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1.
Sci Rep ; 13(1): 1028, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658301

RESUMO

We aimed to investigate the value of computed tomography (CT)-based radiomics with artificial intelligence (AI) in predicting pathological lymph node metastasis (pN) in patients with clinical stage 0-IA non-small cell lung cancer (c-stage 0-IA NSCLC). This study enrolled 720 patients who underwent complete surgical resection for c-stage 0-IA NSCLC, and were assigned to the derivation and validation cohorts. Using the AI software Beta Version (Fujifilm Corporation, Japan), 39 AI imaging factors, including 17 factors from the AI ground-glass nodule analysis and 22 radiomics features from nodule characterization analysis, were extracted to identify factors associated with pN. Multivariate analysis showed that clinical stage IA3 (p = 0.028), solid-part size (p < 0.001), and average solid CT value (p = 0.033) were independently associated with pN. The receiver operating characteristic analysis showed that the area under the curve and optimal cut-off values of the average solid CT value relevant to pN were 0.761 and -103 Hounsfield units, and the threshold provided sensitivity, specificity, and negative predictive values of 69%, 65%, and 94% in the entire cohort, respectively. Measuring the average solid-CT value of tumors for pN may have broad applications such as guiding individualized surgical approaches and postoperative treatment.


Assuntos
Carcinoma in Situ , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Inteligência Artificial , Estadiamento de Neoplasias , Pulmão/patologia , Carcinoma in Situ/patologia , Estudos Retrospectivos
2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614194

RESUMO

Survival from pancreatic cancer is poor because most cancers are diagnosed in the late stages and there are no therapies to prevent the progression of precancerous pancreatic intraepithelial neoplasms (PanINs). Inhibiting mutant KRASG12D, the primary driver mutation in most human pancreatic cancers, has been challenging. The cholecystokinin-B receptor (CCK-BR) is absent in the normal pancreas but becomes expressed in high grade PanIN lesions and is over-expressed in pancreatic cancer making it a prime target for therapy. We developed a biodegradable nanoparticle polyplex (NP) that binds selectively to the CCK-BR on PanINs and pancreatic cancer to deliver gene therapy. PanIN progression was halted and the pancreas extracellular matrix rendered less carcinogenic in P48-Cre/LSL-KrasG12D/+ mice treated with the CCK-BR targeted NP loaded with siRNA to mutant Kras. The targeted NP also slowed proliferation, decreased metastases and improved survival in mice bearing large orthotopic pancreatic tumors. Safety and toxicity studies were performed in immune competent mice after short or long-term exposure and showed no off-target toxicity by histological or biochemical evaluation. Precision therapy with target-specific NPs provides a novel approach to slow progression of advanced pancreatic cancer and also prevents the development of pancreatic cancer in high-risk subjects without toxicity to other tissues.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Camundongos , Humanos , Animais , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Modelos Animais de Doenças , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/prevenção & controle , Pâncreas/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma in Situ/genética , Carcinoma Ductal Pancreático/patologia
5.
Eur J Cancer ; 180: 99-107, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592508

RESUMO

BACKGROUND AND AIMS: The association between smoking and gallbladder cancer (GBC) risk is unclear. We investigated the association between smoking (including pack-years) and GBC risk. We also examined the combined effects of smoking and diabetes or prediabetes on GBC risk. METHODS: This Korean nationwide cohort study included 9,520,629 adults without cancer who underwent national health screening in 2009 and were followed-up until 2018. Multivariable Cox proportional hazards models were used to determine risk estimates after adjusting for potential confounders. RESULTS: During 78.4 million person-years (mean 8.2 ± 0.9 years) of follow-up, we identified 6066 patients with newly diagnosed GBC. Current and former smokers were associated with increased GBC risk (hazard ratio [HR], 95% confidence interval [CI]: 1.117, 1.029-1.212 and 1.105, 1.016-1.202, respectively). Smoking of 20 to <30 and ≥30 pack-years was independently associated with increased GBC risk compared with never smoking (HR, 95% CI; 1.241, 1.100-1.400 and 1.231, 1.107-1.370, respectively). However, smoking of <10 and 10 to <20 pack-years was not. This threshold dose-response association between smoking pack-years and GBC risk was observed regardless of the glycaemic status (all P < 0.01). Furthermore, smoking of ≥20 pack-years and hyperglycaemia had a synergistic effect on the GBC risk (all P < 0.01). Smokers with ≥20 pack-years with diabetes had the highest risk of GBC compared to never smokers with normoglycaemia (HR, 1.658; 95% CI, 1.437-1.914). CONCLUSIONS: Smoking was associated with increased GBC risk with a threshold dose-response effect for smoking pack-years. The risk of GBC increases synergistically when smoking and hyperglycaemia coexist. More individualised cancer prevention education is required to reduce GBC risk.


Assuntos
Carcinoma in Situ , Diabetes Mellitus , Neoplasias da Vesícula Biliar , Hiperglicemia , Adulto , Humanos , Fumar/efeitos adversos , Fumar/epidemiologia , Estudos de Coortes , Fatores de Risco , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/etiologia , Modelos de Riscos Proporcionais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Hiperglicemia/complicações , Hiperglicemia/epidemiologia
6.
Curr Oncol ; 30(1): 959-966, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36661722

RESUMO

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Doença de Paget Extramamária , Lesões Pré-Cancerosas , Neoplasias Vulvares , Feminino , Humanos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/epidemiologia , Doença de Paget Extramamária/terapia , Estudos Retrospectivos , Vulva/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/terapia , Lesões Pré-Cancerosas/complicações , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/terapia , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia
8.
World J Surg Oncol ; 21(1): 6, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641472

RESUMO

BACKGROUND: Disseminated disease (DD) is often found at (re-)exploration in gallbladder cancer (GBC) patients. We aimed to assess the yield of staging laparoscopy (SL) and identify predictors for DD. METHODS: This retrospective study included patients from all Dutch academic centres with primary GBC (pGBC) and incidentally diagnosed GBC (iGBC) planned for (re-)resection. The yield of SL was determined. In iGBC, predictive factors for DD were assessed. RESULTS: In total, 290 patients were included. Of 183 included pGBC patients, 143 underwent laparotomy without SL, and 42 (29%) showed DD perioperatively. SL, conducted in 40 patients, identified DD in eight. DD was found in nine of 32 patients who underwent laparotomy after SL. Of 107 included iGBC patients, 100 underwent laparotomy without SL, and 19 showed DD perioperatively. SL, conducted in seven patients, identified DD in one. Cholecystitis (OR = 4.25; 95% CI 1.51-11.91) and primary R1/R2 resection (OR = 3.94; 95% CI 1.39-11.19) were independent predictive factors for DD. CONCLUSIONS: In pGBC patients, SL may identify DD in up to 20% of patients and should be part of standard management. In iGBC patients, SL is indicated after primary resection for cholecystitis and after initial R1/R2 resection due to the association of these factors with DD.


Assuntos
Carcinoma in Situ , Colecistite , Neoplasias da Vesícula Biliar , Laparoscopia , Humanos , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Estudos de Coortes , Estudos Retrospectivos , Estadiamento de Neoplasias , Colecistite/cirurgia , Carcinoma in Situ/cirurgia
9.
Nat Commun ; 13(1): 7466, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463242

RESUMO

In situ vaccination is a promising strategy to convert the immunosuppressive tumor microenvironment into an immunostimulatory one with limited systemic exposure and side effect. However, sustained clinical benefits require long-term and multidimensional immune activation including innate and adaptive immunity. Here, we develop a probiotic food-grade Lactococcus lactis-based in situ vaccination (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand. Intratumoural delivery of FOLactis contributes to local retention and sustained release of therapeutics to thoroughly modulate key components of the antitumour immune response, such as activation of natural killer cells, cytotoxic T lymphocytes, and conventional-type-1-dendritic cells in the tumors and tumor-draining lymph nodes. In addition, intratumoural administration of FOLactis induces a more robust tumor antigen-specific immune response and superior systemic antitumour efficacy in multiple poorly immune cell-infiltrated and anti-PD1-resistant tumors. Specific depletion of different immune cells reveals that CD8+ T and natural killer cells are crucial to the in situ vaccine-elicited tumor regression. Our results confirm that FOLactis displays an enhanced antitumour immunity and successfully converts the 'cold' tumors to 'hot' tumors.


Assuntos
Carcinoma in Situ , Lactococcus lactis , Humanos , Ligante OX40 , Lactococcus lactis/genética , Imunoterapia , Fatores Imunológicos , Vacinação , Microambiente Tumoral
10.
Rev. esp. enferm. dig ; 114(12): 713-718, diciembre 2022. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-213523

RESUMO

Introducción: la incidencia de cáncer anal ha aumentadoen los últimos años, por lo que el cribado y la detecciónprecoz de la neoplasia intraepitelial anal (AIN) en pacientesde riesgo son una necesidad.Métodos: se realizó un estudio observacional descriptivode pacientes homosexuales (HSH) o mujeres con neoplasiacervical intraepitelial grado III (CIN III), con infección porvirus de la inmunodeficiencia humana (PVIH), incluidos enun programa de cribado de detección de AIN entre marzode 2016 y septiembre de 2019.Resultados: se realizaron 695 citologías anales, 156 conresultados de lesión de bajo grado (LSIL) o lesión de altogrado (HSIL) (22,4 %), y 116 anoscopias de alta resolución(HRA), el 75,3 % de los pacientes con citología alterada. Sehan obtenido 403 biopsias, el 84 % de ellas patológicas; 197biopsias evidenciaron AIN I (49 %) y 96, AIN II y III (24 %); 44eran condilomas (11 %); y el 16 %, mucosa normal.Conclusión: la alta prevalencia de lesiones premalignas y lamejoría del estadiaje de las lesiones tras tratamiento recomienda dicho protocolo. (AU)


Assuntos
Humanos , HIV , Carcinoma in Situ , Comportamento Sexual , Vacinas
11.
Ceska Gynekol ; 87(6): 384-387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36543584

RESUMO

OBJECTIVE: Epidemiology and evaluation of the importance of surgical margins in the treatment of vulvar H-SIL - analysis of own data. MATERIAL AND METHODS: The prospective study included women dia-gnosed with HPV-associated vulvar epithelial neoplasia from 10/2016 to 1/2022. A total of 65 women were included. After surgical treatment, the women were distributed to groups according to surgical margins and were followed-up at regular intervals. RESULTS: Seventeen women (26%) dia-gnosed with HPV-associated vulvar intraepithelial neoplasia were under 49 years, whereas 48 women (74%) were older than 49 years. Recurrence rates of HPV-associated precancers were 12.3%, 1.5% and 3.1% in excisions with positive margins up to 1mm peripheral margins and 1-3mm peripheral margins, respectively. The risk of recurrence when the lesion reaches the margin is statistically significant, compared to a healthy margin of 1-3mm. CONCLUSION: Keeping the minimal healthy margin (1-3mm) seems to be an acceptable risk of recurrence of HPV-associated vulvar intraepithelial neoplasia with positive cosmetic effect and minimal risk of disturbing the psychosexual functions of women. Long-term regular follow-up is necessary.


Assuntos
Carcinoma in Situ , Infecções por Papillomavirus , Neoplasias Vulvares , Feminino , Humanos , Margens de Excisão , Estudos Prospectivos , Vulva/patologia , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia , Carcinoma in Situ/cirurgia , Carcinoma in Situ/patologia , Papillomaviridae
12.
Acta Gastroenterol Belg ; 85(4): 625-631, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36566372

RESUMO

Anal cancer is an uncommon malignancy, comprising only 2.5% of all gastrointestinal malignancies and similar to cervical cancer, the human papillomavirus (HPV) is responsible for the majority of anal cancers. Over the last decades there has been an up to 3-fold increased incidence seen in specific populations at risk such as persons living with HIV (PLWH), men who have sex with men (MSM), woman diagnosed with HPV-related gynaecological precancerous lesions or cancer, solid organ transplant recipients (SOTR) and patients with autoimmune diseases. Although international practice is evolving increasingly towards active screening for and treatment of anal cancer precursors in at-risk groups, currently no organised screening program is in effect in Belgium. Currently, differerent screening options as well as treatment modalities are available. Before commencing a nationwide organised screening program, essential decisions on screening strategies need to be made, based on both scientific as well as financial and logistical facts.


Assuntos
Neoplasias do Ânus , Carcinoma in Situ , Infecções por HIV , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Masculino , Feminino , Humanos , Homossexualidade Masculina , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Bélgica/epidemiologia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/epidemiologia , Canal Anal/patologia
13.
Sci Bull (Beijing) ; 67(8): 813-824, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-36546234

RESUMO

Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors. The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer (GBC), therefore, it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC. This case-control study (n = 85 pairs) found that the high level of plasma soy isoflavone-genistein (GEN) was associated with a lower risk of gallbladder cancer (≥326.00 ng/mL compared to ≤19.30 ng/mL, crude odds ratio 0.15, 95% CI 0.04-0.59; P for trend = 0.016), and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue (n = 85). Consistent with these results, the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo. The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3ß axis, leading to downregulation of the MCM complex in GBC cells. In summary, long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Humanos , Genisteína/farmacologia , Neoplasias da Vesícula Biliar/metabolismo , Estudos de Casos e Controles , Proliferação de Células
14.
Cell Rep ; 41(12): 111837, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36543126

RESUMO

SAG/RBX2 is an E3 ligase, whereas SHOC2 is a RAS-RAF positive regulator. In this study, we address how Sag-Shoc2 crosstalk regulates pancreatic tumorigenesis induced by KrasG12D. Sag deletion increases the size of pancreas and causes the conversion of murine pancreatic intraepithelial neoplasms (mPanINs) to neoplastic cystic lesions with a mechanism involving Shoc2 accumulation, suggesting that Sag determines the pathological process via targeting Shoc2. Shoc2 deletion significantly inhibits pancreas growth, mPanIN formation, and acinar cell transdifferentiation, indicating that Shoc2 is essential for KrasG12D-induced pancreatic tumorigenesis. Likewise, in a primary acinar 3D culture, Sag deletion inhibits acinar-to-ductal transdifferentiation, while Shoc2 deletion significantly reduces the duct-like structures. Mechanistically, SAG is an E3 ligase that targets SHOC2 for degradation to affect both Mapk and mTorc1 pathways. Shoc2 deletion completely rescues the phenotype of neoplastic cystic lesions induced by Sag deletion, indicating physiological relevance of the Sag-Shoc2 crosstalk. Thus, the Sag-Shoc2 axis specifies the pancreatic tumor types induced by KrasG12D.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Camundongos , Animais , Transdução de Sinais , Neoplasias Pancreáticas/patologia , Pâncreas/metabolismo , Carcinoma in Situ/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Carcinogênese , Carcinoma Ductal Pancreático/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transformação Celular Neoplásica/patologia
15.
Am J Dermatopathol ; 44(12): 891-899, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395445

RESUMO

ABSTRACT: Seborrheic keratosis is a common benign neoplasm composed of basaloid keratinocytes. However, little is known about the malignant transformation of the tumor. Eleven cases of seborrheic keratosis with malignant transformation were analyzed. The 11 patients included 5 male patients and 6 female patients with a median age of 75 years at diagnosis (68-90 years). The tumors arose at various sites from the scalp (n = 3) to the lower leg (n = 2). The median tumor size was 12 (10-32) and 40 (20-75) mm in 7 noninvasive and 4 invasive cases, respectively. One patient exhibited in-transit skin metastasis. Histopathology of the malignant components resembled porocarcinoma or inverted follicular keratosis. Bowenoid and pagetoid spreading was frequently observed. The malignant components expressed cytokeratin 5/6 (100%) and GATA3 (73%), but not cytokeratin 7 (0%), cytokeratin 19 (9%), BerEP4 (0%), c-kit (0%), and NUT (0%). No significant immunoreactivity of YAP1 was observed in any of the cases. Mutant-type immunostaining of p53 and PTEN was observed in 91% and 82% of the cases, respectively. An increase in p16 expression was seen in 6 (86%) of the 7 cases with noninvasive carcinoma, although a loss of p16 immunoexpression was seen in the invasive carcinoma component in 3 (75%) of the 4 cases. This study demonstrated that seborrheic keratosis can undergo malignant transformation, particularly in large-sized lesions in elderly patients. Malignant components mimic porocarcinoma or inverted follicular keratosis. Malignant transformation induced by TP53 and PTEN mutations and tumor invasion by CDKN2A inactivating mutations are suggested in this study.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Porocarcinoma Écrino , Ceratose Seborreica , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Humanos , Masculino , Feminino , Idoso , Ceratose Seborreica/patologia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/patologia , Neoplasias das Glândulas Sudoríparas/patologia
16.
Obstet Gynecol ; 140(6): 1061-1075, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36357974

RESUMO

The objectives of this Clinical Expert Series on endometrial hyperplasia are to review the etiology and risk factors, histologic classification and subtypes, malignant progression risks, prevention options, and to outline both surgical and nonsurgical treatment options. Abnormal uterine and postmenopausal bleeding remain the hallmark of endometrial pathology, and up to 10-20% of postmenopausal bleeding will be either hyperplasia or cancer; thus, immediate evaluation of any abnormal bleeding with either tissue procurement for pathology or imaging should be undertaken. Although anyone with a uterus may develop atypical hyperplasia, also known as endometrial intraepithelial neoplasia (EIN), genetic predispositions (eg, Lynch syndrome), obesity, chronic anovulation, and polycystic ovarian syndrome all markedly increase these risks, whereas use of oral contraceptive pills or progesterone-containing intrauterine devices will decrease the risk. An EIN diagnosis carries a high risk of concomitant endometrial cancer or eventual progression to cancer in the absence of treatment. The definitive and curative treatment for EIN remains hysterectomy; however, the obesity epidemic, the potential desire for fertility-sparing treatments, the recognition of varying rates of malignant transformation, medical comorbidities, and an aging population all may factor into decisions to employ nonsurgical treatment modalities.


Assuntos
Carcinoma in Situ , Hiperplasia Endometrial , Neoplasias do Endométrio , Idoso , Feminino , Humanos , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/etiologia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Hiperplasia/complicações , Obesidade/complicações , Obesidade/epidemiologia , Hemorragia Uterina/etiologia
17.
Surg Clin North Am ; 102(6): 947-963, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36335930

RESUMO

Lobular neoplasia (LN) is a term that describes atypical epithelial lesions originating in the terminal duct-lobular unit (TDLU) of the breast, including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS). LN is both a risk factor and nonobligate precursor to invasive breast cancer. A diagnosis of LCIS is associated with a 7-to-10-fold increased risk of breast cancer compared with the general population. When classic LN is diagnosed on a core needle biopsy (CNB), the patient may proceed with either increased screening or excisional biopsy of the lesion. Physicians should counsel patients diagnosed with LN on the risk of developing invasive carcinoma and inform them of the current screening and chemoprevention recommendations to reduce risk.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Carcinoma Lobular , Lesões Pré-Cancerosas , Humanos , Feminino , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/patologia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Mama/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Hiperplasia/patologia
18.
J Immunother Cancer ; 10(11)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36323430

RESUMO

BACKGROUND: The complete response rate of cervical high-grade squamous intraepithelial lesion (cHSIL) patients to imiquimod immunotherapy is approximately 60%. Consequently, many patients are exposed to unnecessary adverse effects of imiquimod. On the other hand, conventional surgical large loop excision therapy is associated with increased risk of premature births in subsequent pregnancies. An in-depth analysis of the cHSIL immune microenvironment was performed in order to identify and develop a predictive biomarker for response to imiquimod, to maximize therapy efficacy and to avoid adverse effects in patients unlikely to respond. METHODS: Biopsies of 35 cHSIL patients, before and 10 weeks on imiquimod treatment, were analyzed by two multispectral seven-color immunofluorescence panels for T cell and myeloid cell composition in relation to treatment response. Based on these results a simplified immunohistochemical detection protocol was developed. Samples were scanned with the Vectra multispectral imaging system and cells were automatically identified using machine learning. RESULTS: The immune microenvironment of complete responders (CR) is characterized by a strong and coordinated infiltration by T helper cells (activated PD1+/type 1 Tbet+), M1-like macrophages (CD68+CD163-) and dendritic cells (CD11c+) prior to imiquimod. The lesions of non-responders (NRs) displayed a high infiltration by CD3+FOXP3+ regulatory T cells. At 10 weeks on imiquimod, a strong influx of intraepithelial and stromal CD4+ T cells was observed in CR but not NR patients. A steep decrease in macrophages occurred both in CR and NR patients, leveling the pre-existing differences in myeloid cell composition between the two groups. Based on the pre-existing immune composition differences, the sum of intraepithelial CD4 T cell, macrophage and dendritic cell counts was used to develop a quantitative simplified one color immunohistochemical biomarker, the CHSIL immune biomarker for imiquimod (CIBI), which can be automatically and unbiasedly quantified and has an excellent predictive capacity (receiver operating characteristic area under the curve 0.95, p<0.0001). CONCLUSION: The capacity of cHSIL patients to respond to imiquimod is associated with a pre-existing coordinated local immune process, fostering an imiquimod-mediated increase in local T cell infiltration. The CIBI immunohistochemical biomarker has strong potential to select cHSIL patients with a high likelihood to experience a complete response to imiquimod immunotherapy.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Lesões Intraepiteliais Escamosas , Humanos , Imiquimode/uso terapêutico , Aminoquinolinas/efeitos adversos , Carcinoma in Situ/induzido quimicamente , Carcinoma in Situ/patologia , Lesões Intraepiteliais Escamosas/tratamento farmacológico , Imunoterapia , Biomarcadores , Fatores Imunológicos , Microambiente Tumoral
20.
Actas urol. esp ; 46(9): 521-530, nov. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-211493

RESUMO

Introducción: La displasia urotelial y el carcinoma in situ (CIS) están relacionados con la recurrencia y la progresión del carcinoma urotelial. Diferenciar el CIS y la displasia de la atipia reactiva suele ser difícil sobre la base de las características histológicas. La integración de los hallazgos histológicos con la inmunohistoquímica se utiliza en la práctica habitual para realizar el diagnóstico del CIS y, para ello, se utilizan los marcadores inmunohistoquímicos CK20, CD44, Ki67 y p53 como complemento al estudio histológico.En este trabajo, nos propusimos evaluar CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en pacientes con CIS, mediante una revisión sistemática y un metaanálisis.Materiales y métodosSe realizó una revisión sistemática con búsqueda en bases de datos electrónicas de estudios en inglés publicados desde enero de 2010 hasta abril de 2021. Se consideraron elegibles los estudios que evaluaban la expresión de CK20, CD44, Ki67 y p53 en el CIS.ResultadosEn total, 15 referencias fueron aptas para la revisión cuantitativa. La tasa global de expresión de CK20, CD44, Ki67 y p53 en el CIS fue del 43%, 31%, 44% y 38%, respectivamente.ConclusionesNuestro estudio apoya el consenso de la Sociedad Internacional de Patología Urológica de 2014 sobre la evaluación histológica como método de referencia para diagnosticar el CIS urotelial, y sugiere que una correlación muy estrecha entre los datos morfológicos, inmunohistoquímicos y clínicos es esencial para proporcionar el mejor manejo de los pacientes con carcinoma vesical. (AU)


Introduction: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology.In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.Materials and methodsA systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.ResultsIn total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.ConclusionsOur study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma. (AU)


Assuntos
Humanos , Carcinoma in Situ/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Receptores de Hialuronatos/sangue , Biomarcadores Tumorais/sangue , Imuno-Histoquímica , Queratinas/sangue , Queratina-20/sangue , Antígeno Ki-67/sangue , Proteína Supressora de Tumor p53/sangue
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