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1.
Hinyokika Kiyo ; 67(8): 395-398, 2021 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-34472323

RESUMO

A 56-year-old man visited a clinic with the chief complaint of frequent micturition and residual sensation of urine. He was referred to our hospital for close examination. Cystoscopy showed a tumor protruding toward the bladder neck from the prostate with stones and debris on the surface. Magnetic resonance imaging showed an encapsulated tumor of iso-intensity in the prostate in T2-weighed images. Prostate specific antigen was 0.88 mg/dl. Transurethral resection of prostate was performed under the diagnosis of benign prostate hyperplasia. During the operation, a solid tumor with mucus deposit was observed. Intraoperative rapid pathological diagnosis was mucinous adenocarcinoma. A radical cystectomy was performed. Pathologically, mucinous adenocarcinoma was distributed in the bladder neck, the prostate and surrounding tissue, but the prostatic urethra was intact. The surgery was assessed to be curative. Neither neoadjuvant nor adjuvant chemotherapy was performed, since the effectiveness of chemotherapy for mucinous adenocarcinoma arising from urothelial epithelium has not been established.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias da Próstata , Ressecção Transuretral da Próstata , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Bexiga Urinária
2.
J Med Case Rep ; 15(1): 423, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344471

RESUMO

BACKGROUND: Only 14 cases of leiomyoma with ureteral origin have been reported previously. Such primary leiomyomas often present as hydronephrosis, making the diagnosis difficult. Radical nephroureterectomy is often performed because of the possible diagnosis of a malignant tumor. We report the 15th case of primary leiomyoma with a ureteral origin. CASE PRESENTATION: A 51-year-old Japanese man presented with a chief complaint of asymptomatic gross hematuria with a history of hypertension. Enhanced computed tomography showed a tumor at the upper part of the right ureter that appeared to be the cause of hydronephrosis and contracted kidney; no retroperitoneal lymphadenopathy and distal metastasis were observed. A well-defined 20-mm (diameter) defect was identified at the upper of the right ureter on retrograde pyelogram with no bladder cancer on cystoscopy. Urine cytology and right divided renal urine cytology findings were negative. Laparoscopic nephroureterectomy was performed, and the extracted tumor measured 20 × 13 mm. Histopathological examination revealed primary leiomyoma with no recurrence 16 months after the operation. CONCLUSIONS: Preoperative examination with the latest available ureteroscopic technology can help preserve renal function in the case of benign tumors by enabling preoperative ureteroscopic biopsy or intraoperative rapid resection. Moreover, nephroureterectomy is recommended in the case of preoperative suspicion of ureteral malignant tumors.


Assuntos
Leiomioma , Ureter , Neoplasias Ureterais , Humanos , Leiomioma/diagnóstico , Leiomioma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nefroureterectomia , Ureter/diagnóstico por imagem , Ureter/cirurgia , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias Ureterais/cirurgia
4.
Eur Urol Focus ; 7(4): 687-691, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34393083

RESUMO

Diagnosis and Gleason grading of prostate cancer in biopsies are critical for the clinical management of men with prostate cancer. Despite this, the high grading variability among pathologists leads to the potential for under- and overtreatment. Artificial intelligence (AI) systems have shown promise in assisting pathologists to perform Gleason grading, which could help address this problem. In this mini-review, we highlight studies reporting on the development of AI systems for cancer detection and Gleason grading, and discuss the progress needed for widespread clinical implementation, as well as anticipated future developments. PATIENT SUMMARY: This mini-review summarizes the evidence relating to the validation of artificial intelligence (AI)-assisted cancer detection and Gleason grading of prostate cancer in biopsies, and highlights the remaining steps required prior to its widespread clinical implementation. We found that, although there is strong evidence to show that AI is able to perform Gleason grading on par with experienced uropathologists, more work is needed to ensure the accuracy of results from AI systems in diverse settings across different patient populations, digitization platforms, and pathology laboratories.

6.
Int J Clin Oncol ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34291367

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010-2015. METHODS: This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan-Meier methodology. RESULTS: PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1-positive patients was 30.9 months (95% CI 25.5-35.7) versus 37.5 months (95% CI 34.0-42.6) for PD-L1-negative patients (HR 1.04 [90% CI 0.89-1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1-positive and -negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986). CONCLUSIONS: This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34275008

RESUMO

BACKGROUND: B7 homolog 4 (B7-H4) is a negative regulator of immune responses, but its immunoregulatory role in the tumor microenvironment of upper urinary tract urothelial carcinoma (UTUC) remains unclear. METHODS: We measured the immunohistochemical expression of B7-H4, CD8 and T cell intracellular antigen 1 (TIA-1), a marker of activated CD8, in 133 patients with UTUC who underwent nephroureterectomy. We also studied the relationship between B7-H4, CD8 and TIA-1 expression and clinicopathological characteristics. RESULTS: B7-H4 was mainly expressed on the surface in tumor cells, while CD8 and TIA-1 were often expressed in tumor-infiltrating lymphocytes. Elevated expression of B7-H4 in tumor cells was associated with a poorer histological grade, higher pT stage, regional lymph node metastasis, lymphovascular invasion, poorer response of recurrent metastatic lesions to systemic chemotherapy and shorter overall survival. Expression of CD-8 or TIA-1 alone did not correlate directly with clinicopathological characteristics, but among the patients with higher B7-H4 expression in the primary tumors, those with higher CD8 or TIA-1 expression had a better response to systemic chemotherapy, and longer survival, than these with lower CD8 or TIA-1 expression. Cox multivariate regression analysis revealed that higher expression of B7-H4 was associated with shorter overall survival. CONCLUSIONS: These findings suggest that B7-H4 expression in the tumor microenvironment influences the progression of UTUC through cancer immunity and metabolic activity. Tumor cell-associated B7-H4 might be a potential target for cancer immunotherapies.

8.
Cancer Sci ; 112(10): 4037-4049, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309966

RESUMO

Immunotherapy with immune-checkpoint therapy has recently been used to treat oral squamous cell carcinomas (OSCCs). However, improvements in current immunotherapy are expected because response rates are limited. Transforming growth factor-ß (TGF-ß) creates an immunosuppressive tumor microenvironment (TME) by inducing the production of regulatory T-cells (Tregs) and cancer-associated fibroblasts and inhibiting the function of cytotoxic T-lymphocytes (CTLs) and natural killer cells. TGF-ß may be an important target in the development of novel cancer immunotherapies. In this study, we investigated the suppressive effect of TGF-ß on CTL function in vitro using OSCC cell lines and their specific CTLs. Moreover, TGFB1 mRNA expression and T-cell infiltration in 25 OSCC tissues were examined by in situ hybridization and multifluorescence immunohistochemistry. We found that TGF-ß suppressed the function of antigen-specific CTLs in the priming and effector phases in vitro. Additionally, TGF-ß inhibitor effectively restored the CTL function, and TGFB1 mRNA was primarily expressed in the tumor invasive front. Interestingly, we found a significant negative correlation between TGFB1 mRNA expression and the CD8+ T-cell/Treg ratio and between TGFB1 mRNA expression and the Ki-67 expression in CD8+ T-cells, indicating that TGF-ß also suppressed the function of CTLs in situ. Our findings suggest that the regulation of TGF-ß function restores the immunosuppressive TME to active status and is important for developing new immunotherapeutic strategies, such as a combination of immune-checkpoint inhibitors and TGF-ß inhibitors, for OSCCs.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia Adotiva/métodos , Neoplasias Bucais/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Linfócitos T Citotóxicos/efeitos dos fármacos , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Fibroblastos Associados a Câncer/citologia , Fibroblastos Associados a Câncer/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Interferon gama/análise , Interferon gama/metabolismo , Antígeno Ki-67/metabolismo , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , RNA Mensageiro/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Sais de Tetrazólio/farmacologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
10.
Surg Case Rep ; 7(1): 145, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34138407

RESUMO

BACKGROUND: Advanced hepatocellular carcinoma (HCC) can often spread as intrahepatic metastases. Extrahepatic metastasis (e.g., lung, lymph nodes, and bones) is rare, and gallbladder metastasis from HCC is extremely rare. CASE PRESENTATION: A 66-year-old woman who presented with right hypochondrial pain was referred to our hospital for further examination of a liver tumor. The blood chemistry data showed elevated levels of serum α-fetoprotein (AFP) (3730 ng/mL), protein induced by vitamin K absence or antagonist II (PIVKA-II) (130 mAU/mL), and carcinoembryonic antigen (CEA) (358.6 ng/mL). Hepatitis B surface antigen and hepatitis C virus antibody were negative. Dynamic computed tomography (CT) showed a tumor measuring 12 × 7 cm in the right lobe of the liver. This tumor was contrast-enhanced in the hepatic arterial phase and then became less dense than the liver parenchyma in the portal phase. A well-enhanced tumor was found in the gallbladder. No regional lymph nodes were enlarged. Contrast-enhanced magnetic resonance imaging (MRI) demonstrated that the liver tumor showed a pattern of early enhancement and washout. The gallbladder tumor was also detected as an enhanced mass. Endoscopic retrograde cholangiography (ERC) showed compression of the left hepatic duct due to the liver tumor. The patient was diagnosed with simultaneous HCC and gallbladder cancer. Right hepatic trisectionectomy and caudate lobectomy with extrahepatic bile duct resection were performed. Histopathological examination of the resected liver specimen showed a poorly differentiated HCC cell component with a trabecular and solid growth, and diffuse invasion of the portal vein. The same tumor cells were found in the gallbladder, but no continuity with the liver tumor was identified. Immunohistochemistry of the liver tumor and gallbladder was positive for AFP, Glypican 3, and CK7, and negative for CK19. The final pathological diagnosis was the gallbladder metastasis from HCC. A follow-up diagnostic image 33 months after surgery showed a mass in the upper lobe of the left lung. The patient underwent left upper lobectomy. Postoperative pathology revealed that the lung lesion was a metastasis of HCC. The patient was still alive with lung metastasis and was being treated with a molecular-targeting drug in good health 42 months after the initial surgery. CONCLUSIONS: The standard treatment for advanced HCC with extrahepatic metastases is molecularly targeted drugs, but surgery is also an option if the lesion can be resected en bloc without remnants.

11.
Fam Cancer ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34156580

RESUMO

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40-44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

12.
Pathology ; 53(5): 574-578, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34154844

RESUMO

Corpora amylacea (CA) is usually present in benign prostatic ducts and acini, and its presence is considered suggestive of negative or low-risk prostate cancer. The clinicopathological definition of CA among prostate cancer cells (CAPCCs)-described as CA entirely surrounded by invasive cancer cells-has not been discussed. As intraductal carcinoma of the prostate (IDC-P) is a well-known adverse prognostic factor in prostate cancer, this study aimed to elucidate the relationship between CAPCC and IDC-P. We enrolled 366 patients who underwent robotic-assisted radical prostatectomies between 2012 and 2018 at Aichi Medical University Hospital. All surgical specimens were independently reviewed by two genitourinary pathologists. The median age of the patients was 68.5 years; the median serum prostate-specific antigen was 6.49 ng/mL. IDC-P was observed in 143 (39.1%) patients, while the presence of CAPCC was observed in 47 cases (12.8%). Patients with CAPCC were associated with more advanced clinical and pathological T stages, as well as Gleason scores, than those without CAPCC (p=0.018, p<0.001, p=0.036). Notably, the presence of CAPCC was significantly associated with the presence of IDC-P (39 cases) and a high Gleason score compared with the absence of CAPCC (12 cases) (p<0.001 and p=0.036, respectively). The presence of CAPCC is an adverse pathological feature, often closely related to IDC-P. Therefore, CAPCC may be a surrogate finding to detect IDC-P via haematoxylin and eosin staining.

13.
Thorac Cancer ; 12(14): 2134-2137, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34096185

RESUMO

Endobronchial resection using a bronchoscope is often selected as treatment for carcinoid tumors located in the central airways. However, massive bleeding is one of the most serious complications during bronchoscopic surgery. Here, we report the case of a 77-year-old female with a typical carcinoid tumor located in the right truncus intermedius who underwent bronchial artery embolization (BAE) one day before endobronchial intervention using a flexible bronchoscope. The tumor was successfully resected without bleeding. BAE prior to endobronchial resection of carcinoid tumors may be useful for reducing the risk of bleeding.

14.
BJU Int ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110696

RESUMO

OBJECTIVES: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo-resistant urothelial carcinoma (UC). PATIENTS AND METHODS: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68-1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15-0.90; P = 0.023) compared to patients with PUC. CONCLUSIONS: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo-resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.

15.
Pathology ; 53(6): 720-727, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33947521

RESUMO

Acquired cystic disease (ACD) associated renal cell carcinoma (RCC) is designated as a new subtype unique to patients with end-stage renal disease (ESRD) according to the 2016 World Health Organization (WHO) classification. However, the oncological outcomes of the prognostic factors for patients with this subtype are not fully understood. In the present study, we compared the survival of ACD associated RCC patients who underwent nephrectomy with that of patients with other histological subtypes who developed ESRD. Over 378 patients who underwent nephrectomy at three Japanese institutes between 1987 and 2016 were included in this study. A central pathologist reviewed the sections from all patients according to the 2016 WHO classification. The central pathological review showed a clear cell subtype in 165 patients (43.6%), ACD associated RCC in 112 (29.6%), papillary in 61 (16.1%), and others in 40 (10.7%). The proportion of patients with pathological stage 1 was extremely high in both clear cell and ACD associated RCC cohorts (86.6%, 85.7%). The cancer specific survival (CSS) and recurrence free survival rates of patients with ACD associated RCC were comparable with those with clear cell carcinoma and significantly better than those with the papillary subtype. The factors predictive of unfavourable outcomes were long dialysis duration, tumour size, pathological stage, grade 4 tumour, and the presence of lymphovascular invasion or a sarcomatoid component. Patients with a pre-operative dialysis duration of 20 years or longer showed a significantly worse CSS than other patients, probably owing to sarcomatoid differentiation and stage migration during the advanced stages. In conclusion, this study included the largest number of patients with ACD associated RCC, showing a survival similar to that of clear cell histology patients with ESRD, except for the rarity of late recurrence. ACD associated RCC was not as indolent as initially recognised when patients were on long term dialysis.

16.
Int J Mol Sci ; 22(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33799989

RESUMO

Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47-SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47-SIRPA pathway-modulating therapies may be effective in patients with CRC.


Assuntos
Antígenos de Diferenciação/metabolismo , Antígeno CD47/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Receptores Imunológicos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Superfície Celular/metabolismo , Análise de Sobrevida
17.
Int J Surg Pathol ; : 10668969211008980, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847540

RESUMO

A 40-year-old, male, Japanese patient presented with the complaint of painless, right testicular swelling. Tumor markers for testicular cancer were normal. He underwent radical orchiectomy with the clinical diagnosis of stage I seminoma. Pathological examination revealed seminoma and coexisting neuroendocrine tumor (NET). Germ cell neoplasia in situ (GCNIS) was present in the vicinity of seminoma, but there was no continuity between NET and seminoma. Tumor cells of both lesions displayed amplification of 12p and isochromosome 12p on fluorescence in situ hybridization, suggesting that both tumors originated from GCNIS. The present report is the first to describe a case of primary testicular NET coexisting with seminoma in an ipsilateral testis.

18.
Am J Surg Pathol ; 45(6): 832-840, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33899787

RESUMO

On the basis of immunohistochemistry, diffuse large B-cell lymphoma (DLBCL) is categorized as a germinal center B-cell (GCB) or non-GCB subtype. Recent integrated genomic analyses have highlighted the importance of the JAK-STAT3 pathway in the molecular pathogenesis of DLBCL. However, its relevance to clinical outcomes remains controversial. Therefore, we evaluated the extent of the nuclear expression of phosphorylated STAT3 (pSTAT3), a surrogate marker of signal transducer and activator of transcription 3 (STAT3) activation, by immunohistochemistry. We also analyzed the potential relationship between pSTAT3 positivity (defined as ≥40% positive neoplastic cells) and clinicopathologic characteristics in 294 patients with DLBCL. pSTAT3 was detected in 122 patients (42%), with a higher rate in the non-GCB subtype than in the GCB subtype (57% vs. 28%, P<0.001). Factors potentially activating STAT3, MYD88L265P, and Epstein-Barr virus-encoded small RNA were identified in the pSTAT3-positive non-GCB subtype, whereas the pSTAT3-positive GCB subtype often showed STAT3 mutations and lacked EZH2 mutations and the rearrangements of BCL2 and MYC. Multivariate analyses revealed that the pSTAT3-positive GCB subtype showed a favorable prognosis (HR: 0.17; 95% confidence interval, 0.04-0.7; P=0.014). These findings suggest that pSTAT3 positivity may have a unique impact on the clinicopathologic characteristics of DLBCL, making it a promising novel marker for the favorable prognosis of patients with the GCB subtype.


Assuntos
Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/química , Fator de Transcrição STAT3/análise , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Rearranjo Gênico , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Japão , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Fator 88 de Diferenciação Mieloide/genética , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Viral/genética , Fator de Transcrição STAT3/genética , Proteína 1 Supressora da Sinalização de Citocina/genética
19.
Ann Diagn Pathol ; 52: 151733, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33780691

RESUMO

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.

20.
Biomed Res Int ; 2021: 6644897, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33778077

RESUMO

Objective: Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase-2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed MMP2 mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University's Otolaryngology Department, were analyzed for MMP2 expression level, using RNA-in situ hybridization. Results: There were no significant differences in MMP2 mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type (p < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida (p < 0.001). MMP2 mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium. Conclusion: Our study reveals that MMP2 mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of MMP2 mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.


Assuntos
Colesteatoma/congênito , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Metaloproteinase 2 da Matriz/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Adolescente , Criança , Pré-Escolar , Colesteatoma/classificação , Colesteatoma/enzimologia , Colesteatoma/patologia , Feminino , Humanos , Masculino
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