprehensive analysis of the expression levels of mRNA, DNA methylation and DNA copy number in The Cancer Genome Atlas dataset. Materials & methods: Based on the least absolute shrinkage and selection operator method - COX regression analysis, a trans-omics-based classifier was established to predict overall survival. Nomogram was constructed by combining the classifier band clinical pathological characterization. Results: Based on trans-omics, we developed a 10-gene-based classifier and a molecular-clinicopathologic nomogram for predicting overall survival with satisfactory accuracy. Conclusion: Trans-omics-based classifier and molecule-clinicopathological nomogram based on the classifier can accurately predict the prognosis of pancreatic adenocarcinoma patients.

Histology of the spleen in immune thrombocytopenia: clinical-pathological characterization and prognostic implications.

Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.

Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer.

Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization.Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples.Results: A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0–1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Toll-like receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: SFTPA1 (P = 0.023), SFTPA2 (P = 0.027), SFTPB (P = 0.02), and SFTPC (P = 0.047).Conclusions: We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

Abstract 2336: Clinical-pathological characterization of the immunomodulator subgroup of triple negative breast cancer as a promising step in the selection of patients in personalized immunotherapies

Abstract Introduction: Triple Negative Breast Cancer (CMTN) represents 23.1% of breast cancer cases in Mexico, is defined as a tumor that is absent of hormone receptors (estrogen and progesterone) and low HER2 overexpression and clinically is characterized by its agressive tumoral behavior. Lehmann et al. described an immunomodulatory (IM) group which is composed of genes for immune antigens and transduction pathways of immune signals and cytokines. Recent studies have shown that patients with the IM phenotype have a better prognosis. So it is important to continue with the description of this subgroup as the first step for personalized therapies in this heterogeneous tumor. Methodology: Retrospective clinical study, patients with diagnosis of CMTN, attended at the National Cancer Institute of Mexico (Total: 69 patients) were included. Following, the extraction of RNA from the primary tumor tissue of CMTN paraffin blocks was performed to subsequently generate labeled cDNA for hybridization in Affymetrix® Human Gene 2.0 microarrays, to later carry out the scanning and analysis of the data. For the analysis of microarrays we used the free software R and Bioconductor.65. And then the classification of patients using the platform "TNBCtype (http://cbc.mc.vanderbilt.edu/tnbc/)". And finally the analysis of survival, univariate and multivariate through SPSS. Results: We observed some clinical variables with statistical difference such as radiotherapy (p<0.001), metastasis to lung (p=0.009), liver (p=0.013), and central nervous system (p=0.0029), as well as the Lehmann classifier showed significant difference between patients classified as IM vs. No IM (p=0.04). Conclusions: the IM classifier could not only serve as an excellent prognostic classification in CMTN but as a predictor of immunological treatments. Citation Format: Ruben R. Bautista, Oscar Gerardo A. Rodríguez, Alfredo H. Miranda, Alejandro Z. Dehesa. Clinical-pathological characterization of the immunomodulator subgroup of triple negative breast cancer as a promising step in the selection of patients in personalized immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2336.

Clinical-pathological Characterization and Outcomes of Metastatic Urothelial Cancer in Latin America: Retrospective and Translational Multicenter Database

Clinical-pathological Characterization and Outcomes of Metastatic Urothelial Cancer in Latin America: Retrospective and Translational Multicenter Database

The expression of MMP-9 in breast carcinoma and its significance

Objective To explore the expression of matrix metalloproteinase-9 (MMP-9) in breast carcinoma and the relationship between the expression and clinical pathological characterization. Methods Specimens taken from 50 fresh resected breast carcinoma tissue and 16 normal breast tissue were selected. Tissue sections were stained by EnVision™ immunohistochemistry with MMP-9 as monoclonal antibody. The expression of MMP-9 in breast carcinoma and the relationship between the expression and clinical pathological characterization were studied. Results The positive rate of MMP-9 breast cancer carcinoma was 59.32%, which was significantly higher than that of normal breast tissue 9.62%, with statistical significance (P<0.01). The average rank and score of MMP-9 in the metastatic tissue of breast carcinoma were higher than that of no metastatic breast cancer tissue (P<0.01). Conclusions MMP-9 may be related to the destruction of extracellular matrix and basement membrane near the surface of breast cancer cells, thereby promoting the invasion and metastasis of breast cancer. Key words: Breast neoplasms/ME; Matrix metalloproteinase 9/ME

Clinical-pathological characterization and study of polymorphisms of T-helper-1 and 2 (Th1 / 2) responses in immune-mediated diseases with oral manifestations: oral lichen planus and amalgam-associate oral lichenoid reaction

Clinical-pathological characterization and study of polymorphisms of T-helper-1 and 2 (Th1 / 2) responses in immune-mediated diseases with oral manifestations: oral lichen planus and amalgam-associate oral lichenoid reaction

Clinical–Pathological Characterization of Diabetic Foot Infections

The present study has 3 aims: (a) to characterize the clinical and pathological features of diabetic foot infections, (b) to show the range of clinical presentations of moderate infections, and (c) to analyze the different behavior of diabetic foot osteomyelitis regarding to its clinical presentation. A definitive diagnosis of the type of infection was made based on intraoperative findings and histopathology. Diabetic foot infections were classified into 2 types: soft tissue and bone infections. Mild infections were always superficial. Severe infections included 75% of necrotizing soft tissue infections. Moderate infections showed ample range of clinical presentations. Eighty-one patients presented osteomyelitis. Osteomyelitis was further classified as follows: osteomyelitis without ischemia and without soft tissue involvement (class 1), osteomyelitis with ischemia without soft tissue involvement (class 2), osteomyelitis with soft tissue involvement (class 3), and osteomyelitis with ischemia and soft tissue involvement (class 4). Forty-eight patients (59.3%) with osteomyelitis underwent conservative surgery, 32 (39.5%) had minor amputations including 9 open transmetatarsal amputations, and there was 1 (1.2%) major amputation. The characterization of osteomyelitis into 4 classes showed a statistically significant trend toward increased severity and increased amputation rate and mortality. In conclusion, the clinical presentation of foot infections in diabetic patients is very heterogeneous and can be classified into soft tissue infections (cellulitis, superficial and deep abscesses, and necrotizing soft tissue infections) and osteomyelitis, which was the most frequent type of infection found in the author's series. Their division into 4 classes showed a statistically significant trend toward increased severity, amputation rate, and mortality. The diagnosis of deep soft tissue infections associated with osteomyelitis may be difficult to achieve before surgery.

Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

Skeletal muscle in patients with cancer undergoes many morphological changes due to immuno-inflammatory factors of tumor origin or treatment.T he latest event of these changes is cancer cachexia. Aim of the study is to identify myopathic features in skeletal muscle biopsies from weight stable patients with colorectal cancer and without cachexia or asthenia / weakness, that could possibly provide new diagnostic and prognostic cancer biomarkers. Morphometric analyses and immunohistochemical studies were performed on intraoperative muscle biopsies from patients with colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. A rectus abdominis biopsy was taken in all patients and controls.A correlation between histopathologic findings and clinical characteristics, circulating inflammatory biomarkers and markers of muscle necrosis,surgery data and cancer phenotype were investigated.. Forty four patients (21male/23 female) and 17 controls (6 male/11 female) (p=NS) were studied. In cancer patients&amp;rsquo;biopsies we observed asubclinical myopathy characterized by an abnormal distribution of myonuclei, which are localized inside the myofiber rather than at the periphery, and by the presence of regenerating muscle fibers. The percentage of myofibers with internalized nuclei is significantly higher in patients (median= 9%, IQR= 3.7-18.8) than in controls (median= 2.7%, IQR= 1.7-3.2) ( p=0.0002). In patients we observed an inverse correlation between the number of centronucleated fibers and the presence of node metastasis (N+)(&amp;rho;)=-0.64 (p=0.002). Patients affected with colorectal cancer display early sign of a myopathy, characterized by centronucleated and regenerating myofibers. This myopathy appears to be associated with an early stage of neoplasia and it could be an adaptive response of muscle to cancer. We hope a future application of these findings as a possible early diagnostic and prognostic biomarker of neoplasia.