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INTRODUCTION: We investigated whether the infiltration of tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), as evaluated by hematoxylin and eosin (H&E) staining, could be a prognostic marker. We also explored on the relationship between TILs and mechanistic target of rapamycin (mTOR) and how it regulates immune effector responses in GC. METHODS: A total of 183 patients with available data on TIL were included. TIL infiltration was evaluated using H&E staining. We also conducted immunohistochemistry to determine mTOR expression. RESULTS: Positive TIL infiltration was defined as TILs ≥20%. There were 72 (39.3%) and 111 (60.7%) positive and negative cases, respectively. TILs positivity significantly correlated with both absence of lymph node metastasis (p = 0.037) and negative p-mTOR expression (p = 0.040). TIL infiltration correlated with a significantly better overall (p = 0.046) and disease-free (p = 0.020) survival. CONCLUSION: mTOR possibly suppresses TIL infiltration in GC. H&E staining is an effective tool for evaluating the immune status of GC patients. H&E staining may be used in clinical practice to monitor treatment response in GC.
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Linfócitos do Interstício Tumoral , Neoplasias Gástricas , Humanos , Prognóstico , Linfócitos do Interstício Tumoral/patologia , Metástase Linfática/patologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-ß signaling), wnt3a, and E-cadherin (epithelial-mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p < 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with increased wnt3a signaling (p = 0.0028) and decreased E-cadherin expression (p = 0.0055); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). In contrast, high TGFBI expression in the presence of LPS was associated with a worse prognosis than that in the absence of LPS (p = 0.049). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had disease control rates of 66.7% and 11.8%, respectively (p = 0.088). Lipopolysaccharide positivity was associated with wnt3a, TGF-ß signaling, and epithelial-mesenchymal transition and was considered to tend to promote therapeutic resistance to nivolumab.
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Lipopolissacarídeos , Neoplasias Gástricas , Humanos , Nivolumabe/uso terapêutico , Antígeno B7-H1/genética , Neoplasias Gástricas/tratamento farmacológico , Estudos Retrospectivos , Biomarcadores , Caderinas/metabolismo , Fator de Crescimento Transformador beta , Transição Epitelial-Mesenquimal/genéticaRESUMO
INTRODUCTION: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/ß-catenin activity in GC. METHODS: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and ß-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features. RESULTS: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013). CONCLUSION: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , beta Catenina , Estudos Retrospectivos , Prognóstico , Biomarcadores Tumorais/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
INTRODUCTION: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. METHODS: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. RESULTS: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). CONCLUSION: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.
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Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Tegafur/uso terapêutico , Idoso , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Proteína-1 Reguladora de Fusão/metabolismo , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Fosforilação , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Serina-Treonina Quinases TOR/metabolismoRESUMO
We report a case of primary central nervous system lymphoma (PCNSL) in an 81-year-old man who had undergone radical cystectomy with an ileal conduit urostomy due to a diagnosis of muscle-invasive bladder cancer. The postoperative diagnosis was invasive urothelial carcinoma (pT2bN1M0, stage IV). Gemcitabine-cisplatin therapy was provided as adjuvant chemotherapy, and there was no recurrence during follow-up. Four years after surgery, he visited the emergency department because of weakness of the lower extremities and stuttering. He was found to have a parietal lobe mass on magnetic resonance imaging (MRI) and hospitalized with suspicion of brain metastasis. Despite examination by a neurosurgeon, it was not possible to make a clinical diagnosis, and the patient gradually deteriorated and died 21 days later. The pathology results were diagnostic of PCNSL.
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Carcinoma de Células de Transição , Linfoma , Neoplasias da Bexiga Urinária , Idoso de 80 Anos ou mais , Sistema Nervoso Central , Cistectomia , Humanos , Masculino , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
A 51-year-old man presented with a 2-week history of malaise. MRI revealed a large solid and cystic lesion with ring enhancement measuring 6.5 cm in diameter in the right frontal lobe. Histologically, the tumor consisted of various components: diffuse growth of atypical astrocytic cells consistent with glioblastoma, fascicular proliferation of atypical spindle cells such as fibrosarcoma, clusters of primitive neuronal cells, and foci of ependymal cells. The sarcomatous component also focally exhibited chondroid and osteoid differentiation. Immunohistochemically, tumor cells in the primitive neuronal component were immunoreactive for synaptophysin and CD56. The spindle cells were immunopositive for Slug and Twist, regulators of epithelial-mesenchymal transition. Direct DNA sequencing demonstrated C228T mutation in the TERT promoter in astrocytic, sarcomatous and primitive neuronal components, suggesting their identical origin. Although a few cases of gliosarcoma with primitive neuronal differentiation have previously been described, the finding that neuronal, glial and sarcomatous components share an identical mutation of the TERT promoter has not been reported. The tumor recurred at the original site 11 months after the first surgery. Interestingly, the recurrent tumor was composed exclusively of a glioblastomatous component, unlike past cases of recurrent gliosarcoma.
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A laparoscopy-assisted right hemicolectomy and D3 lymph node dissection were performed to treat a 60-year-old woman with ascending colon cancer. Microscopically, the resected specimen was diagnosed as adenocarcinoma(tub1>tub2, pSS, pN1, M0). Adjuvant chemotherapy using UFT/UZEL was administered for 6 months. Enlarged para-aortic lymph nodes were identified by follow-up CT 2 years post operation, and a para-aortic lymph node dissection was performed. Microscopic examination revealed that the #216 b1 int lymph node contained poorly differentiated metastatic adenocarcinoma. After 36 courses of FOLFOX as adjuvant chemotherapy, the chemotherapy was discontinued because of an adverse event. She has remained well without recurrence for 5 years after the second surgery. There have been reports of survival improvements by surgical resections in patients with solitary para-aorta lymph node metastases of colorectal cancer. These observations suggest that the surgical therapy may have contributed to the improved prognosis in the present case.
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Quimioterapia Adjuvante , Colo Ascendente , Neoplasias do Colo/tratamento farmacológico , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines. RESULTS: Multivariate and Kaplan-Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis. CONCLUSIONS: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.
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Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Estatmina/genética , Neoplasias Gástricas/tratamento farmacológico , Idoso , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Dentatorubral-pallidoluysian atrophy (DRPLA), one of the polyglutamine diseases, has not been reported in combination with ganglioglioma (GG). Herein, we report an autopsy case of a 72-year-old man with DRPLA with a small GG component harboring neurofibrillary tangles (NFTs) and polyglutamine aggregates. NFTs, cytoplasmic accumulations of hyper-phosphorylated tau, are mainly observed in Alzheimer's disease (AD) and other tau-associated neurodegenerative disorders. NFTs can also be present in normal aging, and are occasionally observed in low-grade central nervous system (CNS) neoplasms such as GG. In the present case, whole brain examination demonstrated widespread deposition of polyglutamine aggregates, including GG, whereas NFTs were restricted to the GG component. In addition, no other AD or aging-related neuropathological structures were detected throughout the CNS. These findings may provide us with clues to elucidate the pathogenetic mechanisms that neuronal neoplasms may have to develop NFTs regardless of aging, and that polyglutamine may accumulate in neoplastic neurons in polyglutamine disease.
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Neoplasias Encefálicas/patologia , Ganglioglioma/patologia , Epilepsias Mioclônicas Progressivas/patologia , Emaranhados Neurofibrilares/patologia , Idoso , Neoplasias Encefálicas/complicações , Ganglioglioma/complicações , Humanos , Masculino , Epilepsias Mioclônicas Progressivas/complicações , PeptídeosRESUMO
BACKGROUND: Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. METHODS: We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. RESULTS: PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. CONCLUSION: Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.
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Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Carcinoma de Células em Anel de Sinete/secundário , Fluoruracila/uso terapêutico , Proteína Forkhead Box O1/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose , Western Blotting , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Carcinoma de Células em Anel de Sinete/metabolismo , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/genética , RNA Interferente Pequeno/genética , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND: Transcription factor prospero homeobox 1 (PROX1) has been identified as a master regulator of lymphangiogenesis associated with metastasis. Although PROX1 expression has been investigated in several cancers, its clinical significance remains controversial and needs further validation. In this study, we investigated the clinical and functional significance of PROX1 and PROX1 regulator hypoxia-inducible factor 1α (HIF1α) in esophageal squamous cell carcinoma (ESCC). METHODS: A total of 117 samples from ESCC patients were analyzed for PROX1, HIF1α, and E-cadherin expression by immunohistochemistry; correlation with clinicopathological characteristics was determined. PROX1 function was evaluated in PROX1 small interfering RNA (siRNA)-transfected human ESCC cells in vitro by assessing cell proliferation and migration. RESULTS: PROX1 expression was higher in ESCC than in normal tissues. Patients with higher PROX1 expression (n = 26) had increased nuclear accumulation of HIF1α (p = 0.004) and more advanced metastasis, both lymph node (N factor; p = 0.09) and hematogenous (M factor; p = 0.04), than those with lower PROX1 expression (n = 91). In addition, high PROX1 and HIF1α expression correlated with low levels of E-cadherin, an epithelial cell marker. Analysis of overall and cancer-specific survival indicated that elevated PROX1 expression was significantly correlated with poor prognosis (p = 0.0064). PROX1 downregulation in ESCC cells inhibited cellular proliferation and migration (p < 0.05). Hypoxia restored PROX1 levels that were reduced by PROX1-specific siRNA. CONCLUSION: Our data suggest that high expression of PROX1 in ESCC could be used as an indicator of poor prognosis, and that PROX1 is a promising candidate molecular target for ESCC treatment.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Núcleo Celular/metabolismo , Neoplasias Esofágicas/patologia , Proteínas de Homeodomínio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/genética , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Interferente Pequeno/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genéticaRESUMO
The present study examined the surgical outcome and prognosis of patients with poorly cohesive carcinoma (PCC), and characterized the molecular pathological factors, epithelial-mesenchymal transition (EMT) and interstitial signals of the disease. A total of 281 patients who underwent gastric cancer (GC) surgery between April 2015 and August 2020 were included. Furthermore, tissue samples from another 197 patients with GC who underwent surgery between 1999 and 2003 were assessed using a tissue microarray. Preoperatively treated cases and endoscopic submucosal dissection cases were excluded, and multiple blocks containing the invasion region were collected for tissue microarray. For tissue microarray analysis, the clinicopathological factors of protein wnt3a (wnt3a), leucine-rich repeat-containing G-protein coupled receptor 5, transforming growth factor-ß-induced, phosphorylated serine/threonine-protein kinase mTOR and E-cadherin expression were collected as EMT markers. The results of the surgical case evaluation and tissue microarray indicated that PCC was more common in younger patients and women, as the ratio of women to men was higher in the PCC group compared with that in the non-PCC group. However, none of the results revealed that the prognosis was worse in all patients with PCC compared with the non-PCC group. Furthermore, in the tissue microarray study, PCC samples exhibited significantly decreased expression of the cell adhesion molecule E-cadherin, suggesting enhanced EMT, which activates wnt3a signaling. PCC with increased EMT was significantly associated with a poor prognosis.
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BACKGROUND: The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor cell growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine biological significance of LAT1 expression and investigate whether LAT1 could be a prognostic biomarker for biliary tract cancer. METHODS: A total of 139 consecutive patients with resected pathologic stage I-IV biliary tract adenocarcinoma were retrospectively reviewed. Tumor specimens were stained by immunohistochemistry for LAT1, Ki-67, microvessel density determined by CD34, and p53; and prognosis of patients was correlated. Biological significance of LAT1 expression was investigated by in vitro and in vivo experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using cholangiocarcinoma cell line. RESULTS: In total patients, high LAT1 expressions were recognized in 64.0%. The expression of LAT1 was closely correlated with lymphatic metastases, cell proliferation and angiogenesis, and was a significant indicator for predicting poor outcome after surgery. LAT1 expression was a significant independent predictor by multivariate analysis. Both in vitro and in vivo preliminary experiments indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to gemcitabine and 5-FU. CONCLUSIONS: High expression of LAT1 is a promising pathological marker to predict the outcome in patients with biliary tract adenocarcinoma. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.
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Adenocarcinoma/metabolismo , Neoplasias do Sistema Biliar/metabolismo , Biomarcadores Tumorais/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antimetabólitos Antineoplásicos/farmacologia , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Linhagem Celular Tumoral , Proliferação de Células , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Intervalo Livre de Doença , Feminino , Fluoruracila/farmacologia , Proteína-1 Reguladora de Fusão/metabolismo , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto , GencitabinaRESUMO
PURPOSE: One of the typical modifications on the surface of cancer cells is sialylation of terminal carbohydrates. The expression of several types of sialylation of glycoconjugates was investigated in colorectal cancer. METHODS: The cancer tissue specimens obtained from 65 colorectal cancer patients were stained with sialic acid-binding lectins from Maackia amurensis (MAM), Sambucus sieboldiana (SSA), Maackia amurensis agglutinin (MAA) and monoclonal antibodies, and compared with their clinicopathological features. RESULTS: Cancer tissue specimens from 44.6% of patients had positive staining with MAM, which recognized α2,3sialylated type 2 chain (NeuAcα2,3Galß1,4GlcNAcßR) structures, but normal colorectal mucosa showed only weak staining with MAM was observed. More lymph node metastases and lymphatic invasion were seen in patients with positive staining with MAM (P < 0.01), while not with other lectins or antibodies that recognized sialylated glycoconjugates or sialyl Lewis-related antigens. The five-year survival rate of patients with MAM-positive staining was significantly lower than that with MAM-negative staining when including T0-1 cases, but there was no difference in cases with T2-4. There was no difference in the patients' survival rates when the tissues were stained with MAA, SSA or PNA lectins. CONCLUSION: α2,3Sialylated type 2 chain structures were predominantly expressed in colorectal tissues associated with the malignant transformation, in particular, with lymphatic spread of distal colorectal adenocarcinomas.
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Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Glicoconjugados/metabolismo , Ácidos Siálicos/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/química , Transformação Celular Neoplásica/química , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Colectomia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Glicoconjugados/química , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Lectinas de Plantas , Reto/cirurgia , Ácidos Siálicos/química , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Kikuchi-Fujimoto disease (KFD) is a rare and self-limiting disorder that predominantly affects young individuals of Asian descent. This case report describes familial KFD in partially human leukocyte antigen (HLA)-matched siblings. An adolescent male presented with cervical lymphadenopathy and elevated lactate dehydrogenase (LDH) levels, diagnosed by biopsy as KFD; approximately one year later, his sister presented with similar symptoms. Both siblings were found to carry the HLA-DPB1*0202 allele, which is commonly associated with KFD. These cases highlight a genetic component in KFD and encourage further genetic research to delineate the pathogenesis of the disease.
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The metastasis of breast cancer to the gastrointestinal tract is rare. Herein, we presented the case of an 85-year-old woman who had a history of invasive lobular carcinoma and experienced complete colon rupture due to relatively low-energy trauma. The patient underwent bilateral total mastectomy and axillary dissection following preoperative chemotherapy 6 years ago. She had a local recurrence 2 years after the surgery and underwent chemotherapy. Subsequently, the cancer metastasized to the thoracolumbar area and retroperitoneum. In addition, the patient fell from a height of 30 cm while hanging laundry and her abdomen hit a hose reel. Emergency surgery was performed, and the entire circumference of the sigmoid colon was ruptured. The ruptured colon lesion was resected, and the stump was closed. A double-barrel transverse colostomy was created as it was impossible to lift the stump up to the abdominal wall. Histopathological examination revealed the invasive lobular carcinoma metastasis and a linitis plastica-like change of the colon wall, which probably consequently weakened. In addition, minimal trauma can damage the gastrointestinal tract that had invasive lobular carcinoma metastasis.
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Neoplasias da Mama , Carcinoma Lobular , Segunda Neoplasia Primária , Feminino , Humanos , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Lobular/secundário , Colo Sigmoide/patologia , Mastectomia , Segunda Neoplasia Primária/cirurgia , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Keratin 17 (K17) is regarded as a basal/myoepithelial cell keratin and is known to be inducible in activated keratinocytes. The high frequency of K17 expression in pancreaticobiliary nonmucinous adenocarcinoma or basal-like breast carcinoma has previously been described. However, its expression in gastric cancer (GC) is controversial. METHODS: We investigated the clinicopathological features and prognostic significance of 192 patients with GC by immunohistochemical staining of tissue microarrays. Analysis of epithelial markers including K17, K14, and K5/6, cell cycle-associated proteins p53, Ki-67, and 14-3-3 sigma, and mucinous phenotype markers including CD10, CDX2, MUC5AC, and MUC6 was performed. RESULTS: Cytoplasmic expression of K17 was observed in 95 (49.5%) of 192 patients with GC. K17 expression positively correlated with lymph node metastasis (P = 0.003) and advanced stages of the disease (P = 0.014). K17 expression was significantly correlated with 14-3-3 sigma expression (P < 0.001) and CD10 expression (P = 0.015). The overall survival rates of patients with K17-positive GC were significantly lower than those with negative K17 expression (50.5 vs. 71.1%, P = 0.004). Univariate analysis revealed that K17 expression confers a poor prognosis in patients with GC (P = 0.004), and it was also an independent prognostic factor in multivariate analysis (P = 0.049). CONCLUSIONS: K17 expression is correlated with tumor progression in GC and may serve as a biomarker for poor prognosis.
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Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Queratina-17/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas 14-3-3/metabolismo , Idoso , Fator de Transcrição CDX2 , Progressão da Doença , Exonucleases/metabolismo , Exorribonucleases , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucina-5AC/metabolismo , Mucina-6/metabolismo , Análise Multivariada , Estadiamento de Neoplasias , Neprilisina/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Proteína Supressora de Tumor p53/metabolismoRESUMO
Extramammary Paget's disease (EPD) is rare. We report a case of double anal canal cancers in a patient with a long history of perianal Paget's disease. The patient, a 68-year-old Japanese woman, refused surgery initially and was treated with electron beam therapy, which achieved remission. However, 6 years later, Paget's disease was found to be progressing again and double anal canal tumors were also detected in the proctos and external skin area. We performed abdominoperineal resection (Miles' operation) and lymph node dissection for the Paget's disease with double anal canal tumors. Immunohistochemical staining revealed cytokeratin (CK)-20 expression in the adenocarcinomas and Paget's disease lesion, but not CK-7 or gross cystic disease fluid protein-15 expression. The lesion was joined to the carcinoma by a stalk. The immunohistochemistry results suggested secondary EPD, although it was originally considered to be Paget's carcinoma (primary EPD) based on the clinical history.
Assuntos
Adenocarcinoma/complicações , Neoplasias do Ânus/complicações , Neoplasias Primárias Múltiplas/patologia , Doença de Paget Extramamária/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Primárias Múltiplas/cirurgia , Doença de Paget Extramamária/patologia , Doença de Paget Extramamária/cirurgia , RecidivaRESUMO
BACKGROUND & AIMS: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non-neuroendocrine components. Although the coexistence pattern of neuroendocrine and non-neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract. METHODS: From 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals. RESULTS: Among the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ. CONCLUSIONS: These findings suggested a potential "paratransformation" or "bystander effect" in resident epithelium by NENs. Thus, "bystander carcinogenesis" could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract.
Assuntos
Adenocarcinoma , Tumores Neuroendócrinos , Neoplasias Gástricas , Carcinogênese , Epitélio/patologia , Humanos , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Neoplasias Gástricas/patologiaRESUMO
Peliosis hepatis is an extremely rare condition that may cause fatal hepatic hemorrhage and liver failure. We report a case of liver hemorrhage due to idiopathic peliosis hepatis. A 60-year-old woman was admitted to our hospital with slight right hypochondriac pain. She went into hemorrhagic shock, and computed tomography (CT) showed multiple low-density areas in the right liver with massive subcapsular blood collection. Selective transfemoral arteriography of the celiac artery revealed no signs of vascular malformation or tumor stain, but showed signs of pooling in the right posterior segmental artery. The artery was embolized with particles of gelatin sponge, and hemostatic control was successful. Although peliosis hepatis is extremely rare, the diagnosis is significant because of its urgent clinical status, and transarterial embolization is a useful and minimally invasive procedure for liver hemorrhage due to peliosis hepatis.