Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues.

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.

Galanin Receptors (GalR1, GalR2, and GalR3) Expression in Colorectal Cancer Tissue and Correlations to the Overall Survival and Poor Prognosis of CRC Patients.

Colorectal cancer (CRC) is the second most common cause of cancer in women and the third in men. The postoperative pathomorphological evaluation of patients with CRC is extremely important for future therapeutic decisions. Although our previous studies demonstrated high galanin (GAL) presence within tumor tissue and an elevated concentration of GAL in the serum of CRC patients, to date, there is a lack of data regarding GAL receptor (GalR) protein expression in CRC cells. Therefore, the aim of this study was to evaluate the presence of all three types of GalRs (GalR1, GalR2 and GalR3) within epithelial cells of the human colon and CRC tissue with the use of the immunohistochemical method and to correlate the results with the clinical-pathological data. We found stronger immunoreactivity of GalR1 and GalR3 in CRC cells compared to epithelial cells of the unchanged mucosa of the large intestine. No differences in the GalR2 protein immunoreactivity between the studied tissues were noted. We also found that the increased immunoexpression of the GalR3 in CRC tissue correlated with the better prognosis and longer survival (p < 0.0079) of CRC patients (n = 55). The obtained results suggest that GalR3 may play the role of a prognostic factor for CRC patients. Based on data from the TCGA-COAD project deposited in the GDC Data Portal, we also found that GalR mRNA in cancer samples and the adjacent normal tissue did not correlate with immunoexpression of the GalR proteins in CRC cells and epithelial cells of the unchanged mucosa.

Clinicopathologic retrospective analysis of blastic plasmacytoid dendritic cell neoplasms.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one of the aggressive rare hematopoietic malignancies with predilection to the skin, primarily found in adults. The precise incidence of BPDCN is difficult to estimate due to constantly changing nomenclature and lack of precise defining criteria prior to the 2008 WHO classification system. There are not many cases described in the literature, what makes the diagnostic process challenging. Skin lesions such as erythematous infiltrates and nodules are usually the first manifestation of the disease. Therefore, in doubtful diagnostic cases, dermatologists should perform histopathological and immunohistochemistry examinations along with hematological and oncological cooperation, as early diagnosis and appropriate treatment is essential for improvement of the disease course. This analysis, despite the small number of patients may provide useful information on the clinical and histopathological features of this rare malignancy.

Recanalization and remodeling of the great saphenous vein caused by the large melanoma's cutaneous metastasis.

AIM OF THE STUDY: Large melanoma tumour caused arterial remodelling of the distal part of the great saphenous vein. The metastasis occurred at the site where inguinal lymphadenectomy was previously performed and the proximal part of the great saphenous vein was resected.The aim of this study is the presentation of such a rare observation and literature overview concerning melanoma metastasis and possible stimuli causing remodelling of veins. MATERIAL AND METHODS: Macroscopic and microscopic analyses of the large blood vessel that supplies melanoma were made. The size and structure of the blood vessel was compared with the regular great saphenous vein. RESULTS: The macroscopic examinations allowed us to ascertain that the blood vessel that was identified intraoperatively as the great saphenous vein, has a thick, stiff wall. The microscopic analysis allowed demonstrated that the tunica media was typical for a muscular artery morphology. The morphometric analysis revealed that the blood vessel wall in the area of metastatic tumour was much thicker than the wall of a regular great saphenous vein. CONCLUSIONS: This malignant melanoma skin metastases caused the recanalisation of the great saphenous vein the lumen of which was obliterated during the initial surgical treatment. The metastatic tumour supplied by large blood vessels grew extensively and caused arterial remodelling of the venous wall.

Plasticity of neuropeptidergic neoplasm cells in the primary and metastatic Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous carcinoma with characteristics of neuroendocrine tumor. We performed immunohistochemical analysis to demonstrate the presence of various neuropeptides within cells of MCC resected from a 75-year old woman. The cells of primary tumor of cheek were compared with the cells of regional right submandibular metastatic tumor which was found eight months later. A double- staining IHC for the pan-neuronal marker, PGP 9.5, and selected neuropeptides in the tissue material obtained from both locations was performed. Single multipolar cells in the main mass of primary tumor stained positively for PGP 9.5 and such neuropeptides as GAL, VIP, PACAP, NPY and CGRP. Moreover, we demonstrated for the first time the presence of neuropeptides in metastatic MCC cells. In the metastatic tumor, cells showing the co-localization of PGP-9.5 and neuropeptides were more numerous, mostly of oval shape, and significantly smaller than in the primary tumor. Thus, the progression of MCC may be associated with the acquisition by its cells of new morphological and biological features.

Advanced abdominal arterial calcification sparing kidney allograft--case report.

Excess and progressing arterial calcification is a frequent finding in patients with chronic kidney disease and in diabetics. Vascular calcification present in patients on dialysis, usually continues to progress (although possibly with slower rate) in patients after kidney transplantation. These observations are limited mostly to aorta and coronary arteries; virtually no data exist on progression in vascular calcification within the vasculature of transplanted kidney. The case report presents the patient with diabetes and non-functioning renal transplant back on dialysis with extremely severe intra-abdominal artery calcification, sparing renal artery of transplanted kidney. Calcification did not develop within transplanted kidney despite 10 years of exposition to diabetic environment and a few years of chronic kidney disease after transplantation, including CKD-T stage 5 for at least one year after re-starting of dialysis. To the best of our knowledge, this is the second report ever describing sparing of kidney graft from calcification despite disseminated calcification in other vascular beds. It is tempting to speculate that some "intrinsic" factors exist within the transplanted kidney that protects it from calcification despite exposure to procalcifying milieu of diabetes and uremia.