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1.
Virchows Arch ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34562173

RESUMO

Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of histone H3 lysine 27 trimethylation (H3K27me3) and menopausal status was closely linked to GLS, we examined the effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis. Data for 962 women diagnosed with primary invasive breast cancer were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival and progression-free survival were estimated using Cox regression models. Statistical interaction was assessed on multiplicative scale. There was a beneficial prognostic effect of GLS expression on overall survival for those with low H3K27me3 level (HR = 0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR = 3.90, 95% CI: 1.29-11.78) among premenopausal women, and the statistical interaction was significant (Pinteraction = 0.003). Similar pattern was further observed for progression-free survival (HR = 0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR = 1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, Pinteraction = 0.024). The statistical interaction did not occur among postmenopausal women. Our study showed that the prognostic effects of GLS on breast cancer correlated to the expression level of H3K27me3 and menopausal status, which would help optimize the medication strategies of GLS inhibitors.

2.
Diagn Pathol ; 16(1): 74, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376196

RESUMO

BACKGROUND: With widespread clinical application of imaging techniques, renal space-occupying lesions have been identified at an increasing frequency. Here, we report two rare cases, Castleman disease (CD) and IgG4-related disease (IgG4-RD), presenting primarily with the symptoms and imaging findings of kidney malignancy. CASE PRESENTATION: In case 1, an occupying lesion located in the right renal pelvis was detected using magnetic resonance imaging in a 32-year-old female who presented with hematuria and lumbago. First misdiagnosed as carcinoma of the renal pelvis, the patient underwent right radical nephroureterectomy. However, postoperative pathological and immunohistochemistry studies finally confirmed the diagnosis of CD. In case 2, a 45-year-old male presented with the chief complaint of anuria. Nephrostomy and renal biopsy indicated lymphoma, following which, antegrade urography and computed tomography urography were performed, which revealed bilateral hydronephrosis and mass lesions around the renal pelvis. Partial resection of the masses and frozen section examination indicated the diagnosis of CD. However, the results of postoperative histopathology and immunohistochemistry combined with serum IgG4 were consistent with IgG4-RD. Both the patients recovered well after drug treatment without recurrence of the diseases. CONCLUSIONS: Inflammatory pseudotumor of CD and IgG4-RD with kidney involvement are primarily diagnosed by postoperative histopathology and can pose a preoperative diagnostic challenge because these lesions can masquerade as kidney malignancy. Therefore, we recommend core biopsy as a nonnegligible procedure to evaluate renal masses and potentially prevent unnecessary surgical treatment.

3.
Front Endocrinol (Lausanne) ; 12: 692553, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248850

RESUMO

Adenomatoid tumor (AT) is an uncommon benign neoplasm of mesothelial origin, usually occurring in the female and male genital tracts. Extragenital localization such as the adrenal gland is extremely rare. Until now, only 39 cases of adrenal AT have been reported in the English literature. Here we report two novel cases of adrenal AT that occurred in male patients aged 30 and 31 years. The tumors were discovered incidentally by computed tomography (CT). Macroscopically, the tumors were unilateral and solid, and the greatest dimension of the tumors was 3.5 and 8.0 cm, respectively. Histologically, the tumors consisted of angiomatoid, cystic, and solid patterns and infiltrated the adrenal cortical or medullary tissue. The tumor cells had low nuclear/cytoplasmic ratio, with no pathological mitosis or nuclear pleomorphism. Thread-like bridging strands and signet-ring-like cells could be seen. Immunohistochemically, the tumor cells were positive for epithelial markers (AE1/AE3, CK7) and mesothelial markers (D2-40, calretinin, and WT-1). The Ki-67 index was approximately 1 and 2%, respectively. The differential diagnosis of adrenal AT includes a variety of benign and malignant tumors. The patients had neither local recurrence nor distant metastasis at 21 and 8 months after removal of the tumor. In the literature review, we comprehensively summarized the clinical, morphological, immunohistochemical, and prognostic features of adrenal AT. Adrenal ATs are morphologically and immunophenotypically identical to those that occur in the genital tracts. Combining the histology with immunohistochemical profiles is very supportive in reaching the diagnosis of this benign tumor, helping to avoid misdiagnosis and overtreatment.

4.
J Cardiothorac Surg ; 16(1): 192, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233697

RESUMO

INTRODUCTION: Chondroblastoma is a rare, benign locally but aggressive bone tumor. It accounts for < 1% of primary bony tumors, and mostly arises from long bones; the rib chondroblastoma is especial rare. Due to its rarity, there are no definitive or standard treatment guidelines. CASE PRESENTATION: A case of a 24-year-old male with a chondroblastoma located on the 6th posterior left rib. Computed tomography (CT) demonstrated a rib tumor that was a well-defined oval lesion of 20 mm × 18 mm, with lytic bone destruction. The imaging first diagnosis was Langerhans cell histiocytosis (LCH), a giant cell tumor, or other type of neoplasm. The whole tumor and a part of partial rib were resected by video-assisted thoracoscopy surgery (VATS). Pathological and immunohistochemical (IHC) examination made a diagnosis of chondroblastoma. Compared with traditional open thoracic surgery, VATS can achieve the same effects and cause less injury to patient. No postoperative adjuvant therapy was given, and had followed up 23 months after surgery, there was no recurrence or metastasis. CONCLUSION: Chondroblastoma has a risk of recurrence and metastasis, surgery plays an important role in the treatment of chondroblastoma, VATS can achieve the same outcome as traditional open thoracic surgery with less pain and lung function. Close follow-up is needed postoperative.


Assuntos
Neoplasias Ósseas/cirurgia , Condroblastoma/cirurgia , Cirurgia Torácica Vídeoassistida , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Condroblastoma/diagnóstico por imagem , Condroblastoma/patologia , Humanos , Masculino , Recidiva Local de Neoplasia , Radiografia Torácica , Costelas , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
Medicine (Baltimore) ; 100(26): e26449, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190169

RESUMO

RATIONALE: Anaplastic lymphoma kinase (ALK) inhibitors have been approved for patients with ALK-rearrangement lung cancer. The effect is superior to the standard first-line therapy of pemetrexed plus platinum-based chemotherapy. However, ALK inhibitors are associated with rare and sometimes fatal adverse events. Organizing pneumonitis (OP) is a rare and serious adverse event usually caused by ceritinib, and it is easily misdiagnosed as infectious pneumonia, metastasis, or cancer progression. PATIENT CONCERNS: A 56-year-old female presented with chest tightness and dyspnea for more than 10 days. She was previously healthy with no significant medical history. Workup including chest computed tomography (CT), pathological examination of a biopsy specimen, and next-generation sequencing was consistent with a diagnosis of IVA ALK-rearrangement lung adenocarcinoma. She was treated with pemetrexed plus platinum-based chemotherapy and crizotinib concurrently, followed by maintenance therapy with crizotinib alone and she had an almost complete response. However, about 26 months after beginning treatment she developed multiple brain metastases. Crizotinib was discontinued and she was begun on ceritinib. After about 3 months the brain metastases had almost complete response. After 5 months of ceritinib, however, multiple patchy lesions appeared in the bilateral upper lungs. DIAGNOSES: Treatment with antibiotics had no effect and blood and sputum cultures are negative. A CT-guided biopsy of the upper lung was performed, and pathological hematoxylin-eosin staining and immunohistochemical studies were consistent with OP. INTERVENTIONS: Ceritinib was discontinued, she was begun on prednisone 0.5 mg/kg orally every day, and regular follow-up is necessary. OUTCOMES: CT of the chest 2 and 4 weeks after beginning prednisone showed the lung lesions to be gradually resolving, and she was continued on prednisone for 2 months and gradually reduced the dose of prednisone every 2 weeks. No related adverse events were occurred in patient. LESSONS: OP must be differentiated from infectious pneumonia, metastasis, or cancer progression. The mechanism of OP is still unknown and needs further research. Biopsy plays a role in making a diagnosis of OP. In our patient, discontinuing ceritinib and treating her with prednisone resulted in a good outcome.


Assuntos
Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Pneumonia em Organização Criptogênica , Neoplasias Pulmonares , Prednisona/administração & dosagem , Pirimidinas , Sulfonas , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/fisiopatologia , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Biópsia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Crizotinibe/uso terapêutico , Pneumonia em Organização Criptogênica/induzido quimicamente , Pneumonia em Organização Criptogênica/patologia , Pneumonia em Organização Criptogênica/terapia , Substituição de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
6.
Breast Cancer Res Treat ; 187(3): 867-875, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33604715

RESUMO

PURPOSE: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. METHODS: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. RESULTS: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). CONCLUSIONS: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.


Assuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/genética , Feminino , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Prognóstico , Receptores de Estrogênio
7.
J Cancer Res Clin Oncol ; 145(4): 1027-1035, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30810839

RESUMO

PURPOSE: Lung cancer prevalence with its high mortality rate is a trending topic globally. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The human gene TTN encoding for TITIN protein is known as major mutation gene in many types of tumor including NSCLC. However, it is still controversial that TTN is a cancer-associated candidate considering tumor heterogeneity and complex genetic structure. In-depth researches on correlation between TTN mutation and NSCLC are still limited and discussable. METHODS: Related somatic mutation profiles and attached clinical data were from The Cancer Genome Atlas (TCGA) lung project. Clinical relevance analysis of TTN mutation was evaluated using univariate analysis and a binary logistic regressive model. Survival analysis and screening of independent prognostic factors in mutation types were conducted by Cox proportional hazards models and Kaplan-Meier methods. RESULTS: Available data covering lung adenocarcinoma (n = 517) and lung squamous cell carcinoma (n = 492) were analyzed. TTN genetic mutations exhibited significant association with lung squamous cell carcinoma. Patients with lung squamous cell carcinoma possessed favorable overall survival benefits from TTN mutant type and both favorable overall survival and disease-free survival benefits from TTN/TP53 double mutation. For patients with lung squamous cell carcinoma, about 85% of subjects with TTN mutation harbored missense variations, which was an independent indicator of good prognosis. CONCLUSIONS: Missense mutation of TTN may act as a beneficial role in lung squamous cell carcinoma, but not in lung adenocarcinoma.


Assuntos
Carcinoma de Células Escamosas/genética , Conectina/genética , Neoplasias Pulmonares/genética , Mutação de Sentido Incorreto , Adenocarcinoma de Pulmão/genética , Idoso , Quinase do Linfoma Anaplásico/genética , Receptores ErbB/genética , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteína Supressora de Tumor p53/genética
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