Primary large cell neuroendocrine carcinoma of the urinary bladder

Primary large cell neuroendocrine carcinomas (LCNEC) of the urinary bladder are rare. Reported herein is a case of a primary, pure LCNEC occurring in a man. The patient was a 32-year-old man who presented with hematuria of 1 week's duration. On cystoscopic examination, a solitary mass measuring 3 cm in diameter was detected protruding from the anterosuperior wall of the urinary bladder. Two months after the primary transurethral resection, significant regrowth of the remnant mass was noted on CT, and the patient underwent a partial cystectomy. A diagnosis of LCNEC was made based upon histological and immunohistochemical findings. Tumor cells were positive for synaptophysin, chromogranin A, CD56, epithelial membrane antigen, and cytokeratin. Histologically, the tumor penetrated the deep muscle and perivesical fat. In spite of three cycles of chemotherapy, the patient developed multiple metastases in the lung and liver 10 months postoperatively. LCNEC of the urinary bladder are uncommon entities, which have a possible fatal outcome.     

Expression of somatostatin type 2A receptor correlates with estrogen receptor in human breast carcinoma

Somatostatin type 2A receptor (sstr2A) has been shown to be directly involved in the transduction of antiproliferative effects and also to be the most predominant sstr subtype in human normal breast epithelium, as well as in human breast carcinoma. We investigated the immunoreactivity of sstr2A in 34 cases of human breast carcinoma and correlated these findings with the immunoreactivity of the estrogen receptor (ER), epidermal growth factor receptor (EGFR), transforming growth factor α(TGFα) and insulin like growth factor I (IGF-I). We detected sstr2A immunoreactivity in normal mammary tissue, and in 27 of 34 (79%) breast carcinomas. The sstr2A immunoreactivity was localized on the cellular membrane, however, weak cytoplasmic immunoreactivity was also observed. Sstr2A immunoreactivity was heterogenously distributed in the whole tumor section. There was a statistically significant correlation between sstr2A and ER immunoreactivity in the same tumor. No statistically significant correlation was found between sstr2A immunoreactivity and immunoreactivity for EGFR, TGFα and IGF-I or the patients' age.     

Expression of erythropoietin and neuroendocrine markers in clear cell renal cell carcinoma

The aim of the study was to investigate the expression of erythropoietin and neuroendocrine markers in clear cell renal cell carcinoma (CCRCC). We retrospectively reviewed the medical records and re‐evaluated histopathological specimens of 33 patients with CCRCC and compared with those of 11 cases of non‐CCRCC. All patients were treated with a partial or radical nephrectomy at St. Olavs Hospital, Trondheim University Hospital, between 2010 and 2016. Thirty‐three patients who were diagnosed with CCRCC had a total of 35 tumours, where 34 of the tumours were CCRCC and one was papillary adenoma. Thirty‐three (97%) of 34 CCRCCs were positive for erythropoietin, and the same 33 (97%) tumours demonstrated strong expression for neuron‐specific enolase (NSE). Two (6%) of 34 CCRCCs had a positive reaction for synaptophysin, and three (9%) of 34 were positive for CD56. Erythropoietin and NSE were negative in non‐CCRCCs, and chromogranin A was negative in all tumours. The above findings suggest that there is a strong association between CCRCC and the expression of erythropoietin and NSE.     

Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid‐rich hepatocellular carcinoma

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich‐hepatocellular carcinoma (HCC) was challenging. The patient was a 50‐year‐old woman in whom a 3‐cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well‐demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid‐rich type HCC because it stained positive for Hep Par1, but negative for arginase‐1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF‐1 and 3β‐HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase‐1 is to rule out the possibility of lipid‐rich HCC.     

CD15 mRNA在原发性肝细胞癌中的表达及其预后意义

目的：研究CD15mRNA表达与原发性肝细胞癌（HCC）侵袭转移和预后关系及与CD44v6和nm23H1的mRNA表达相关性。方法：应用原位杂交和免疫组织化学方法，检测分析HCC组织中CD15mRNA及其蛋白、CD44v6及nm23H的mRNA表达。结果：99例HCC中，CD15mRNA及其 蛋白、CD44和nm23H1的mRNA表达阳性率分别为38．4％、36．7％、41．4％和76．8％。CD15mRNA表达与其 蛋白表达一致，与CD44v6 mRNA表达呈正相关，与nm23H1 mRNA表达呈负相关。CD15mRNA及其蛋白、CD44和nm23H1的mRNA表达均与HCC侵袭转移倾向和患者预后相关。结论：检测CD15表达有可能成为HCC侵袭转移和预后判断的一项新的病理生物学指标。     

Endocrine liver tumour differential diagnosis from hepatocellular carcinoma

A liver tumour, initially diagnosed by light microscopy as a hepatocellular carcinoma, was later shown to be endocrine by argyrophilia and electron microscopy. It was tested by immunohistochemistry for insulin, glucagon, gastrin, VIP, pancreatic polypeptide, glicentin, C-peptide and somatostatin. A few cells were shown to contain somatostatin, but the secretion product in most of the cells was not identified. The patient is well, without any sign of endocrine disturbances, 18 months after the operation.     

Primary hepatic carcinoid and neuroendocrine carcinoma: Clinicopathological and immunohistochemical study of five cases

Primary hepatic carcinoid and neuroendocrine carcinoma (NEC) are rare tumors. We experienced three carcinoids and two NEC originating in the liver during the past 25 years and attempted to elucidate the clinicopathological and immunohistochemical features of these tumors. The patients had no endocrine symptoms despite two of them having elevated plasma serotonin. Three of the five patients died of the tumor after operation with an average survival time of 20.6 months. All tumors were large (up to 26 cm in diameter), four of them solitary and one multinodular, and were not associated with liver cirrhosis. The carcinoid tumors showed insular, trabecular or glandular arrangement of argyrophilic cells, whereas in the NEC this histological pattern was distorted. Immunohistochemically the tumors showed expression of chromogranin A (all cases), chromogranin B (three cases), pancreastatin and chromostatin (four cases, respectively), prohormone convertase PC3 (three cases), carcinoembryonic antigen (CEA) and CA19-9 (two cases), cytokeratin 56 kDa (three cases), 160 kDa neurofilament (two cases) and neuron-specific enolase (two cases). Serotonin and glucagon were sporadically detected in two tumors. The most useful marker to confirm the diagnosis was chromogranin A, which was cleaved to pancreastatin and chromostatin in the tumor tissue, and was more reliable than other markers of neuroendocrine differentiation.     

Clinicopathological value of somatostatin type 2A and estrogen receptor immunoreactivity in human breast carcinoma

Somatostatin type 2A (sstr2A) and estrogen receptor (ER) are interrelated regulatory receptors present in normal breast epithelium and in a population of breast carcinomas. ER mediates growth stimulatory effects of estrogens whereas sstr2A mediates growth inhibitory actions of somatostatin. However, much work has been devoted to elucidate the biological role of ER, little is known about sstr2A in breast cancer. In the present study we examined immunoreactivity of sstr2A and ER in 64 breast carcinomas in correlation with tumor size and histological grade (HG), presence of lymph node metastasis (LNM), Nottingham prognostic index (NPI), and the patients' age. ER and sstr2A immunoreactivity were present in 78% and 63% of the breast carcinomas, respectively. Ninety percent of tumors immunoreactive for sstr2A were simultaneously immunoreactive for ER. ER immunoreactivity correlated significantly with lower HG (p=0.03) and better NPI (p=0.02). sstr2 A immunoreactivity correlated significantly with lower HG (p=0.012) but not with NPI (p=0.26). There was no correlation of sstr2A immunoreactivity and tumor size, patients' chronological age or LNM. The results confirm prognostic value of ER immunohistochemistry in breast carcinoma. However sstr2A cannot substitute ER for prognostic evaluation, sstr2A immunoreactivity being significantly associated with lower HG seems to represent an independent prognostic factor in breast carcinoma.     

肝细胞性肝癌中MAZ基因的表达及意义

目的探讨MAZ基因在肝细胞性肝癌(hepatocellular carcinoma,HCC)及其癌旁正常组织中的表达,分析其与HCC各临床病理特征及预后的关系。方法采用组织芯片技术和免疫组化法检测75例HCC及其对应癌旁正常组织中MAZ基因的表达,分析其与HCC临床病理特征及与患者预后的关系。结果 MAZ在HCC中的表达(48%,36/75)明显高于其癌旁正常组织(22.67%,17/75),组间比较差异有统计学意义(P0.05)。MAZ表达与HCC患者性别、年龄、病理分级、临床分期、TNM分期、是否合并肝硬化、是否合并乙肝病毒感染、是否有肝癌家族史以及血清AFP、CEA、γ-GT、ALT、AST和ALB水平、是否有淋巴结转移等均无明显相关性,而与肿瘤直径、吸烟与否、饮酒与否显著相关(P0.05)。HCC中MAZ阳性组和阴性组的累计生存率差异有显著性(P0.05),MAZ阳性组患者的术后无瘤生存时间明显低于阴性组,提示MAZ表达上调可能导致患者的预后更差。结论 MAZ基因表达上调可能与HCC的发生、发展密切相关。     

肝细胞肝癌中LOXL2过表达与转移及预后的相关性

目的检测LOXL2和上皮-间质转化(epithelial-mesenchymal transition,EMT)相关基因在肝细胞肝癌组织中的表达,揭示LOXL2和EMT之间的关系,从而阐明LOXL2对肝细胞肝癌转移及预后的影响。方法采用免疫组化法检测106例肝细胞肝癌组织中LOXL2、Snail、E-cadherin和vimentin的表达,采用CD31/PAS双染法检测肝细胞肝癌中血管生成拟态(vasculogenic mimicry,VM)的情况,并分析LOXL2与EMT分子之间的相关性。采用χ~2和Spearman相关分析来分析其与VM形成和临床病理资料之间的关系。采用Kaplan-Meier法评估LOXL2对肝细胞肝癌患者生存时间的影响。采用Cox比例风险模型分析LOXL2对肝细胞肝癌预后的价值。结果 LOXL2表达与Snail、vimentin和E-cadherin的表达密切相关,LOXL2表达与肿瘤分级和VM形成相关。LOXL2阳性表达或VM形成的患者其总体生存期和无病生存期比LOXL2阴性表达和无VM形成的患者短(P0.05);同时具有LOXL2阳性表达和VM形成的患者预后最差。结论 LOXL2表达与EMT标记蛋白相关,并与肝细胞肝癌分级和VM形成密切相关,且对预后有一定的影响。     

Correlation of adrenomedullin with the erythropoietin receptor and microvessel density in hepatocellular carcinoma

Introduction

Uncontrolled angiogenesis plays an essential role in the occurrence, metastasis and malignant progression of hepatocellular carcinoma (HCC). This study aimed to investigate the expression of adrenomedullin (ADM) in human HCC and its correlation with the expression of erythropoietin receptor (EPOR), microvessel density (MVD) and the tumor pathological characteristics.

Material and methods

Fresh tumor tissues were obtained from 30 HCC patients after hepatectomy. Ten cirrhotic and 10 normal liver tissues were included as controls. Expression of ADM and EPOR was determined by real-time PCR. The MVD was determined by counting the number of microvessels.

Results

The MVD and the mRNA levels of ADM and EPOR in cancer tissues were significantly higher than those in the non-cancer tissues (p < 0.05). Expression of ADM was significantly correlated with the MVD and EPOR (r = 0.68 and 0.74, p < 0.01). Adrenomedullin and EPOR mRNA levels in HCC tissues were correlated with capsule invasion, pathological differentiation and tumor metastasis (p < 0.05).

Conclusions

Our findings suggest that ADM and EPOR may serve as new regulatory factors involved in angiogenesis of HCC and represent novel targets for the treatment of HCC.     

Cystatin B在肝癌组织中的表达及其与患者预后的关联

目的：研究Cystatin B(CSTB)在肝癌组织中的表达及其与肝癌患者预后的相关性。方法：利用Real-time PCR和Western blot分别检测肝癌病人癌与癌旁组织中CSTB mRNA水平和蛋白的表达,进一步通过免疫组织化学法检测组织芯片中CSTB表达并分析其与肝癌临床特征的关系。采用Kaplan-Meier生存分析法分析CSTB与肝癌预后的关系。结果：在肝癌组织中CSTB mRNA水平和蛋白水平的表达明显高于癌旁(P<0.05);生存分析发现CSTB高表达肝癌患者比低表达的患者更易复发且总体生存期短(P值均小于0.05);CSTB的表达与年龄、性别、BCLC分级以及肿瘤大小差异均无统计学意义(P值均大于0.05),CSTB高表达的患者更容易形成门脉癌栓(P<0.05)。结论：CSTB在肝细胞癌组织中高表达,其表达水平与肝癌病人预后有关,有望成为肝癌预后指标。