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1.
Mol Biol Rep ; 51(1): 109, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227104

RESUMO

Insulinoma is a neuroendocrine tumor. It arises from the uncontrolled proliferation of pancreatic ß cells. In this study, we created an insulinoma tumor model in nude mice. INS-1 cells were injected in two different ways, subcutaneously (S.C.) or intraperitoneally (I.P.). Body weight, tumor weight, and size were measured. ELISA kits were used analyze to Glucose, insulin, and CA19-9 levels in serum, pancreas, and tumor tissues. KCNN4, KCNK1, GLUT2, IR, HSP70, HSF1, and HSP90 levels were analyzed by western blotting of membrane and/or cytosolic fractions of tumor and pancreas tissue. Tumor formation occurred in nude mice, but it did not occur in Wistar albino rats. The tumor has neuroendocrine cell morphology. Insulin and CA19-9 levels increased in pancreas tissue. In tumor tissue, KCNN4 levels were higher in both membrane and cytosolic fractions, while KCNK1 levels were lower in the membrane fraction of the S.C. group. HSP70 levels were also lower in the S.C. group. In pancreas tissue, KCNK1 levels were lower in the membrane fraction of the S.C. and I.P. groups. GLUT2 levels increased in both groups according to the control group, while IR levels decreased in the S.C. group compared to the control group. However, HSF1 levels increased in the I.P. group, while HSP90 decreased in the S.C. group in pancreatic tissues. The S.C. group is a more suitable insulinoma tumor model. KCNN4, KCNK1, and HSP70 proteins may be important biomarkers in the diagnosis and treatment of insulinoma.


Assuntos
Insulinoma , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Ratos , Animais , Camundongos , Camundongos Nus , Antígeno CA-19-9 , Pâncreas , Insulina , Proteínas de Choque Térmico HSP70 , Proteínas de Choque Térmico HSP90
2.
Int J Gynecol Pathol ; 41(5): 447-458, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856570

RESUMO

Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.


Assuntos
Adenocarcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Feminino , Humanos , Papillomaviridae/genética , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia
3.
Hell J Nucl Med ; 25(2): 148-154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913862

RESUMO

OBJECTIVE: Lymph node metastasis is the most important factor both in the selection of treatment since many alternatives have been created in recent years, and in the evaluation of prognosis in lung cancer. The most unpredictable cause of lymph node false positivity in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is anthracosis. The aim of this study is to compare 18F-FDG PET/CT texture information of anthracotic (ALN) and metastatic (MLN) lymph nodes, after re-evaluation of the cytological samples obtained from anthracotic lymph nodes by EBUS-TBNA. SUBJECTS AND METHODS: Ninety nine patients, 78 of whom had primary lung cancer were included in the study. Two hundred and three lymph nodes from 99 patients sampled by EBUS-TBNA and diagnosed cytologically as ALN or MLN were evaluated retrospectively. All ALN were classified as grades 1, 2 and 3 cytologically. Volume of interest (VOI) of 203 lymph nodes was re-drawn and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were recorded. RESULTS: There was a statistically significant difference in MTV and TLG values in MLN and all ALN grades. However, only grade 1-2 ALNs could be differentiated from MLNs with SUVmax, and no statistically significant difference was found in grade 3 ALN and MLN. Metabolic tumor volume and TLG values over 4.10cm3 and 26.57 showed 60% and 59% sensitivity and 83% and 94 specificity respectively for the identification of MLN. CONCLUSION: The contribution of MTV and TLG values of 18F-FDG PET/CT to the differential diagnosis of ALN is much more valuable than SUVmax values, especially for grade 3 anthracosis. It was thought that cytological reporting of only grade 3 ALN could make a better contribution to the 18F-FDG PET/CT evaluation analysis.


Assuntos
Antracose , Neoplasias Pulmonares , Fluordesoxiglucose F18 , Humanos , Linfonodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos
4.
Turk J Med Sci ; 51(1): 204-213, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33155793

RESUMO

Background/aim: Programmed death ligand-1 (PD-L1) is a predictive marker for immunotherapeutic agents. However, heterogeneous staining of PD-L1 can cause false-negative results. The aim of this study is to evaluate the importance of histological patterns on PD-L1 staining heterogeneity in lung adenocarcinomas (LAC). Materials and methods: PD-L1 immunohistochemistry (IHC) stain was performed to two different tissue cores of 128 LAC cases, and cut-off values are given for grouping the cases according to the percentage of staining (1%-10%, 11%-49%, 50%-100%). Staining rates between cores were compared and analyzed by their histological patterns. Also, the relation of the PD-L1 expression with the clinicopathological characteristics of the cases was analyzed. Results: Overall, PD-L1 expression was observed in 53 of 128 cases (41.4%, 1% cut-off), 23.5% of them were positive at 10% cut-off and 14.1% at 50% cut-off. PD-L1 expression was significantly related to the high grade micropapillary and solid patterns of adenocarcinomas (p:0.01). Staining cut-offs were mostly similar between cores (43/50, 86%) (k:0.843). However, 14% of them were positive only in one core (7 of 50). This false negativity was mostly related to the histological patterns. Conclusion: Our data reveal the heterogeneous staining of PD-L1 expression, also micropapillary and solid patterns show higher rates of PDL expression. Therewithal, these findings also highlight the importance of taking into consideration of histological patterns, when choosing a paraffin block for the PDL1.


Assuntos
Adenocarcinoma de Pulmão , Antígeno B7-H1 , Imuno-Histoquímica/métodos , Neoplasias Pulmonares , Coloração e Rotulagem , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias , Seleção de Pacientes , Coloração e Rotulagem/métodos , Coloração e Rotulagem/estatística & dados numéricos
5.
Am J Clin Pathol ; 161(1): 71-82, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37681660

RESUMO

OBJECTIVES: We present the first study validating the recent Dako ALK assay (clone OTI1A4, in vitro diagnostic) for detecting ALK rearrangements in lung adenocarcinoma. METHODS: Lung adenocarcinoma cases between 2011 and 2023 were retrospectively collected to create a cohort of 203 samples. Cases were stained with Dako ALK OTI1A4 and Ventana ALK D5F3 and reviewed by 3 pathologists independently. Correlation between assays, including their sensitivity and specificity, was evaluated. RESULTS: The cohort (n = 203) consisted of resections, core needle biopsies, and cell blocks. Agreement between Dako ALK OTI1A4 and Ventana ALK D5F3 assays was "almost perfect," with κ = 0.89. The sensitivity and specificity of the Dako ALK OTI1A4 assay were 93.3% and 96%, respectively, in a subgroup of 55 molecularly confirmed cases (n = 30 with and n = 25 without ALK rearrangement). CONCLUSIONS: Immunohistochemistry-based assays provide a valid and reasonably priced alternative, especially in settings where molecular confirmatory tests are neither offered nor accessible. Given high interassay and molecular concordance, we propose that the novel Dako OTI1A4 assay can be reliably used to identify cases with ALK rearrangement.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , Estudos Retrospectivos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Rearranjo Gênico
6.
Turk J Obstet Gynecol ; 20(3): 164-173, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667475

RESUMO

Objective: Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD-L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated. Materials and Methods: Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6). Results: Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive. Conclusion: Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.

7.
Diagn Cytopathol ; 51(4): 239-250, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36519435

RESUMO

BACKGROUND: The term radiologic subsolid lung nodule (SLN) represents a heterogeneous group of non-neoplastic and neoplastic lesions. Intraoperative evaluation (IO) is often required to differentiate and diagnose. The current study aims to investigate the feasibility and reliability of scrape cytology (SC) and radiologic solid size correlation for the IO diagnosis of SLNs. METHODS: Sixty-eight patients with SLN signs were eligible to take part in the study due to intraoperatively prepared SC slides. We managed to complete the blind radiologic solid size measurement and cytologic evaluation retrospectively. Cases were grouped into three categories based on their cytological features: Group-0 (Benign), Group-1 (mild atypical features), and Group-2 (severe atypical features/unequivocally carcinoma). IO diagnoses were given by combining the radiologic solid size and cytological findings. RESULTS: Cytological features of Group-1 were observed in 100%, 93%, 32.5%, and 17% of the AIS, MIA, IA, and benign lesions, respectively. Cytological features of Group-2 were observed in 67.5%, and 7% of the IA and MIA, respectively. By combining cytology with radiologic solid size, 100%, 85%, 71%, and 83% of the AIS, IA, MIA, and benign lesions respectively were diagnosed correctly. Fifteen (15%) percent of the IA cases were underdiagnosed as MIA since their radiological solid sizes were less than 0.5 cm with cytological features of Group-1. Conversely, 29% of the MIA cases were overdiagnosed as IA since their radiological solid sizes were greater than 0.5 cm. CONCLUSION: SLNs should be handled with caution in terms of IO management. SC and radiologic solid size correlation both provide a practical and tissue-protecting approach for the IO evaluation of SLNs, ensuring a high consistency between IO and definitive diagnosis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Humanos , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X , Pulmão/patologia
8.
Indian J Pathol Microbiol ; 66(2): 392-395, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077094

RESUMO

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.


Assuntos
Quinase do Linfoma Anaplásico , Cistadenocarcinoma Seroso , Mesotelioma Maligno , Mesotelioma , Neoplasias Ovarianas , Adolescente , Feminino , Humanos , Proteínas de Ligação a Calmodulina/genética , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Proteínas de Membrana/genética , Mesotelioma/diagnóstico , Mesotelioma/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética
9.
J Cardiothorac Surg ; 18(1): 189, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312199

RESUMO

BACKGROUND: Lung cancer is known as the most common and highly metastatic form of cancer worldwide. Tumour node metastasis (TNM) staging is the gold standard classification system for the decision-making process for appropriate treatment. Particularly N status has the most important prognostic value in the absence of distant metastasis. Traditional diagnostic methods are capable of detecting metastasis; however, they may fail to detect micrometastasis, which plays a role in disease recurrence and patients' long-term survival. Occult micrometastasis can change the tumour's TNM staging and, consequently, the patient's treatment regimen. METHODS: The median number of three lymph node tissues were collected from 30 patients who underwent surgery for non-small cell lung cancer. Lymph node tissues were collected from different lymph node stations according to the location of the patient's tumour. CK19, EpCAM and CEACAM5 gene expressions were analysed in tissues using quantitative real-time polymerase chain reaction to detect micrometastasis in distant lymph nodes. RESULTS: Triple positivity was seen in 26 out of 30 patients which 19 patients were upstaged from N0 to N2. While survival was not significantly affected between upstaged and non-upstaged patients, patients upstaged with multiple-station N2 had a significantly higher recurrence and lower survival compared to single-station N2. CONCLUSION: A combination of CK19, EpCAM and CEACAM5 gene expressions in lymph nodes can be used to identify micrometastasis which postoperatively may be used as a tool to predict patients' recurrence and survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno Carcinoembrionário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Molécula de Adesão da Célula Epitelial/genética , Expressão Gênica , Proteínas Ligadas por GPI , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Linfonodos , Micrometástase de Neoplasia/genética , Prognóstico
10.
ACS Appl Bio Mater ; 6(2): 793-805, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36728815

RESUMO

Extracellular matrix (ECM)-derived hydrogels are in demand for use in lung tissue engineering to mimic the native microenvironment of cells in vitro. Decellularization of native tissues has been pursued for preserving organotypic ECM while eliminating cellular content and reconstitution into scaffolds which allows re-cellularization for modeling homeostasis, regeneration, or diseases. Achieving mechanical stability and understanding the effects of the decellularization process on mechanical parameters of the reconstituted ECM hydrogels present a challenge in the field. Stiffness and viscoelasticity are important characteristics of tissue mechanics that regulate crucial cellular processes and their in vitro representation in engineered models is a current aspiration. The effect of decellularization on viscoelastic properties of resulting ECM hydrogels has not yet been addressed. The aim of this study was to establish bovine lung tissue decellularization for the first time via pursuing four different protocols and characterization of reconstituted decellularized lung ECM hydrogels for biochemical and mechanical properties. Our data reveal that bovine lungs provide a reproducible alternative to human lungs for disease modeling with optimal retention of ECM components upon decellularization. We demonstrate that the decellularization method significantly affects ECM content, stiffness, and viscoelastic properties of resulting hydrogels. Lastly, we examined the impact of these aspects on viability, morphology, and growth of lung cancer cells, healthy bronchial epithelial cells, and patient-derived lung organoids.


Assuntos
Hidrogéis , Pulmão , Humanos , Animais , Bovinos , Hidrogéis/química , Matriz Extracelular/química , Engenharia Tecidual/métodos
11.
Turk J Obstet Gynecol ; 19(1): 81-86, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35343222

RESUMO

Endometrial metastasis from the lung primary remains is rare. Moreover, the literature only contains case reports of endometrial metastasis from the primary lung cancer. An 83-year-old female patient presented with postmenopausal uterine bleeding and anemia. Endometrial thickening was detected using transvaginal ultrasound and endometrial curettage was performed. Histopathology revealed adenocarcinoma infiltration on an endometrial polyp surface. On histologic examination, high-grade serous carcinoma and clear cell carcinoma diagnoses were initially considered. The tumor cells were immunohistochemically negative for Wilms' tumor 1 and wild-type for p53 expression; however, it was positive for Napsin A. Primary lung adenocarcinoma (LUAD) metastasis was also included in the differential diagnosis. Thyroid transcription factor 1 was positive, whereas paired box gene 8 (Pax8) was negative in tumor cells. Primary LUAD metastasis was diagnosed since a lung mass was radiologically confirmed. Furthermore, epidermal growth factor receptor-exon 19 mutation was detected by molecular analysis. In addition to the clinical and morphological features, this case report emphasizes the importance of multiple immunohistochemical panel applications for the correct diagnosis.

12.
Ann Ital Chir ; 112022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35587022

RESUMO

AIM: Angiolipoma is uncommon lesion in the breast and has clinical importance due to the potential of confusion with malignant breast lesions. To date, there is no defined diagnosis and treatment algorithm for breast angiolipomas. We aim to contribute to the literature for the diagnosis and treatment of angiolipomas with this case report and literature review. CASE REPORT: A 29-year-old male patient presented with a newly emerged palpable mass in the right breast. Physical examination revealed a palpable mass in the lower inner quadrant of the right breast without any presence of skin changes, nipple discharge or palpable axillary lymph nodes. The lesion was found to be 3 cm in diameter and showed minimal vascularization on Doppler Ultrasound examination. Surgical excision of the lesion was performed and the lesion was diagnosed as angiolipoma. CONCLUSION: Angiolipomas of the breast in male are rare pathological entities and must always be considered during differential diagnosis, as it can be confused clinically, radiologically and pathologically with other lesions, especially with malignant lesions KEY WORDS: Angiolipoma, Breast, Male breast lesions.


Assuntos
Angiolipoma , Neoplasias da Mama Masculina , Adulto , Angiolipoma/diagnóstico por imagem , Angiolipoma/cirurgia , Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama Masculina/cirurgia , Diagnóstico Diferencial , Humanos , Masculino , Ultrassonografia
13.
J Bronchology Interv Pulmonol ; 29(3): 191-197, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35730779

RESUMO

BACKGROUND: The cost-effectiveness and low rate of inadequate sampling with the use of rapid on-site evaluation (ROSE) along with endobronchial ultrasonography (EBUS) is well established. Our aim in this study was to evaluate the correlation of ROSE during EBUS and final cytologic diagnosis and also to see if ROSE might predict the subtype of lung cancer. PATIENTS AND METHODS: All consecutive subjects who attended our clinic between January 2016 and January 2019 for the evaluation of pathologic mediastinal and/or hilar lymph nodes (LNs)/mass using EBUS were enrolled into our prospective study. ROSE was performed in the same operating room with EBUS. ROSE results during EBUS were recorded. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ROSE compared with the final cytologic diagnosis were evaluated. RESULTS: We enrolled 684 LN/mass lesions belonging to 328 patients into this study. When we compared ROSE results and final cytologic diagnosis, these procedures agreed on 91.6% of the LNs (P<0.001). The sensitivity of ROSE and final cytologic diagnosis for granulomatous inflammation was 72.5%, and for lung cancer, it was 89.2% (P<0.001). The sensitivity of ROSE for the adenocarcinoma subtype of lung cancer was 67.7%, and it was 70% for small cell lung cancer. CONCLUSION: ROSE may help to recognize non-small cell lung cancer during EBUS, especially the adenocarcinoma subtype of lung cancer, which will help ensure having sufficient material for molecular analysis.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estudos Prospectivos , Avaliação Rápida no Local , Estudos Retrospectivos , Ultrassonografia
14.
EMBO Mol Med ; 14(2): e13631, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34898002

RESUMO

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Proteínas Proto-Oncogênicas p21(ras) , Animais , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma Maligno/genética , Mesotelioma Maligno/patologia , Camundongos , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
15.
Turk Patoloji Derg ; 37(1): 7-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32876329

RESUMO

OBJECTIVE: Patients with lung adenocarcinoma who harbor ALK gene rearrangements can demonstrate significant clinical benefit with ALK tyrosine kinase inhibitors. Insulin-like growth factor receptor 1 (IGFR1) is a cellular membrane receptor that is overexpressed in many tumors. It plays an important role in cancer progression and is associated with increased postoperative recurrence and poorer disease-free survival. The aim of this study was to determine the EML4-ALK mutation and IGFR1 expression in lung adenocarcinoma and analyze their prognostic value. MATERIAL AND METHOD: In this study, we analyzed the EML4-ALK mutation using the FISH and IHC techniques in 251 lung adenocarcinoma (203 primary resections, 48 metastasectomies) cases. Correlative analyses were performed between the EML4-ALK mutation, the IGFR1, TTF1, and NapsinA expression, and the clinicopathologic factors in lung adenocarcinomas. RESULTS: The EML4-ALK mutation was observed in 3.8% of the cases and it was associated with the solid pattern, signet ring cell morphology, and larger tumor size. IGFR1 expression was identified in 49% of the cases and most of the ALK-mutated cases were also expressing the IGFR1 protein (66%). IGFR1 expression frequency was increased in metastasectomy specimens. CONCLUSION: A solid signet-ring cell pattern or mucinous cribriform pattern was present at least focally in all ALK-positive tumors, consistently with the literature. In addition, IGFR1 expression levels showed an increase in the EML4-ALK-mutated cases in our series, but the clinical significance of this finding should be supported by larger series and survival analysis. Our findings show that IGFR1 expression may be useful as a poor prognostic marker in patients with lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/química , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Receptor IGF Tipo 1/análise , Translocação Genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Aspártico Endopeptidases/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/análise , Feminino , Fusão Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Fatores de Transcrição/análise
16.
Turk Patoloji Derg ; 37(3): 226-232, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34514574

RESUMO

OBJECTIVE: Soft tissue tumors comprise a small proportion of a pathologist's routine practice. Although morphology and immunohistochemistry are quite helpful for diagnosing these tumors, many require molecular tests. Fluorescence in-situ hybridization has been the most commonly used method for the detection of specific genomic alteration, but next generation sequencing (NGS) could be more informative in many ways. Here we present our targeted NGS experience on soft tissue tumors with a series of 20 cases. MATERIAL AND METHOD: The Laboratory Information System (LIS) was screened for soft tissue tumors that had been sequenced by NGS (between January 2018 - February 2021). 20 consecutive cases were included in the study. All cases were sequenced using a commercial targeted sequencing panel designed for soft tissue tumors. RESULTS: We were able to run a reliable sequencing study for 16 (80%) of the cases but 4 (20%) of them failed in quality tests. We have found pathogenic alterations in 12 (60%) of the cases. The most common alterations were EWSR1 fusions, FLI1 being the most common partner. NGS results drastically changed the initial diagnosis, and thus the treatment modalities, in 3 cases (15%): the case with ETV6-NTRK3 fusion, the case with FUS-TFCP2 fusion, and the case of rhabdomyosarcoma (RMS) that was favored to be of the alveolar subtype and turned out to lack FOXO1 fusions. CONCLUSION: A targeted NGS panel is robust and very informative. It not only allows pathologists to further specify and/or confirm their diagnosis but it could also play an important role in predicting the outcome.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Técnicas de Diagnóstico Molecular/métodos , Sarcoma/diagnóstico , Sarcoma/terapia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/terapia , Proteínas de Ligação a DNA , Humanos , Hibridização in Situ Fluorescente , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Fatores de Transcrição
17.
Nucl Med Commun ; 42(8): 922-927, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795612

RESUMO

PURPOSE: In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy. MATERIALS AND METHODS: Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread. RESULTS: There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)max, SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P < 0.001). CONCLUSIONS: In the preoperative PET study inoperable lung adenocarcinoma cases, MTV/CTV ratio higher than 1 was found to predict STAS positivity. As a result, it was found that it provided significant clinical additional information regarding the need for a surgical approach (lobar resection instead of sublobar) and adjuvant chemotherapy.


Assuntos
Adenocarcinoma de Pulmão , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Prognóstico
18.
Eur J Obstet Gynecol Reprod Biol ; 261: 72-77, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33894621

RESUMO

OBJECTIVE: This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. STUDY DESIGN: Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. RESULTS: Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. CONCLUSION: Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.


Assuntos
Neoplasias da Mama , Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Secções Congeladas , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
19.
J BUON ; 26(3): 819-829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268941

RESUMO

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga Tumoral , Turquia , Adulto Jovem
20.
Turk Patoloji Derg ; 36(3): 205-210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692398

RESUMO

OBJECTIVE: Lung cancer is the leading cause of cancer-related death. PD-L1 blockers have become a first-line option for advanced non-small cell lung cancer (NSCLC) patients. Guidelines require the assessment of PD-L1 expression by immunohistochemistry. Although tissue samples are widely used, cytologic samples could be an alternative. In this study, we compared cytologic samples with tissue samples for PD-L1 evaluation in NSCLC cases. MATERIAL AND METHOD: Koç University Hospital, Department of Pathology Laboratory Information System was scanned for all PD-L1 tests performed on NSCLC cases, either on tissue samples or cell blocks. The type of the biopsy/aspiration procedure, the tumor type, patient demographics, and the percentage of PD-L1 positive tumor cells were recorded. A total of 73 tissue samples and 49 cell blocks were found to be eligible for the study. RESULTS: The PD-L1 positivity score was at least 1% in 44 of 73 samples of the tissue group and 19 of 49 samples of the cell block group. Tissue samples showed significantly higher positivity compared to the cell blocks (p=0.020). Comparing the frequency of cases with ≥50% positivity showed no statistically significant difference. A comparison of PD-L1 positivity rates of only the small biopsies and cell blocks also showed no significant difference. CONCLUSION: Although they harbor a limited number of tumor cells, cell blocks prepared from cytologic samples are good alternatives for PD-L1 testing. However, large resections should be used for PD-L1 evaluation whenever possible since even 1% positivity may affect the treatment decision.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Citodiagnóstico/métodos , Neoplasias Pulmonares/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Biópsia por Agulha , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade
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