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1.
Am J Gastroenterol ; 116(9): 1859-1867, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34313623

RESUMO

INTRODUCTION: Corpus atrophic gastritis (CAG) is associated with intestinal metaplasia (IM) and pseudopyloric metaplasia (PPM). Prospective data on corpus mucosa PPM and its link to the development of gastric cancer (GC) are lacking. This study aimed to investigate the relationship between the presence of corpus mucosa PPM at baseline and the development of GC at follow-up in patients with CAG. METHODS: A longitudinal cohort study was conducted on patients with consecutive CAG adhering to endoscopic-histological surveillance. Patients were stratified for the presence/absence of corpus PPM without concomitant corpus IM at baseline, and the occurrence of gastric neoplastic lesions at the longest available follow-up was assessed. RESULTS: A total of 292 patients with CAG with a follow-up of 4.2 (3-17) years were included. At baseline, corpus PPM without corpus IM was diagnosed in 62 patients (21.2%). At the follow-up, GC was detected in 5 patients (1.7%) and gastric dysplasia (GD) in 4 patients (1.4%). In all these 9 patients with GC/GD at the follow-up, corpus IM was present at baseline and follow-up. Age <50 years (odds ratio [OR] 2.5), absence of pernicious anemia (OR 4.3), and absence of severe corpus atrophy (OR 2.3) were associated with corpus PPM without corpus IM. DISCUSSION: At the 4.2-year follow-up, in patients with CAG characterized at baseline with corpus PPM without corpus IM, GC or GD was not observed because these lesions were consistently associated with corpus IM. Corpus PPM without corpus IM was associated with younger age, absence of pernicious anemia, and severe corpus atrophy, suggesting a lower stage of disease progression. Corpus PPM alone seems not to be associated with GC, whose development seems to require the presence of corpus IM as a necessary step.


Assuntos
Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Metaplasia/complicações , Neoplasias Gástricas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Gastrite Atrófica/patologia , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Adulto Jovem
2.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069715

RESUMO

Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing (POPDC) gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell-cell interaction, and cell migration. POPDC1 and POPDC3 downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves POPDC gene dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for expression levels of POPDC1-3 and several suggested IM biomarkers, using immunohistochemistry and qPCR. Immunostaining indicated lower POPDC1 and POPDC3 labeling in IM compared with normal tissues. Significantly lower POPDC1 and POPDC3 mRNA levels were measured in IM and GC biopsies and in GC-derived cell lines. The reduction in focal IM was smaller than in extensive IM that resembled GC tissues. POPDC1 and POPDC3 transcript levels were highly correlated with each other and inversely correlated with LGR5, OLFM4, CDX2, and several mucin transcripts. The association of POPDC1 and POPDC3 downregulation with IM-to-GC transition implicates a role in tumor suppression and highlights them as potential biomarkers for GC progression and prospective treatment targets.


Assuntos
Moléculas de Adesão Celular/metabolismo , Proteínas Musculares/metabolismo , Lesões Pré-Cancerosas/patologia , Idoso , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Feminino , Mucosa Gástrica/patologia , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/metabolismo , Metaplasia/patologia , Pessoa de Meia-Idade , Proteínas Musculares/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Estudos Prospectivos , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
3.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071181

RESUMO

Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.


Assuntos
Metaplasia/metabolismo , Lesões Pré-Cancerosas/metabolismo , Neoplasias Gástricas/metabolismo , Progressão da Doença , Variação Genética , Metaplasia/genética , MicroRNAs , Microbiota , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
4.
Am J Gastroenterol ; 116(6): 1230-1237, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074827

RESUMO

INTRODUCTION: The influence of sedation on the endoscopic detection rate of upper gastrointestinal (UGI) early cancer (EC) and precancerous lesions, including high-grade intraepithelial neoplasia (HGIN) and low-grade intraepithelial neoplasia, has not been assessed. The aim of this research is to assess whether the use of sedation can help improve the detection rate of UGI EC and precancerous lesions. The second objective is to evaluate its potential influencing factors. METHODS: The study includes 432,202 patients from a multicenter database from January 2012 to July 2019. Information on endoscopic findings and histology biopsies was obtained from endoscopy quality-control system. Associations of sedation with the detection rate of EC and precancerous lesions were assessed. RESULTS: The sedation group has a higher detection rate of UGI EC and HGIN compared with the no-sedation group, whereas the detection rate of low-grade intraepithelial neoplasia was similar between the 2 groups. There were more cases examined by using staining, image enhancement, or magnifying techniques in the sedation group (P < 0.001). And, the mean observation time was also longer in the sedation group (P < 0.001). The type 0-IIb esophageal HGIN and EC cases were significantly increased in the sedation group. No significant difference was detected on lesion subtypes for gastric HGIN and EC according to the Paris classification. More gastric HGIN and EC were detected at gastric body in the sedation group (P = 0.001). DISCUSSION: Sedation may improve the endoscopic detection rate of EC and HGIN in the UGI tract probably through enhancing the use of accessary endoscopic techniques, prolonging observation time, and taking more biopsies in different locations (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B926).


Assuntos
Sedação Consciente , Endoscopia Gastrointestinal , Neoplasias Esofágicas/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Biópsia , Detecção Precoce de Câncer , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Lesões Pré-Cancerosas/patologia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/patologia
5.
BMJ ; 373: n877, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947661

RESUMO

OBJECTIVE: To assess the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC. DESIGN: Case-control study. SETTING: Linkage to the multi-generation register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden. PARTICIPANTS: 68 060 patients with CRC and 333 753 matched controls. MAIN OUTCOME MEASURES: Multivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC. RESULTS: After adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, P<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, P<0.001 for trend). A particularly strong association was found for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P<0.001 for interaction). CONCLUSIONS: After adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.


Assuntos
Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Anamnese , Lesões Pré-Cancerosas/epidemiologia , Reto/patologia , Crianças Adultas/estatística & dados numéricos , Idade de Início , Idoso , Estudos de Casos e Controles , Colo/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Sistema de Registros/estatística & dados numéricos , Medição de Risco/estatística & dados numéricos , Fatores Sexuais , Irmãos , Suécia/epidemiologia
6.
Nat Commun ; 12(1): 2722, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976164

RESUMO

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.


Assuntos
Adenocarcinoma in Situ/genética , Adenocarcinoma de Pulmão/genética , Carcinogênese/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Lesões Pré-Cancerosas/genética , Transcriptoma , Adenocarcinoma in Situ/imunologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Carcinogênese/imunologia , Carcinogênese/patologia , Aberrações Cromossômicas , Células Clonais , Variações do Número de Cópias de DNA , Metilação de DNA , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade Inata , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/imunologia , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Transdução de Sinais , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
7.
Surg Clin North Am ; 101(3): 381-389, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34048759

RESUMO

To care and treat patients with esophageal cancer, one must first understand the epidemiology of Barrett's esophagus (BE). BE is defined as the intestinal metaplasia occurring within the esophagus from normal squamous epithelium to abnormal specialized columnar epithelium. BE, while first described by Allison in 1948, was attributed to Norman Barrett in 1950, who reported a case of chronic peptic ulcer in the lower esophagus that was covered by columnar epithelium.


Assuntos
Adenocarcinoma/epidemiologia , Esôfago de Barrett/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Esôfago/patologia , Lesões Pré-Cancerosas/epidemiologia , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Humanos , Metaplasia , Lesões Pré-Cancerosas/patologia , Estados Unidos/epidemiologia
8.
Surg Clin North Am ; 101(3): 391-403, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34048760

RESUMO

Barrett esophagus (BE), defined as intestinal metaplasia of the distal esophageal mucosa, typically results from chronic gastroesophageal reflux disease and is the only known precursor of esophageal adenocarcinoma. The standard of care for the management of early esophageal neoplasia in the setting of BE has changed drastically over the past 15 years. Further investigation into diagnostic and therapeutic adjuncts will continue to improve our ability to control or cure BE before its advancement to a life-threatening malignancy.


Assuntos
Adenocarcinoma/prevenção & controle , Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/prevenção & controle , Esofagoscopia/métodos , Fundoplicatura , Refluxo Gastroesofágico/terapia , Lesões Pré-Cancerosas/cirurgia , Inibidores da Bomba de Prótons/uso terapêutico , Técnicas de Ablação , Adenocarcinoma/patologia , Esôfago de Barrett/etiologia , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Refluxo Gastroesofágico/complicações , Humanos , Lesões Pré-Cancerosas/patologia
9.
Wiad Lek ; 74(3 cz 1): 388-394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813438

RESUMO

OBJECTIVE: The aim: To conduct a morphological study of endometrial tissue to identify changes characteristic of viral lesions to develop improved antirelapse treatment of HPE in women of reproductive age. PATIENTS AND METHODS: Materials and methods: We surveyed 90 patients of the gynecological department who sought medical for hyperplastic processes of the endometrium in reproductive age. All women underwent hysteroscopy, the resulting material was subjected to morphological examination. RESULTS: Results: It became known that the virus is involved in the pathogenesis of endometrial hyperplasia. It is likely that it exists in epitheliocytes not only as a "passenger", but also as an etiological factor. It became known that it was in complex hyperplasia with atypia that the percentage reached the highest level, which is a precancerous condition. CONCLUSION: Conclusions: Typical morphological change of the endometrium - multinucleation, multinuclearity and koilocytotic atypia in women of childbearing age with HPE - was revealed. The presence of infectious pathogens in the endometrium of patients with HPE can be regarded as one of the possible triggers for the development of hyperplastic processes.


Assuntos
Hiperplasia Endometrial , Lesões Pré-Cancerosas , Hiperplasia Endometrial/patologia , Endométrio/patologia , Feminino , Humanos , Hiperplasia/patologia , Histeroscopia , Lesões Pré-Cancerosas/patologia , Gravidez
10.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810183

RESUMO

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.


Assuntos
Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etiologia , Integração Viral , Transformação Celular Viral , Biologia Computacional/métodos , Feminino , Genoma Viral , Genótipo , Humanos , México/epidemiologia , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Análise de Sequência de DNA , Displasia do Colo do Útero/patologia
11.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807389

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that play a pivotal role in many aspects of cell biology, including cancer development. Within esophageal cancer, miRNAs have been proved to be involved in all phases of carcinogenesis, from initiation to metastatic spread. Several miRNAs have been found to be dysregulated in esophageal premalignant lesions, namely Barrett's esophagus, Barrett's dysplasia, and squamous dysplasia. Furthermore, numerous studies have investigated the alteration in the expression levels of many oncomiRNAs and tumor suppressor miRNAs in esophageal squamous cell carcinoma and esophageal adenocarcinoma, thus proving how miRNAs are able modulate crucial regulatory pathways of cancer development. Considering these findings, miRNAs may have a role not only as a diagnostic and prognostic tool, but also as predictive biomarker of response to anti-cancer therapies and as potential therapeutic targets. This review aims to summarize several studies on the matter, focusing on the possible diagnostic-therapeutic implications.


Assuntos
Neoplasias Esofágicas/genética , MicroRNAs/genética , MicroRNAs/uso terapêutico , Adenocarcinoma , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Esôfago/patologia , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Prognóstico
12.
Cancer Med ; 10(8): 2668-2679, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33710792

RESUMO

Methylation biomarkers are promising tools for diagnosis and disease prevention. The S5 classifier is aimed at the prevention of cervical cancer by the early detection of cervical intraepithelial neoplasia (CIN). S5 is based on pyrosequencing a promoter region of EPB41L3 and five late regions of HPV types 16, 18, 31, and 33 following bisulfite conversion of DNA. Good biomarkers should perform well in a variety of sample types such as exfoliated cells, fresh frozen or formalin-fixed paraffin-embedded (FFPE) materials. Here, we tested the performance of S5 on 315 FFPE biopsies with paired exfoliated cervical samples using four different conversion kits (Epitect Bisulfite, Epitect Fast Bisulfite, EZ DNA Methylation, and EZ DNA Methylation-Lightning). The S5 values from FFPE biopsies for all kits were significantly correlated with those obtained from their paired exfoliated cells. For the EZ DNA Methylation kit, we observed an average increased methylation of 4.4% in FFPE. This was due to incomplete conversion of DNA (73% for FFPE vs. 95% for cells). The other kits had a DNA conversion rate in FFPE similar to the cells (95%-97%). S5 performed well at discriminating

Assuntos
Neoplasia Intraepitelial Cervical/patologia , Metilação de DNA , Neoplasias do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Alphapapillomavirus/genética , Área Sob a Curva , Biópsia/métodos , Neoplasia Intraepitelial Cervical/genética , Colposcopia , Feminino , Formaldeído , Humanos , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Sensibilidade e Especificidade , Sulfitos , Fixação de Tecidos , Neoplasias do Colo do Útero/genética , Adulto Jovem
13.
Cancer Med ; 10(7): 2380-2395, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33694292

RESUMO

OBJECTIVE: Deciphering the determinants of the intralesional immune reaction in cervical carcinogenesis may be conducive to improving the understanding of the disease and then improve outcomes. METHODS: Public gene-expression data and full clinical annotation were searched in Gene Expression Omnibus in the joint analysis of the array-based four eligible cohorts. The infiltrating estimation was quantified using microenvironment cell populations-counter algorithm and absolute-mode CIBERSORT and verified by flow cytometry analysis. An unsupervised classification on immune genes strongly associated with progression, designated by linear mixed-effects regression. We determined immune response and signaling features of the different developmental stages and immune phenotypes by functional annotation and systematically correlated the expression of immune checkpoints with cell-infiltrating characteristics. RESULTS: We identified the lesion-intrinsic immunosuppression mechanism was triggered at precancerous stages, such as genome instability and mutation, aerobic glycolysis, activation of proto-oncogene pathways and so forth. Predominant innate and adoptive cells were increasing from normalcy to cancer (B cell, total T cell, regulatory T cells [Tregs], monocytes, neutrophils, and M2-like macrophages) together with the decrease of CD4+ T cell and CD8+ T cell through the development of cervical cancer. Immune escape initiated on the expression of immunosuppressive molecules from high-grade squamous intraepithelial lesions (HSIL) and culminated in squamous cell carcinoma (SCC). Of note, the expression of immune checkpoints was escalated in the immune-hot and immune-warm phenotype largely encompassed by HSIL and SCC under the stress of both activated and suppressive immune responses. CONCLUSIONS: Immune surveillance is unleashing from low-grade squamous intraepithelial lesions onwards and immune-suppression mechanisms are triggered in HSIL. Thorough knowledge of the immune changing pattern during cervical tumorigenesis contributes to finding the potential therapeutic targets to susceptive patients towards immune checkpoints inhibitors.


Assuntos
Lesões Pré-Cancerosas/imunologia , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/imunologia , Algoritmos , Carcinogênese/imunologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Bases de Dados Genéticas , Progressão da Doença , Feminino , Citometria de Fluxo , Instabilidade Genômica , Glicólise , Humanos , Tolerância Imunológica/genética , Imunidade Celular , Imunofenotipagem , Monitorização Imunológica , Mutação , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Ativação Transcricional , Evasão Tumoral/imunologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
14.
Zhonghua Fu Chan Ke Za Zhi ; 56(2): 114-120, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33631883

RESUMO

Objective: To analyze the characteristics of high-grade squamous intraepithelial lesion (HSIL) diagnosed by cervical tissue sampling in postmenopausal women. Methods: A retrospective study was performed on 2 013 patients with HSIL diagnosed by cervical tissue sampling under colposcopy and treated by cervical conization at the First Affiliated Hospital of Zhengzhou University from June 2017 to November 2018, to compare the difference of patients' clinical features, HPV test, liquid-based thin-layer cytology (TCT), performance of colposcopy and biopsy pathology, pathology after cervical conization between 439 postmenopausal patients and 1 574 pre-menopausal patients. Results: (1) Clinical features: the proportion of contact bleeding showed no significant difference between postmenopausal patients and pre-menopausal patients [4.3% (19/439) vs 6.4% (101/1 574); χ²=2.672, P=0.102]. Among the patients with contact bleeding, the proportion of cervical cancer after cervical cone resection was significantly higher in postmenopausal patients compared with pre-menopausal patients [10/19 vs 22.8% (23/101); χ²=7.157, P=0.007]. Among the patients found by routine screening, the proportion of cervical cancer after cervical cone resection was significantly higher in postmenopausal patients compared with pre-menopausal patients [9.0% (38/420) vs 4.3% (63/1 473); χ²=14.726, P<0.01]. The proportion of smooth cervix was higher in postmenopausal patients compared with pre-menopausal patients [63.6% (279/439) vs 35.5% (558/1 574); χ²=111.601, P<0.01]. (2) High-risk HPV infection: there was no significant difference in the high-risk HPV positive rate between the postmenopausal group and the pre-menopausal group [92.0% (404/439) vs 94.4% (1 486/1 574); χ²=3.394, P=0.065]; the HPV 16 infection was the most common type, but there was no significant difference in the HPV 16 infection rate between the two groups [65.8% (289/439) vs 68.0% (1 070/1 574); χ²=0.722, P=0.395]. (3) TCT test: TCT test results included negative for intraepithelial lesion and malignancy (NILM), atypical squamous cell of undetermined signification (ASCUS), atypical squamous cells cannot exclude high-grade lesion (ASC-H), low grade squamous intraepithelial lesion (LSIL), HSIL, compared with the different results of TCT examination, there were not statistically significant difference between postmenopausal and pre-menopausal patients (all P>0.05). (4) The performance of colposcopy: the proportion of insufficient colposcopy and the proportion of cervical type Ⅲ conversion area were higher in postmenopausal patients compared with pre-menopausal patients [87.5% (384/439) vs 32.5% (511/1 574), P<0.01; 80.0% (351/439) vs 21.9% (344/1 574), P<0.01]. The proportion and positive rate of endocervical curettage (ECC) in postmenopausal patients were higher than those in pre-menopausal patients [35.3% (155/439) vs 20.4% (322/1 574), P<0.01; 67.7% (105/155) vs 53.1% (171/322), P=0.003]. The proportion of lesions involving the vaginal wall was higher in postmenopausal patients compared with pre-menopausal patients [5.9% (26/439) vs 1.0% (16/1 574); χ²=40.443, P<0.01]. There was a positive correlation between vaginal wall lesions and cervical lesions in postmenopausal patients (r=0.660, P<0.01). (5) Postoperative pathology: the positive rate of margin and the proportion of pathological escalation after cervical conization were significantly higher in postmenopausal patients compared with pre-menopausal patients [14.6% (64/439) vs 4.8% (75/1 574), 10.9% (48/439) vs 5.5% (86/1 574); P<0.01]. Conclusions: Colposcopy in postmenopausal women is often inadequate, and the cervix is mostly type Ⅲ transformation zone. The lesion in postmenopausal women is more likely to involve the cervical canal and vaginal wall. Clinical attention should be paid to cervical tube curettage and comprehensive examination of the vaginal wall. The high rate of positive margins and a high proportion of pathological upgrading after cervical conization in postmenopausal patients requires further active intervention.


Assuntos
Biópsia/métodos , Colposcopia/métodos , Pós-Menopausa , Lesões Pré-Cancerosas/epidemiologia , Adulto , Feminino , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Esfregaço Vaginal/métodos
16.
Am J Surg Pathol ; 45(4): 516-522, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560656

RESUMO

We identified an unusual pattern of renal tubular proliferation associated with chronic renal disease, found in 23 patients, diffusely (n=12), or focally (n=11). Incidence was 5% of end-stage renal disease kidneys from one institution (8/177) and 7/23 patients with acquired cystic kidney disease-associated renal cell carcinoma from another. Most (19 patients) had 1 or more neoplasms including papillary (n=9), acquired cystic kidney disease (n=8), clear cell (n=4), or clear cell papillary (n=3) renal cell carcinoma. All (20 men, 3 women) had end-stage renal disease. The predominant pattern (n=18) was the indentation of chronic inflammation into renal tubules forming small polypoid structures; however, 5 had predominantly hyperplastic epithelium with less conspicuous inflammation. In 14 patients both patterns were appreciable, whereas the remainder had only the inflammatory pattern. Immunohistochemistry was positive for cytokeratin 7, high-molecular-weight cytokeratin, PAX8, and GATA3. Staining for alpha-methylacyl-CoA racemase was negative or weak, dramatically less intense than papillary neoplasms or proximal tubules. CD3 and CD20 showed a mixture of B and T lymphocytes in the inflammatory areas. Fluorescence in situ hybridization showed no trisomy 7 or 17 or loss of Y (n=9). We describe a previously uncharacterized form of renal tubular proliferation that differs from papillary adenoma (with weak or negative alpha-methylacyl-CoA racemase, lack of trisomy 7 or 17, and sometimes diffuse distribution). On the basis of consistent staining for high-molecular-weight cytokeratin and GATA3, we propose the name distal tubular hyperplasia for this process. Future studies will be helpful to assess preneoplastic potential and etiology.


Assuntos
Adenoma/patologia , Carcinoma de Células Renais/patologia , Proliferação de Células , Doenças Renais Císticas/patologia , Falência Renal Crônica/patologia , Neoplasias Renais/patologia , Túbulos Renais/patologia , Lesões Pré-Cancerosas/patologia , Adenoma/química , Adenoma/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/química , Carcinoma de Células Renais/genética , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , Neoplasias Renais/química , Neoplasias Renais/genética , Túbulos Renais/química , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Valor Preditivo dos Testes , Estados Unidos , Adulto Jovem
18.
J Gastroenterol Hepatol ; 36(1): 20-24, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33448515

RESUMO

White-light endoscopy with biopsy is the current gold standard modality for detecting and diagnosing upper gastrointestinal (GI) pathology. However, missed lesions remain a challenge. To overcome interobserver variability and learning curve issues, artificial intelligence (AI) has recently been introduced to assist endoscopists in the detection and diagnosis of upper GI neoplasia. In contrast to AI in colonoscopy, current AI studies for upper GI endoscopy are smaller pilot studies. Researchers currently lack large volume, well-annotated, high-quality datasets in gastric cancer, dysplasia in Barrett's esophagus and early esophageal squamous cell cancer. This review will look at the latest studies of AI in upper GI endoscopy, discuss some of the challenges facing researchers, and predict what the future may hold in this rapidly changing field.


Assuntos
Inteligência Artificial/tendências , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/tendências , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Previsões , Gastrite/diagnóstico , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter , Humanos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia
19.
Virchows Arch ; 479(1): 179-189, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33511431

RESUMO

Cystic lesions of the pancreas may range from benign to precursors of pancreatic cancer. Simple mucinous cyst (SMC) is larger than 1 cm, has a gastric-type flat mucinous lining, and minimal atypia without ovarian-type stroma. We report a new case of pancreatic SMC, coupling a systematic review of the English literature mainly focused on their clinic-pathological features. We reviewed 103 cases of SMC in adults (73 women), averaging 57 (range, 26-70) years. The SMCs were located in the body-tail region of the pancreas in 60 (58%) cases, presenting as single cystic lesions in 94% of cases; 43% of patients were asymptomatic. A preoperative fine-needle aspiration of the cyst fluid detected amylase and carcinoembryonic antigen positivity in 71% and 76% of cases, respectively. Patients underwent surgery mostly for suspected malignancy; in 83% of cases, a standard pancreatic resection was performed. Mean SMC size was 4.9 (range, 1.5-12.0) cm. Mucins MUC5AC and MUC6 resulted positive in 77% and 81% of cases performed, respectively, whereas MUC2 was negative in all but one patient. The SMC from our institution was characterized by a KRAS somatic mutation. The diagnosis of SMC should be considered when a solitary pancreatic cyst larger than 1 cm is detected in asymptomatic patients. To establish a correct diagnosis, an extensive histologic/immunohistochemical analysis is essential. The presence of a KRAS mutation highlights that SMC may represent another potential pancreatic cancer precursor.


Assuntos
Biomarcadores Tumorais/análise , Cistadenoma Mucinoso/patologia , Mucina-5AC/análise , Mucina-6/análise , Cisto Pancreático/patologia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Amilases/análise , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/análise , Cistadenoma Mucinoso/genética , Cistadenoma Mucinoso/metabolismo , Cistadenoma Mucinoso/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pancreatectomia , Cisto Pancreático/química , Cisto Pancreático/genética , Cisto Pancreático/cirurgia , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Intraductais Pancreáticas/metabolismo , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/cirurgia , Proteínas Proto-Oncogênicas p21(ras)/genética
20.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443161

RESUMO

Fluorescence imaging is currently being actively developed for surgical guidance; however, it remains underutilized for diagnostic and endoscopic surveillance of incipient colorectal cancer in high-risk patients. Here we demonstrate the utility and potential for clinical translation of a fluorescently labeled cathepsin-activated chemical probe to highlight gastrointestinal lesions. This probe stays optically dark until it is activated by proteases produced by tumor-associated macrophages and accumulates within the lesions, enabling their detection using an endoscope outfitted with a fluorescence detector. We evaluated the probe in multiple murine models and a human-scale porcine model of gastrointestinal carcinogenesis. The probe provides fluorescence-guided surveillance of gastrointestinal lesions and augments histopathological analysis by highlighting areas of dysplasia as small as 400 µm, which were visibly discernible with significant tumor-to-background ratios, even in tissues with a background of severe inflammation and ulceration. Given these results, we anticipate that this probe will enable sensitive fluorescence-guided biopsies, even in the presence of highly inflamed colorectal tissue, which will improve early diagnosis to prevent gastrointestinal cancers.


Assuntos
Detecção Precoce de Câncer/métodos , Endoscopia/métodos , Lesões Pré-Cancerosas/diagnóstico , Animais , Colo/patologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Feminino , Fluorescência , Corantes Fluorescentes , Neoplasias Gastrointestinais/patologia , Trato Gastrointestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Imagem Molecular/métodos , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Endogâmicos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/prevenção & controle , Suínos
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