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1.
Cancers (Basel) ; 16(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38730592

RESUMO

Invasive lobular carcinoma of the breast has different mammographic appearances, including spiculated or lobulated masses, architectural distortion, increased breast density, and the possibility of also being occult. Histologically, the morphology is also variable, as several patterns have been described beside the classical one, including the solid, the alveolar, the trabecular, the one with tubular elements, and others. Of 146 ILC cases, 141 were reviewed for mammographic appearance and 136 for histological patterns by two radiologist and two pathologists, respectively; 132 common cases were analyzed for possible associations between mammographic presentation and the histological patterns. Interobserver agreement on the presence or absence of a given mammographic morphology ranged from 45% (increased density) to 95% (occult lesion); the most common radiomorphology was that of a spiculated mass. Interobserver agreement on the presence or absence of a given histological pattern ranged between 79% (solid) and 99% (classical) but was worse when semi-quantification was also included. The mammography-pathology correlation was less than optimal. Multifocality was more commonly detected by histology. The identification of a mammographic mass lesion often coincided with a mass-like lesion on the histological slides and vice versa, but nearly half of the mammographically occult lesions were felt to have masses on histological slides assessed grossly. Histological patterns showed no obvious associations with one or the other mammographic appearance.

2.
J Pathol Clin Res ; 10(2): e12361, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618992

RESUMO

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Lobular/genética , Neoplasias da Mama/genética , Caderinas/genética , Biópsia , Colo , Microambiente Tumoral
3.
Pathol Res Pract ; 257: 155280, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608372

RESUMO

In breast conservative surgery, it is sometimes difficult to decide whether the cauterised tissue at the inked margin represents normal / hyperplastic or neoplastic tissue. We retrospectively assessed the value of ER, PR, CK5 and CK14 IHC in clarifying the nature of cauterised tissues at the margins concerning 34 lesions of 23 patients. 27 cases belonged to lesions that could not be adequately classified on the basis of the HE stains. Two thirds of them could be classified as non-neoplastic or neoplastic and two thirds of the remaining could be favourised as neoplastic or non-neoplastic, with 3/27 cases remaining uncertain. All 4 IHC reactions were helpful in classifying the lesions in almost half of the cases. However, 3 or 4 immunostains were supportive of the classification in 19/27. The most useful stains were the keratins, generally demonstrating a matching pattern of cell labelling with CK5 and CK14. ER and PR were somewhat less useful in classifying uncertain lesions. Considering all the 27 questionable lesions, IHC with ER, PR, CK5 and CK14 clarified the lesions at the cauterised margins in 23 cases. Taken all these considerations into account, CK5, CK14, PR and ER IHC may help in distinguishing between cautery damaged neoplastic and non-neoplastic tissues. All four IHC may yield the best support for decision making, but CK5 and/or CK14 may be sufficient in their own. The essential approach is that the results must be interpreted with caution, in the context of the given patient's disease, to avoid misinterpretations.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Imuno-Histoquímica , Queratina-14 , Queratina-5 , Margens de Excisão , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/metabolismo , Receptores de Progesterona/metabolismo , Queratina-5/metabolismo , Queratina-5/análise , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Pessoa de Meia-Idade , Queratina-14/metabolismo , Queratina-14/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Mastectomia Segmentar , Idoso , Adulto , Proliferação de Células
4.
Pathologica ; 116(1): 22-31, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38482672

RESUMO

Objective: To compare histological grade (G) of breast cancer and its components (scores for tubule formation - T, nuclear pleomorphism - P and mitotic counts - M) in core needle biopsies (CNBs) and surgical excision specimens (EXC) in patients treated with primary surgery (CHIR) or primary chemotherapy (PST). Methods: Grade of matched pairs of carcinomas in CNB and EXC was assessed according to the Nottingham grading system. Results: PST cases tended to have higher pretreatment G. Concordance rates in the CHIR (n = 760) and PST (n = 148) groups for T, P, M and G were 79%, 70%, 75%, 71% and 77%, 70%, 50%, 62%, respectively; differences in concordance rates were significant in M (p < 0.0001) and G (p = 0.024). For discordant cases in the CHIR group, CNBs tended to overestimate T and underestimate P, M and G, whereas in the PST group, the same trends were identified for T and P, but there was a significant tendency for M and G to be lower in EXC specimens. Conclusions: The reversal of M and G underestimation in CNB to "overestimation" in the PST group can only be explained with the effect of mitosis reduction following chemotherapy. Whether the posttreatment decrease in G reflects any prognostic value remains to be elucidated.


Assuntos
Neoplasias da Mama , Carcinoma , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Biópsia , Biópsia com Agulha de Grande Calibre , Prognóstico
5.
Geroscience ; 46(2): 2463-2488, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37987885

RESUMO

The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300-350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction's echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13's influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.


Assuntos
Cardiomiopatias , Hipertensão , Insuficiência Renal Crônica , Humanos , Ratos , Animais , Masculino , Idoso , Kisspeptinas , Receptores de Kisspeptina-1 , Ratos Wistar , Insuficiência Renal Crônica/complicações , Cardiomiopatias/complicações , Hipertensão/complicações , Fibrose
6.
Histopathology ; 83(5): 810-821, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37609779

RESUMO

AIMS: Invasive lobular carcinoma (ILC) has distinct morphology and association with loss of E-cadherin function. It has special clinical and imaging features, and its proper recognition is important. Following a recent proposal, we tested the value of the routine use of E-cadherin immunohistochemistry (IHC) in recognizing ILC. METHODS AND RESULTS: Five pathologists with experience in breast pathology from four Hungarian institutions histotyped 1001 breast cancers from diagnostic core biopsies or excision specimens randomly assigned to haematoxylin and eosin (HE) diagnosis first, followed by E-cadherin IHC; or to immediate HE and E-cadherin-based diagnosis. Of 524 cases with HE diagnosis, 73(14%) were deemed uncertain. E-cadherin made the initial histological type change in 14/524 cases (2.7%), including three with confident HE-based type allocation. Use of E-cadherin immunostaining was considered useful in 88/477 cases (18%) with immediate dual assessment, and typing uncertainty went down to 5% (25/477 cases), but was not zero. Collective assessment of 171 uncertain, difficult, nonclassical cases resulted in consensus diagnosis in most cases, but 15 cases were still doubtful as concerns their proper histological type. CDH1 gene sequencing was attempted and successful in 13; pathogenic genetic alterations were identified in seven cases. CONCLUSIONS: The routine use of E-cadherin IHC decreases the uncertainty in typing and improves the typing accuracy at the cost of potentially redundant additional immunostains. Furthermore, this procedure does not exclude uncertainty due to E-cadherin-positive ILCs, which are occasionally difficult to confidently label as ILC, especially when the growth pattern is not classic.

7.
Virchows Arch ; 483(3): 393-404, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37555982

RESUMO

The prognostic markers of lung squamous cell carcinoma (LSCC) are less investigated. The aim of our study was to evaluate tumour budding (TB), minimal cell nest size, nuclear diameter (ND), and spread through air spaces (STAS) among patients with resected LSCC, semi-quantitatively. Furthermore, we aimed to identify a grading system for the best prognostic stratification of LSCC. Patients who underwent surgical resection at the Department of Surgery, University of Szeged between 2010 and 2016 were included. Follow-up data were collected from medical charts. Morphological characteristics were recorded from histologic revision of slides. Kaplan-Meier analysis, log rank test and Cox proportional-hazards model, ROC curve analysis, and intraclass correlation were utilised. Altogether 220 patients were included. In univariate analysis, higher degree of TB, infiltrative tumour border, larger ND, the presence of single cell invasion (SCI) and STAS were associated with adverse prognosis. Based on our results, we proposed an easily applicable grading scheme focusing on TB, ND, and SCI. In multivariate analysis, the proposed grading system (pOS < 0.001, pRFS < 0.001) and STAS (pOS = 0.008, pRFS < 0.001) were independent prognosticators. Compared to the previously introduced grading systems, ROC curve analysis revealed that the proposed grade had the highest AUC values (AUCOS: 0.83, AUCRFS: 0.78). Each category of the proposed grading system has good (ICC: 0.79-0.88) reproducibility. We validated the prognostic impact of TB, SCI, ND, and STAS in LSCC. We recommend a reproducible grading system combining TB, SCI, and ND for proper prognostic stratification of LSCC patients. Further research is required for validation of this grading scheme.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Prognóstico , Reprodutibilidade dos Testes , Gradação de Tumores , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Pulmão/patologia , Estudos Retrospectivos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias
8.
Sci Rep ; 13(1): 14046, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37640761

RESUMO

Uremic cardiomyopathy is characterized by diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Dysregulation of the kisspeptin receptor (KISS1R)-mediated pathways are associated with the development of fibrosis in cancerous diseases. Here, we investigated the effects of the KISS1R antagonist peptide-234 (P234) on the development of uremic cardiomyopathy. Male Wistar rats (300-350 g) were randomized into four groups: (i) Sham, (ii) chronic kidney disease (CKD) induced by 5/6 nephrectomy, (iii) CKD treated with a lower dose of P234 (ip. 13 µg/day), (iv) CKD treated with a higher dose of P234 (ip. 26 µg/day). Treatments were administered daily from week 3 for 10 days. At week 13, the P234 administration did not influence the creatinine clearance and urinary protein excretion. However, the higher dose of P234 led to reduced anterior and posterior wall thicknesses, more severe interstitial fibrosis, and overexpression of genes associated with left ventricular remodeling (Ctgf, Tgfb, Col3a1, Mmp9), stretch (Nppa), and apoptosis (Bax, Bcl2, Casp7) compared to the CKD group. In contrast, no significant differences were found in the expressions of apoptosis-associated proteins between the groups. Our results suggest that the higher dose of P234 hastens the development and pathophysiology of uremic cardiomyopathy by activating the fibrotic TGF-ß-mediated pathways.


Assuntos
Cardiomiopatias , Peptídeos , Masculino , Ratos , Animais , Receptores de Kisspeptina-1 , Ratos Wistar , Apoptose , Cardiomiopatias/etiologia
9.
Cancers (Basel) ; 15(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37296968

RESUMO

(1) Background: The prognostic factors of microinvasive (≤1 mm) breast carcinoma are not completely clear. The aim of this study was to perform a systematic review and meta-analysis to clarify these factors. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Two databases were interrogated, PubMed and Embase, and papers in English were included to address this question. The selected studies were those that reported on female patients affected by microinvasive carcinoma, and on prognostic factors with a hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS). (3) Results: In total, 618 records were identified. After removing duplicates (166), identification, and screening (336 by title and abstract alone, 116 by full text and eventual supplementary material), 5 papers were selected. Seven different meta-analyses were conducted in this study, all referring to DFS, analyzing the following prognostic factors: estrogen receptor, progesterone receptor, HER2 status, multifocality and grade of microinvasion, patient's age, and lymph node status. Only lymph node status was associated with prognosis and DFS (total number of cases: 1528; Z = 1.94; p = 0.05). The other factors examined did not significantly affect prognosis (p > 0.05). (4) Conclusions: Positive lymph node status significantly worsens prognosis in patients with microinvasive breast carcinoma.

10.
Int J Mol Sci ; 24(10)2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37239898

RESUMO

A limited number of studies have focused on the mutational landscape of breast cancer in different ethnic populations within Europe and compared the data with other ethnic groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian breast cancer patients. We validated a subset of the identified variants at the DNA level using the Illumina TruSight Oncology (TSO) 500 assay. Canonical breast-cancer-associated genes with pathogenic germline mutations were CHEK2 and ATM. Nearly all the observed germline mutations were as frequent in the Hungarian breast cancer cohort as in independent European populations. The majority of the detected somatic short variants were single-nucleotide polymorphisms (SNPs), and only 8% and 6% of them were deletions or insertions, respectively. The genes most frequently affected by somatic mutations were KMT2C (31%), MUC4 (34%), PIK3CA (18%), and TP53 (34%). Copy number alterations were most common in the NBN, RAD51C, BRIP1, and CDH1 genes. For many samples, the somatic mutational landscape was dominated by mutational processes associated with homologous recombination deficiency (HRD). Our study, as the first breast tumor/normal sequencing study in Hungary, revealed several aspects of the significantly mutated genes and mutational signatures, and some of the copy number variations and somatic fusion events. Multiple signs of HRD were detected, highlighting the value of the comprehensive genomic characterization of breast cancer patient populations.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Hungria , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Mutação , Mutação em Linhagem Germinativa , Genômica
11.
Virchows Arch ; 482(5): 861-868, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37012444

RESUMO

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Queratina-5/metabolismo , Reprodutibilidade dos Testes , Mamoglobina A/metabolismo , Proteínas de Transporte , Fator de Transcrição GATA3/metabolismo , Proteínas Repressoras/metabolismo
12.
Cancers (Basel) ; 15(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36831541

RESUMO

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2-11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.

13.
Histopathology ; 82(1): 53-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36482278

RESUMO

Myoepithelial cells (MECs) constitute a continuous layer of cells surrounding the breast glands, localised between the epithelial cells (ECs) and the basal membrane. MECs play important roles in normal mammary gland as they produce basal membrane and stimulate secretion. During neoplastic transformation, MECs act as a barrier preventing stromal invasion. MECs themselves can undergo a great variety of changes, ranging from hyperplastic to metaplastic, to neoplastic, and giving rise to a wide spectrum of morphological pictures sometimes difficult to interpret on routine diagnoses. Several benign and malignant breast tumours can present features of MECs differentiation. As these latter tumours are quite infrequent, the purpose of the present study is to offer a review of the morphological spectrum of MECs lesions, with correlations to prognosis.

14.
Pathobiology ; 90(2): 104-113, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35947971

RESUMO

INTRODUCTION: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment. METHODS: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded. RESULTS: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63-21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60-34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92-0.94). DISCUSSION: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Reprodutibilidade dos Testes , Invasividade Neoplásica , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos
15.
Pathol Oncol Res ; 29: 1611365, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38188613

RESUMO

Among the many consecutive theories of cancer, the stem cell theory is currently the most accepted one. Cancer stem cells are located in small niches with specific environment, renew themselves and are believed to be responsible for many recurrences. They can be highlighted with stem cell markers, but often these markers also label tumor cells, and this may represent a phenotypical change associated with prognosis. In this study, we attempted to match tumor outcomes with the expression of the following stem cell markers: ALDH1, AnnexinA1, CD44, CD117, CD166, Nanog and oct-4. Tissue microarray blocks from triple-negative breast cancers were immunostained for the listed markers, and their expression by the majority of tumor cells (diffuse positivity) was correlated with prognosis. Of the 106 tumors investigated, diffuse positivity was seen in 7 (ALDH1), 33 (AnnexinA1), 53 (CD44), 44 (CD117 membranous only), 49 (CD117), 72 (CD166), 19 (Nanog), and 11 (oct-4) cases. With a median follow-up of 83 months, ALDH1 and CD117 expression was associated with DFS, whereas CD44, CD117 and CD166 were associated with OS estimates, based on Kaplan-Meier analyses. In the multivariate Cox proportional hazard models (including the examined markers and clinicopathological data which had a statistical impact in the univariate analysis), the pN category and the lack of ALDH1 expression were independent prognosticators for DFS, and the pN category and diffuse CD44 staining were independent prognosticators for OS. In the multivariate analysis including all of the examined clinicopathological data and markers, only CD117 showed a statistical impact on OS. We failed to demonstrate a prognostic impact for most stem cell markers tested in triple-negative breast cancer, but lack of ALDH1 staining and CD44 expression appears as of prognostic value, requiring further examination in independent studies.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Prognóstico , Estimativa de Kaplan-Meier , Análise Multivariada , Células-Tronco Neoplásicas
16.
Arch Pathol Lab Med ; 146(11): 1308-1318, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270029

RESUMO

CONTEXT.­: The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. OBJECTIVE.­: To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. DATA SOURCES.­: Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. CONCLUSIONS.­: The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.


Assuntos
Neoplasias da Mama , Patologia Clínica , Humanos , Feminino , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/cirurgia , Metástase Linfática , Linfonodos/cirurgia
18.
Mod Pathol ; 35(12): 1812-1820, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35922548

RESUMO

Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC). Recent results of central pathology review of two large randomized clinical trials have demonstrated relative overdiagnosis of ILC, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons of this discrepancy, we undertook a worldwide survey on the current practice of diagnosing BC as ILC. A survey was drafted by a panel of pathologists and researchers from the European lobular breast cancer consortium (ELBCC) using the online tool SurveyMonkey®. Various parameters such as indications for IHC staining, IHC clones, and IHC staining procedures were questioned. Finally, systematic reporting of non-classical ILC variants were also interrogated. This survey was sent out to pathologists worldwide and circulated from December 14, 2020 until July, 1 2021. The results demonstrate that approximately half of the institutions use E-cadherin expression loss by IHC as an ancillary test to diagnose ILC and that there is a great variability in immunostaining protocols. This might cause different staining results and discordant interpretations. As ILC-specific therapeutic and diagnostic avenues are currently explored in the context of clinical trials, it is of importance to improve standardization of histopathologic diagnosis of ILC diagnosis.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Carcinoma Ductal de Mama , Carcinoma Lobular , Feminino , Humanos , Neoplasias da Mama/patologia , Caderinas/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Imuno-Histoquímica , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Pathol Oncol Res ; 28: 1610373, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845921

RESUMO

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/patologia , Consenso , Feminino , Humanos , Hungria , Oncologia , Prognóstico
20.
Orv Hetil ; 163(4): 157-160, 2022 01 23.
Artigo em Húngaro | MEDLINE | ID: mdl-35066489

RESUMO

Összefoglaló. Az urachus tumorai és egyéb betegségei ritkák. A 67 éves férfi anamnézisében ismétlodo húgyúti fertozés szerepelt ciprofloxacinterápiával. Cisztoszkópia során a húgyhólyag felso részének másodlagos érintettségére utaló bullosus nyálkahártya képe mutatkozott. Az ezt követo CT-felvételek alapján az alsó medián hasfallal, húgyhólyaggal, belekkel összefüggo tumor iránydiagnózisát állították fel. A kivizsgálás során kialakuló ileus miatt Hartmann-mutétet végeztek, a tumoros jellegu elváltozás teljes és az érintett szervek részleges eltávolításával. A kórszövettani vizsgálat daganatos elváltozást nem talált, hasi, vélhetoen urachuseredetu actinomycosist igazolt: erre az eredetre a lokalizáció és a tünetek közt szereplo köldökváladékozás alapján lehetett gondolni, annak ellenére, hogy urachusmaradványt szövettanilag nem sikerült igazolni a mikroabszcedáló gyulladás által érintett szövetekben. A betegnél amoxicillinterápia indult. Átmeneti, hólyag melletti vizeletcsorgást követoen a beteg tünet- és panaszmentesen távozott a kórházból, de 13 nappal késobb a hasfali seb sterilnek véleményezett szétválása miatt ismét hospitalizálni kellett. Negatív nyomású sebkezelést követoen sikerült a hasat ismét zárni. A beteg ismét tünetmentessé vált, és fenntartott antibiotikumkezelés mellett hagyta el a kórházat. Az urachuskörnyéki tumorszeru elváltozások között az actinomycosis lehetoségét is szem elott kell tartani a differenciáldiagnosztikában. Orv Hetil. 2022; 163(4): 157-160. Summary. Tumours and other diseases of the urachus are rare. A 67-year-old male presented with a history of recurrent urinary tract infection and ciprofloxacin therapy. Cystoscopy suggested secondary involvement of the bullous upper bladder wall. The subsequent CT-based diagnosis was of a tumour infiltrating the lower median abdominal wall, the urinary bladder and bowels. Bowel obstruction developed and this led to partial resection of the involved organs along with a Hartmann's procedure. Histology revealed no neoplastic conditions, but proved abdominal actinomycosis of probable urachal origin based on the location of the tumour-like lesion and umbilical discharge among the symptoms. Urachal remnants were not identified in the perivesical tissues involved by the microabscess forming inflammation. Amoxicillin therapy was initiated. After a temporary urine leakage from the bladder, the patient became symptomless and was emitted from hospital. After 13 days, he was readmitted because of abdominal wound disruption, which was treated with negative-pressure wound therapy before the abdomen could be closed. At the time of reporting, he is still on amoxicillin, and has become symptomless again. Actinomycosis should be considered in the differential diagnosis of mass lesions of the urachal region. Orv Hetil. 2022; 163(4): 157-160.


Assuntos
Actinomicose , Neoplasias da Bexiga Urinária , Actinomicose/diagnóstico , Idoso , Hospitais , Humanos , Masculino , Bexiga Urinária , Neoplasias da Bexiga Urinária/diagnóstico por imagem
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