Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 305
Filtrar
1.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474205

RESUMO

Pulmonary adenocarcinoma (ADC) is a very diverse disease, both genetically and histologically, which displays extensive intratumor heterogeneity with numerous acquired mutations. ADC is the most common type of lung cancer and is believed to arise from adenocarcinoma in situ (AIS) which then progresses to minimally invasive adenocarcinoma (MIA). In patients of European ethnicity, we analyzed genetic mutations in AIS (n = 10) and MIA (n = 18) and compared the number of genetic mutations with advanced ADC (n = 2419). Using next-generation sequencing, the number of different mutations detected in both AIS (87.5%) and MIA (94.5%) were higher (p < 0.001) than in advanced ADC (53.7%). In contrast to the high number of mutations in Kirsten rat sarcoma virus gene (KRAS) in advanced ADC (34.6%), there was only one case of AIS with KRAS G12C mutation (3.5%; p < 0.001) and no cases of MIA with KRAS mutation (p < 0.001). In contrast to the modest prevalence of epidermal growth factor receptor (EGFR) mutations in advanced ADC (15.0%), the fraction of EGFR mutant cases was higher in both in AIS (22.2%) and MIA (59.5%; p < 0.001). The EGFR exon 19 deletion mutation was more common in both MIA (50%; n = 6/12) and ADC (41%; n = 149/363), whereas p.L858R was more prevalent in AIS (75%; n = 3/4). In contrast to pulmonary advanced ADC, KRAS driver mutations are less common, whereas mutations in EGFR are more common, in detectable AIS and MIA.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma in Situ/genética , Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma/patologia , Neoplasias Pulmonares/metabolismo , Mutação , Receptores ErbB/metabolismo
2.
Zhongguo Fei Ai Za Zhi ; 27(2): 118-125, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38453443

RESUMO

BACKGROUND: The pathological types of lung ground glass nodules (GGNs) show great significance to the clinical treatment. This study was aimed to predict pathological types of GGNs based on computed tomography (CT) quantitative parameters. METHODS: 389 GGNs confirmed by postoperative pathology were selected, including 138 cases of precursor glandular lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], 109 cases of microinvasive adenocarcinoma (MIA) and 142 cases of invasive adenocarcinoma (IAC). The morphological characteristics of nodules were evaluated subjectively by radiologist, as well as artificial intelligence (AI). RESULTS: In the subjective CT signs, the maximum diameter of nodule and the frequency of spiculation, lobulation and pleural traction increased from AAH+AIS, MIA to IAC. In the AI quantitative parameters, parameters related to size and CT value, proportion of solid component, energy and entropy increased from AAH+AIS, MIA to IAC. There was no significant difference between AI quantitative parameters and the subjective CT signs for distinguishing the pathological types of GGNs. CONCLUSIONS: AI quantitative parameters were valuable in distinguishing the pathological types of GGNs.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Humanos , Neoplasias Pulmonares/patologia , Inteligência Artificial , Estudos Retrospectivos , Invasividade Neoplásica , Adenocarcinoma/patologia , Adenocarcinoma in Situ/patologia , Tomografia Computadorizada por Raios X/métodos , Lesões Pré-Cancerosas/patologia , Hiperplasia , Pulmão/diagnóstico por imagem , Pulmão/patologia
3.
Colloids Surf B Biointerfaces ; 236: 113824, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431997

RESUMO

Exosomes, extracellular vesicles released by cells, hold potential as diagnostic markers for the early detection of lung cancer. Despite their clinical promise, current technologies lack rapid and effective means to discriminate between exosomes derived from adenocarcinoma in situ (AIS) and early-stage invasive adenocarcinoma (IAC). This challenge arises from the intrinsic structural heterogeneity of exosomes, necessitating the development of advanced methodologies for precise differentiation. Here, we demonstrate a novel approach for plasma exosome detection utilizing multi-receptor surface-enhanced Raman spectroscopy (SERS) technology to differentiate between AIS and early-stage IAC. To accomplish this, we synthesized a stable and uniform two-dimensional SERS substrate (BC/Au NPs film) by fabricating gold nanoparticles onto bacterial cellulose. We then enhanced its capabilities by introducing multi-receptor SERS functionality via modifying the substrate with both low-specificity and physicochemical-selective molecules. Furthermore, by strategically combining all capturer-exosome SERS spectra, comprehensive "combined-SERS spectra" are reconstructed to enhance spectral variations of the exosome. Combining these features with partial least squares regression-discriminant analysis (PLS-DA) modeling significantly improved discriminatory accuracy, achieving 90% sensitivity and 95% specificity in distinguishing AIS from early-stage IAC. Our developed SERS sensor provides an effective method for early detection of lung cancer, thereby paving a new way for innovative advancements in diagnosing lung cancer.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Exossomos , Neoplasias Pulmonares , Nanopartículas Metálicas , Humanos , Exossomos/química , Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Neoplasias Pulmonares/diagnóstico
4.
Am J Surg Pathol ; 48(4): 475-486, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38298022

RESUMO

Serous tubal intraepithelial carcinoma (STIC) is the fallopian tube precursor lesion for most cases of pelvic high-grade serous carcinoma (HGSC). To date, the morphologic, molecular, and clinical heterogeneity of STIC and a less atypical putative precursor lesion, termed serous tubal intraepithelial lesion, has not been well characterized. Better understanding of precursor heterogeneity could impact the clinical management of women with incidental STICs (without concurrent carcinoma) identified in cases of prophylactic or opportunistic salpingectomy. This study analyzed morphologic and molecular features of 171 STICs and 21 serous tubal intraepithelial lesions. We assessed their histologic features, Ki-67 and p53 staining patterns, and genome-wide DNA copy number alterations. We classified all precursor lesions into 2 morphologic subtypes, one with a flat surface (Flat) and the other characterized by budding, loosely adherent, or detached (BLAD) morphology. On the basis of pathology review by a panel of 8 gynecologic pathologists, we found 87 BLAD, 96 Flat, and 9 indeterminate lesions. As compared with Flat lesions, BLAD lesions were more frequently diagnostic of STIC ( P <0.0001) and were found concurrently with HGSC ( P <0.0001). BLAD morphology was also characterized by higher Ki-67 proliferation index ( P <0.0001), presence of epithelial stratification ( P <0.0001), and increased lymphocyte density ( P <0.0001). BLAD lesions also exhibited more frequent DNA copy number gain/amplification at the CCNE1 or CMYC loci canonical to HGSCs ( P <0.0001). Both BLAD morphology and STIC diagnoses are independent risk factors for an elevated Ki-67 proliferation index. No correlation was observed between BLAD and Flat lesions with respect to patient age, presence of germline BRCA1/2 mutation, or p53 staining pattern. These findings suggest that tubal precursor lesions are morphologically and molecularly heterogeneous, laying the foundation for further studies on the pathogenesis of HGSC initiation and identifying histologic features predictive of poor patient outcomes.


Assuntos
Adenocarcinoma in Situ , Carcinoma in Situ , Carcinoma , Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Feminino , Humanos , Proteína BRCA1 , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Neoplasias Ovarianas/patologia , Antígeno Ki-67 , Proteína Supressora de Tumor p53/genética , Proteína BRCA2 , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , DNA
5.
Pathol Res Pract ; 254: 155062, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199133

RESUMO

HPV-independent in situ adenocarcinomas have been only recently added to the WHO 2020 classification. To date, little information has been published about HPVindependent precursor lesions. In particular, regardiong the extremely rare cervical endometrioid type adenocarcinoma thought to arise in the setting of cervical endometriosis, a premalignant lesion is still not well defined. In this short communication we describe a possible precursor to invasive cervical endometrioid type adenocarcinoma in a 39-yr-old patient, with a previous history of breast cancer.


Assuntos
Adenocarcinoma in Situ , Carcinoma Endometrioide , Neoplasias do Colo do Útero , Feminino , Humanos , Colo do Útero/patologia , Adenocarcinoma in Situ/patologia , Carcinoma Endometrioide/patologia , Neoplasias do Colo do Útero/patologia
7.
J Low Genit Tract Dis ; 28(2): 149-152, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38251975

RESUMO

OBJECTIVES: Evaluation of the results of treatment of adenocarcinoma in situ by loop electrosurgical excision procedure and the safety of a conservative strategy. METHODS: Identification of all cases of adenocarcinoma in situ treated by loop electrosurgical excision procedure at our institution and follow-up by a conservative strategy. Completeness of the identification of all cases was secured by data from the National Pathology Registry. The treatment strategy was based on cytologic follow-up performed by a general practitioner and, irrespective of margin status of the cone, only the results of the postoperative surveillance were indicative of further treatment. RESULTS: A total of 224 patients were identified. The overall recurrence rate with a mean follow-up time of 87.8 months was 7.6% (17/224). The recurrence rate in patients with involved margins was significantly higher than in patients with uninvolved margins, 15.7% vs 5.2%, respectively. Six recurrences were diagnosed at first examination 6 months postconization in patients with involved margins. They were treated with hysterectomy in 4 cases and reconization in 1 case. If involvement of margins alone had been an indication of further therapy (hysterectomy or reconization) immediately after conization, the conservative management strategy prevented 46 surgical procedures. Two cases of invasive cancer were diagnosed during follow-up, 150 months and 196 months after primary treatment, and after normal follow-up examinations. These 2 cases must be considered de novo cases and cannot be considered treatment failures. CONCLUSION: The conservative management strategy thus seems safe, and unnecessary surgical procedures were avoided.


Assuntos
Adenocarcinoma in Situ , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Adenocarcinoma in Situ/cirurgia , Adenocarcinoma in Situ/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Eletrocirurgia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Conização/métodos , Displasia do Colo do Útero/cirurgia
9.
Lancet Respir Med ; 12(2): 141-152, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042167

RESUMO

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Fumantes , Estudos Prospectivos , Detecção Precoce de Câncer/métodos , Taiwan/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Programas de Rastreamento
10.
J Low Genit Tract Dis ; 28(1): 37-42, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37963327

RESUMO

OBJECTIVES/PURPOSE: The reproducibility and sensitivity of image-based colposcopy is low, but agreement on lesion presence and location remains to be explored. Here, we investigate the interobserver agreement on lesions on colposcopic images by evaluating and comparing marked lesions on digitized colposcopic images between colposcopists. METHODS: Five colposcopists reviewed images from 268 colposcopic examinations. Cases were selected based on histologic diagnosis, i.e., normal/cervical intraepithelial neoplasia (CIN)1 ( n = 50), CIN2 ( n = 50), CIN3 ( n = 100), adenocarcinoma in situ ( n = 53), and cancer ( n = 15). We obtained digitized time-series images every 7-10 seconds from before acetic acid application to 2 minutes after application. Colposcopists were instructed to digitally annotate all areas with acetowhitening or suspect of lesions. To estimate the agreement on lesion presence and location, we assessed the proportion of images with annotations and the proportion of images with overlapping annotated area by at least 4 (4+) colposcopists, respectively. RESULTS: We included images from 241 examinations (1 image from each) with adequate annotations. The proportion with a least 1 lesion annotated by 4+ colposcopists increased by severity of histologic diagnosis. Among the CIN3 cases, 84% had at least 1 lesion annotated by 4+ colposcopists, whereas 54% of normal/CIN1 cases had a lesion annotated. Notably, the proportion was 70% for adenocarcinoma in situ and 71% for cancer. Regarding lesion location, there was no linear association with severity of histologic diagnosis. CONCLUSION: Despite that 80% of the CIN2 and CIN3 cases were annotated by 4+ colposcopists, we did not find increasing agreement on lesion location with histology severity. This underlines the subjective nature of colposcopy.


Assuntos
Adenocarcinoma in Situ , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Gravidez , Humanos , Colposcopia/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Reprodutibilidade dos Testes , Displasia do Colo do Útero/patologia
11.
Histopathology ; 84(2): 369-380, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37920148

RESUMO

AIMS: The invasive pattern in HPV-associated endocervical adenocarcinoma (HPVA) has prognostic value. Non-destructive (pattern A) HPVA has excellent prognosis mirroring adenocarcinoma in-situ (AIS). However, the rare occurrence of ovarian spread in these tumours suggests aggressiveness in a subset of patients with these otherwise indolent lesions. We hypothesise that AIS/pattern A HPVA with ovarian metastases are biologically different than metastatic destructively invasive HPVA. METHODS AND RESULTS: Samples from patients with HPVA and synchronous or metachronous metastases were retrieved and reviewed to confirm diagnosis and determine the Silva pattern in the primary lesion. For each case, normal tissue, cervical tumour and at least one metastasis underwent comprehensive sequencing using a 447-gene panel. Pathogenic single-nucleotide variants and segmental copy-number alterations (CNA), tumour mutational burden and molecular signatures were evaluated and compared between primary and metastases and among invasive pattern categories. We identified 13 patients: four had AIS/pattern A primaries, while nine had pattern B/C tumours. All AIS/pattern A lesions had metastasis only to ovary; 50% of patients with ovarian involvement, regardless of invasive pattern, also had involvement of the endometrium and/or fallopian tube mucosa by HPVA. In the ovary, AIS/pattern A HPVA showed deceptive well-differentiated glands, often with adenofibroma-like appearance. Conversely, pattern C HPVAs consistently showed overt infiltrative features in the ovary. Sequencing confirmed the genetic relationship between primary and metastatic tumours in each case. PIK3CA alterations were identified in three of four AIS/pattern A HPVAs and three of eight pattern B/C tumours with sequenced metastases. Pattern C tumours showed a notably higher number of CNA in primary tumours compared to pattern A/B tumours. Only one metastatic AIS/pattern A HPVA had a novel pathogenic variant compared to the primary. Conversely, five of eight pattern B/C tumours with sequenced metastases developed novel pathogenic variants in the metastasis not seen in the primary. All four AIS/pattern A patients were alive and free of disease at 31, 47, 58 and 212 months after initial diagnosis. Conversely, cancer-related death was documented in five of nine pattern B/C patients with follow-up at 7, 20, 20, 43 and 87 months. CONCLUSION: Morphologically and genomically, AIS/pattern A HPVA with secondary ovarian involvement appears distinct from destructively invasive tumours. In at least a subset of these cases, ovarian spread appears to occur via trans-Mullerian superficial extension, different from the stromal and lymphatic vascular spread typical of more aggressive tumours (pattern C). These differences may explain the indolent outcome observed in the rare subset of patients with AIS/pattern A HPVA and ovarian metastasis. Our data underscore the potential for conservative surgical management approaches to pattern A HPVA.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Neoplasias Ovarianas , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/diagnóstico , Infecções por Papillomavirus/complicações , Adenocarcinoma/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/secundário
12.
AJR Am J Roentgenol ; 222(1): e2329674, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37493322

RESUMO

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Aprendizado Profundo , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Invasividade Neoplásica/patologia , Adenocarcinoma/patologia , Pulmão/patologia , Adenocarcinoma in Situ/patologia , Tomografia Computadorizada por Raios X/métodos , Hiperplasia/patologia , Lesões Pré-Cancerosas/patologia
13.
Nat Commun ; 14(1): 8375, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102134

RESUMO

The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Pulmão/patologia , Adenocarcinoma in Situ/genética , Mutação , Microambiente Tumoral
14.
Sci Rep ; 13(1): 16144, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752238

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), a highly lethal disease with limited therapeutic options, may benefit from repurposing of FDA-approved drugs in preventive or interceptive strategies in high-risk populations. Previous animal studies demonstrated that the use of metformin and statins as single agents at relatively high doses restrained PDAC development. Here, four-week-old mice expressing KrasG12D in all pancreatic lineages (KC mice) and fed an obesogenic high fat, high calorie diet that promotes early PDAC development were randomized onto low dosage metformin, simvastatin, or both drugs in combination administered orally. Dual treatment attenuated weight gain, fibro-inflammation, and development of advanced PDAC precursor lesions (pancreatic intraepithelial neoplasia [PanIN]-3) in male KC mice, without significant effect in females or when administered individually. Dual-treated KC mice had reduced proliferation of PanIN cells and decreased transcriptional activity of the Hippo effectors, YAP and TAZ, which are important regulators of PDAC development. Metformin and simvastatin also synergistically inhibited colony formation of pancreatic cancer cells in vitro. Together, our data demonstrated that a combination of low doses of metformin and simvastatin inhibits PDAC development and imply that both drugs are promising agents for being tested in clinical trials for preventing pancreatic cancer progression.


Assuntos
Adenocarcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Masculino , Feminino , Animais , Camundongos , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/prevenção & controle , Obesidade/complicações , Obesidade/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/prevenção & controle , Neoplasias Pancreáticas
15.
Mod Pathol ; 36(12): 100326, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37678674

RESUMO

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials from ADC precursors. Here, we employed state-of-the-art deep learning and artificial intelligence techniques to robustly segment and recognize cells on routinely used hematoxylin and eosin histopathology images and extracted 9 biology-relevant pathomic features to decode lung preneoplasia evolution. We analyzed 3 distinct cohorts (Japan, China, and United States) covering 98 patients, 162 slides, and 669 regions of interest, including 143 normal, 129 atypical adenomatous hyperplasia, 94 AIS, 98 MIA, and 205 ADC. Extracted pathomic features revealed progressive increase of atypical epithelial cells and progressive decrease of lymphocytic cells from normal to AAH, AIS, MIA, and ADC, consistent with the results from tissue-consuming and expensive molecular/immune profiling. Furthermore, pathomics analysis manifested progressively increasing cellular intratumor heterogeneity along with the evolution from normal lung to invasive ADC. These findings demonstrated the feasibility and substantial potential of pathomics in studying lung cancer carcinogenesis directly from the low-cost routine hematoxylin and eosin staining.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Humanos , Hiperplasia/patologia , Inteligência Artificial , Amarelo de Eosina-(YS) , Hematoxilina , Adenocarcinoma/genética , Adenocarcinoma/patologia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adenocarcinoma in Situ/genética , Adenocarcinoma in Situ/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Evolução Molecular , Carcinogênese/patologia
16.
Ann Surg Oncol ; 30(12): 7400-7411, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37658270

RESUMO

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Lesões Pré-Cancerosas , Humanos , Antígeno B7-H1/metabolismo , Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/cirurgia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Adenocarcinoma in Situ/genética , Adenocarcinoma in Situ/cirurgia , Hiperplasia
17.
Acta Cytol ; 67(6): 604-617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37562375

RESUMO

INTRODUCTION: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions. METHODS: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined. RESULTS: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017). CONCLUSION: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.


Assuntos
Adenocarcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Teste de Papanicolaou , Esfregaço Vaginal , Hiperplasia/patologia , Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adenocarcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Metaplasia/patologia , Inflamação/patologia
18.
J Gynecol Obstet Hum Reprod ; 52(7): 102622, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37321399

RESUMO

OBJECTIVE: Excisional procedures have a central role in the management of adenocarcinoma in situ of the cervix (AIS). We aimed to evaluate the relationship between the excisional specimen dimensions and the endocervical margin status. METHODS: We conducted a multicentric retrospective study in seven French centers. All cases with proven AIS on a colposcopic biopsy and undergoing an excisional procedure afterwards were included in the analysis. We evaluated the impact of excision length, along with the lateral and anteroposterior diameters on the endocervical margin status. An additional subgroup analysis of the impact of maternal age on endocervical margin status was also conducted. RESULTS: Of the 101 cases of AIS diagnosed on initial biopsy, 95 underwent a primary excisional procedure, among which 80% (n = 76/95) had uninvolved endocervical margins and 20% (n = 19/95) had positive endocervical margins. The excisional specimen length was not significantly related to the endocervical margin status. Conversely, both lateral and antero-posterior diameters were significantly correlated with the negative endocervical margins status: OR = 1,19, 95% CI [1.03, 1.40], p = 0.025, for the lateral diameter and OR = 1.34, 95% CI [1.14, 1.64], p = 0.001 for the antero-posterior diameter. The median lateral diameter was 20 mm, IQR (18, 24) in case of endocervical negative margins vs. 18 mm IQR (15, 24) in case of positive endocervical margins (p = 0.039), and the median anteroposterior diameter was 17 mm IQR (15, 20) in case of negative endocervical margins vs 14 mm IQR (11, 15) in case of positive endocervical margins (p = 0.004), respectively.  Additionally, in patients over 45 years old, endocervical margin were more likely to be positive despite similar excisional dimensions (7/17 (41%) of positive endocercival margins before 45 years old vs 12/78 (15%) after, p = 0.039) CONCLUSIONS: Endocervical margin statues were significantly related to the transverse diameters (lateral and anteroposterior diameters), but not to the excision specimen length. Reducing the excised length may lead to fewer post-procedure complications but would still allow to obtain a large proportion of negative endocervical margins.


Assuntos
Adenocarcinoma in Situ , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Colo do Útero/cirurgia , Colo do Útero/patologia , Adenocarcinoma in Situ/cirurgia , Adenocarcinoma in Situ/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Conização , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Margens de Excisão
19.
J Obstet Gynaecol Can ; 45(10): 102171, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37343621

RESUMO

OBJECTIVES: (1) To determine the role of human papillomavirus (HPV) testing after excisional treatment of cervical precancer. (2) To determine clinical factors associated with persistence of cervical precancer post-treatment. METHODS: A retrospective chart review was conducted including patients who had a loop electrosurgical excision procedure (LEEP) for cervical precancer (cervical intraepithelial neoplasia 3/adenocarcinoma in situ/high-grade squamous intraepithelial lesions [HSIL]). All patients treated between 2016 and 2018 at a tertiary centre colposcopy unit were included. Persistence/recurrence of disease was defined as high-grade cytology or histology identified during the time of follow-up. Univariate and multivariate regression models were performed to identify factors associated with persistence/recurrence and HPV positivity at exit testing. RESULTS: A total of 284 patients were included. The median follow-up time was 19 months. Of the LEEP specimens, 90.8% (n = 258) demonstrated HSIL and 3.9% (n = 11) had adenocarcinoma in situ. 28.5% (n = 81) of the LEEP specimens had positive margins. In follow-up, 72.9% had negative cytology, 17.6% had atypical squamous cells of undetermined significance/low-grade SIL, 1.8% had atypical squamous cells, HSIL cannot be excluded/low-grade SIL-H, and 6.7% had HSIL. At the final follow-up, 27.8% (n = 79) were HPV+. Overall rate of persistence/recurrence was 11.3% (n = 32); median time to persistence/recurrence was 6.5 months. Multivariate regression models demonstrated that follow-up HPV positivity (OR = 22.0) and positive margins (OR = 3.7) were significantly associated with persistence/recurrence. Similarly, in univariate regression models, positive margins were significant (OR = 2.2) for predicting HPV positivity in exit testing. CONCLUSIONS: Persistence/recurrence of precancer can occur due to incomplete treatment of lesions by local excision and by the persistence of HPV infection. Surveillance strategies for women treated for cervical precancer require a risk-based approach and should rely on HPV testing.


Assuntos
Adenocarcinoma in Situ , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Estudos Retrospectivos , Displasia do Colo do Útero/patologia , Margens de Excisão
20.
Kyobu Geka ; 76(5): 352-355, 2023 May.
Artigo em Japonês | MEDLINE | ID: mdl-37150913

RESUMO

We report a rare case of positive findings in pleural lavage cytology(PLC) in the patient with pulmonary adenocarcinoma in situ (AIS). A 78-year-old woman was presented with a 30 mm pure groundglass nodule (GGN) in the left upper lobe on chest computed tomography (CT). After 2 years follow- up, thoracoscopic surgery was performed to resect the nodule. PLC was performed before pulmonary resection. Histopathological diagnosis was 25 mm AIS. However, PLC showed positive findings of malignant cells. CT examination at 1 year and 6 months postoperatively showed pleural dissemination findings and the patient died of lung cancer at 3 years and 2 months postoperatively. PLC's contribution to TNM staging has not yet been clarified. The positive findings in PLC and large size of pure GGN were considered likely to be poor prognostic indicators.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Irrigação Terapêutica , Adenocarcinoma in Situ/patologia , Citologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Estadiamento de Neoplasias
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...