胃异型增生上皮、胃腺癌组织中神经内分泌与p53蛋白的检测

目的　探讨胃异型增生上皮、胃腺癌组织中神经内分泌和 p5 3蛋白的表达及意义。 方法　应用免疫组织化学法检测10例正常胃黏膜、63例癌旁低度异型增生、2 6例高度异型增生及相应胃腺癌组织中嗜铬粒蛋白A (CgA )、突触素 (Syn)、神经元特异性烯醇化酶 (NSE)和p5 3蛋白的表达。结果　癌旁低度异型增生、高度异型增生及相应胃腺癌组织中 ,CgA、Syn、NSE和 p5 3蛋白阳性表达率均有非常显著性差异 (P <0 .0 1)。结论　胃异型增生上皮和胃腺癌伴神经内分泌是 1种常见的现象 ,它和 p5 3蛋白在胃腺癌的发生发展中的作用可能有所不同     

突变型p53基因与肝细胞癌组织学分级、转移、肿块大小和包膜形成的相关性研究

目的：探讨突变型p53基因与肝细胞癌组织学分级、转移、肿块大小和包膜形成的相关性。方法：随机选择41例肝细胞肝癌患者的癌和癌旁肝组织标本，SP法检测其p53蛋白表达，分析突变型p53基因与肝细胞癌组织学分级、转移、肿块大小和包膜形成的相关性。结果．p53在癌和癌旁肝组织中阳性表达率分别为43．9％和6．67％，两者比较，差异显著（P〈0．01）；p53蛋白阳性表达率，Ⅲ-Ⅳ级肝癌明显高于Ⅰ～Ⅱ级肝癌，发生转移（血道或淋巴道转移）肝癌明显高于未发生转移（血道或淋巴道转移）肝癌，两者之间比较，差异有显著性意义（P〈0．05）；但p53蛋白阳性表达率与肝癌组织大小和其是否有包膜无关（P〉0．05）。结论：突变型p53基因与肝细胞癌组织学分级、转移密切相关，但与肝癌组织大小和包膜形成无关。     

Neuroendocrine tumor metastatic to the orbit treated with radiotherapy

Neuroendocrine tumors are rare neoplasms that infrequently metastasize to the orbit.Given that patients with these tumors may have prolonged survival despite dissemination,maintaining quality of life by providing early diagnosis and effective treatment to preserve vision and comfort is a fundamental issue.We report the case of a79-year old woman who presented with well-differentiated metastatic neuroendocrine tumor to the liver with no carcinoid syndrome and was started on intramuscular long-acting octreotide with disease stabilization.Two years later she developed right-sided diplopia associated with mild eye discomfort,proptosis and reddening.An magnetic resonance imaging showed a 2.1 cm mass in the right orbit and further biopsy confirmed a neuroendocrine tumor metastasis.The patient was treated with a four-week course of stereotactic radiotherapy to the right orbital metastasis(4000 cGy in 20 fractions)with minor conjunctivitis as the only side effect.Eighteen months later,she remains well with no visual loss.     

Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors

IntroductionRecent classification of neuroendocrine neoplasms has defined well‐differentiated high‐grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well‐described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens.Materials and MethodsThis was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients’ demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression‐free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR).ResultsTreatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki‐67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum‐etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96–16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months.ConclusionAmong patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short‐lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy.Implications for PracticeHigh‐grade well‐differentiated neuroendocrine tumors (NET G3) are considered a different entity from low‐grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well‐differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.     

Pituitary metastasis from medullary carcinoma of thyroid: case report and review of literature

Pituitary is a rare site for metastases from thyroid cancer. Most reported cases have been of papillary and follicular carcinoma. Metastases from medullary thyroid carcinoma have not been reported. We report a case of intrapituitary metastasis from medullary carcinoma thyroid in a 38-year-old male, who had been operated for pituitary adenoma 5 years earlier. At the time of presentation in Nov 2006, he had visual field defects and a painless thyroid nodule. Further evaluation revealed medullary carcinoma thyroid, cervical and mediastinal lymphadenopathy, elevated serum calcitonin levels, and lobulated pituitary tumor. After surgical excision of thyroid and lymph node clearance, he underwent craniotomy and subfrontal excision of pituitary tumor. All the tumors were of identical histology, i.e., medullary carcinoma thyroid. Pituitary tumor was positive for calcitonin.     

Prostate cancer metastasis to thyroid gland

Metastases to the thyroid gland are rarely encountered in clinical practice. They may originate from various primary sites, mainly kidney, lung, breast, esophagus and uterus. Prostate cancer is one of the most frequent malignancies in men. It generally has a favorable course, and autopsy series have shown occult prostate cancer in many subjects, especially in aged males. However, prostate cancer sometimes exhibits an aggressive behavior and cases with a poor prognosis have been reported. Occasional reports of metastasis from prostate cancer to the thyroid gland have been documented. We describe the case of a 73-year-old patient presenting with thyroid metastasis from long-standing prostate cancer.     

神经内分泌细胞与乳腺癌患者预后因素的关系

目的 探讨乳腺癌中神经内分泌（NE）细胞的存在及其与临床预后有关指标的关系。方法 收集乳腺癌根治术组织标本53例,采用免疫组织化学法标记1组NE分化的指标：NSE、Syn、CgA以检测NE细胞的存在,同时行电镜检查证实。结果 53例乳腺癌中,NSE、Syn、CgA3种标志物均阳性14例,占26．4％,电镜检查找到肿瘤细胞中存在神经内分泌颗粒。NE阳性者淋巴结转移率高于NE阴性者,其pS2蛋白和nm23-HI表达均低于NE阴性者。结论 根据WHO分类的病理类型乳腺癌中,部分可存在神经内分泌细胞,它们属乳腺癌异质性的表现,具有与一般病理类型乳腺癌不完全一致的生物学行为,在乳腺癌术后治疗方案的决策上需引起应有的重视。     

Rectal adenocarcinoma metastatic to the thyroid gland

Metastatic lesions in the thyroid are rarely reported, although microscopic metastasis to the thyroid gland is not uncommon, having been found in 4%–9% of autopsy studies. Here we present a case of rectal adenocarcinoma metastatic to the thyroid. A 28-year-old woman was admitted to the hospital for persistent anal bleeding, weight loss, and dysphagia. Physical and imaging examinations disclosed a nodule in the left lobe of the thyroid and rectal cancer in the upper rectum. Fine-needle aspiration cytology of the thyroid nodule revealed adenocarcinoma, which was consistent with a diagnosis of metastasis from the primary rectal adenocarcinoma to the thyroid. The patient died of tumor recurrence 6 months after surgery. Thyroid meta-stasis from colon and rectal carcinoma is rare, with only 11 cases appearing in the literature since 1990. The rarity and prognosis of thyroid metastasis from colon carcinoma are discussed here.     

乳腺癌伴神经内分泌分化及与预后的关系

目的　探讨乳腺癌中神经内分泌细胞的存在及与预后的关系。方法　采用免疫组化S P法对 5 8例乳腺癌手术标本进行神经内分泌抗体NSE ,Sy ,CgA的测定 ,并用电镜检查证实之 ,同时进行淋巴结转移情况分析。结果　 5 8例乳腺癌病人中NSE ,Sy ,CgA三种抗体表达阳性者 14例 ,占 2 4% ,电镜检查找见肿瘤细胞中存在神经内分泌颗粒。NE+ 者淋巴结转移率 (5 7% )较NE-者淋巴结转移率为高 (2 7% ) ,P <0 0 5。结论　乳腺癌伴有神经内分泌分化是肿瘤异质性的表现 ,是乳腺癌的一种特殊类型 ,具有与一般类型乳腺癌不完全一致的生物学行为 ,在乳腺癌术后治疗方案的决策上需引起应有的重视。     

Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic Retrospective Study of 31 Cases with Prognostic Implications

Abstract

The present study describes 31 clinical cases of neuroendocrine cervical carcinoma (NECC) treated at Mackay Memorial Hospital between January 1, 1991 and October 31, 2003. There are two cases of atypical carcinoid tumor (ACT), four cases of large-cell neuroendocrine carcinoma (LCNEC), and 25 cases of small-cell neuroendocrine carcinoma (SCNEC). Overall survival did not differ significantly in relation to surgery, tumor histology, age, FIGO stages, chemotherapeutic regimens or lymph node involvement. The specimens available did not permit HPV (human papillomavirus)-DNA analysis in 5 cases (5/31, 9.7%). The HPV viral infection was absent in 8 cases (8/31, 26%); 17 cases of HPV-18 (17/31); and 1 case of HPV-16 (1/31). The prognosis between mixed and pure type histologic patterns is not significant. The mean survival time for all patients was 32.3 months. The 2-year and 5-year survival rates were 54.8% and 31.5% for all patients. The results of this study reaffirm the biologically aggressive nature of this rare malignancy, its low survival rate, and its very unpredictable prognostic factors. Effective treatments of neuroendocrine cervical tumor still remain inconclusive. Further efforts are still required to identify prognostic factors for this uncommon disease.     

Isolated metastasis of lung cancer to the thyroid gland

A 67-year-old man with lung cancer developed an isolated metastasis to the thyroid gland. The patient had undergone a right upper lobectomy, followed by chemotherapy consisting of cisplatin and etoposide based on post-surgical diagnosis of small cell lung cancer. Four years later, he had an isolated metastasis to the thyroid gland. The patient underwent a metastasectomy and adjuvant chemotherapy including cisplatin and irinotecan. The cancer cells in resected thyroid tumor had large nuclei and cytoplasm, and expressed the neuroendocrine markers, CD56 and chromogranin A. Retrospectively, the primary lung cancer consisted of both small cell and large cell cancer, and the latter was consistent with the pathological finding of the thyroid tumor. This is the first report to document an isolated recurrence of the lung cancer to the thyroid.     

Neuroendocrine differentiation in gastric adenocarcinomas; correlation with tumor stage and expression of VEGF and p53

Studies on neuroendocrine differentiation (NED) in conventional gastric adenocarcinomas and its significance on tumor behavior are limited. Our aim was to search for the expression of neuroendocrine differentiation in conventional gastric adenocarcinomas and correlate it with tumor type, stage and expression of VEGF and p53. Forty-two gastrectomy specimens with gastric adenocarcinoma were stained with chromogranin A to detect neuroendocrine differentiation and 45% of the cases were found to be NED (+). No significant correlation was found between NED and tumor type. However, NED was more frequent in advanced stage cases independently of tumor type. VEGF expression was also considerably more frequent in NED (+) tumors compared to NED (−) ones (84% vs. 56%). Moreover, we found a significant correlation between NED and the presence of lymph node metastases. P53 expression in NED (+) tumors was 68%. There was no significant correlation between VEGF and p53 in NED (+) cases. In conclusion, neuroendocrine differentiation is a frequent finding in conventional gastric adenocarcinomas, and although it does not seem to play a specific role in tumor progression, it seems that neuroendocrine cells are one of the factors contributing to angiogenesis by expressing VEGF, especially in advanced stage cases, affecting the incidence of lymph node metastases. Further studies with larger series should be performed to confirm this observation.     

p53基因在甲状腺癌中的突变研究

目的：为探讨p53基因突变与甲状腺癌的发生、发展及预后的关系。方法：应用PCR单链构象多态性（SSCP）分析技术,对p53基因第7,8外显子突变进行了检测和分析。结果：在37例甲状腺癌中有11例在第7.8外显子发生突变,突变率为29.9％。p53基因突变在复发的患者中显著高于未复发的患者;p53基因突变与转移、组织学类型和分化状况无显著差异。结论：p53基因的突变可能与甲状腺癌患者预后有关。     

p16和p53抑癌基因产物在胰腺癌中表达的研究

目的 :探讨抑癌基因p16和p53在胰腺癌中的表达与临床病理的关系及其在胰腺癌发病机制中所起作用。方法 :应用免疫组织化学方法检测 50例胰腺癌p16和p53蛋白的表达水平。结果 :p16蛋白表达阳性率为 4 8% ,组织学Ⅰ级阳性率 (80 % )显著高于Ⅱ级 (50 % )和Ⅲ级 (2 5% ) ;临床Ⅰ期阳性率 (80 % )显著高于Ⅱ期 (38 9% )和Ⅲ Ⅳ期 (2 9 4 % )。p53蛋白表达阳性率为 54% ,临床Ⅰ期阳性率(2 6 7% )却显著低于Ⅱ期 (6 1 1% )和Ⅲ Ⅳ期 (70 6 % )。p16发生缺失同时伴有p53基因突变 ,即p16(- )p53( )共 17例 ,占 34%。结论 :胰腺癌发生中存在p16抑制途径和p53抑制途径改变 ,p16和p53蛋白异常在胰腺癌发生进展中起着重要作用。     

Lymph node metastasis in hereditary medullary thyroid cancer is independent of the underlying RET germline mutation

Although the onset of hereditary medullary thyroid cancer (MTC) depends on mutational risk, the impact of that risk on lymph node metastasis is unclear.Included in this investigation were 387 carriers of RET germline mutations with node-negative MTC (201 carriers) or node-positive MTC (186 carriers).Age at thyroidectomy increased significantly from highest (p.Met918Thr; 45 carriers), high (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr; 138 carriers) and moderate-high risk (p.Cys609/611/618/620Arg/Gly/Phe/Ser/Trp/Tyr; 93 carriers) to low-moderate risk (p.Glu768Asp, p. Leu790Phe, p. Val804Leu/Met, p. Ser891Ala; 111 carriers).In contrast, tumor progression to lymph node metastasis was similar, taking 8.6–9.1 years with moderate risk mutations and 13.6–14.5 years with high and highest risk mutations. Primary tumor size across the mutational risk spectrum changed little, measuring 18.1–22.1 mm with and 2.7–7.3 mm without lymph node metastasis.Because the biological behavior of hereditary MTC is similar after disease onset, equal treatment of comparable tumors is warranted regardless of the underlying RET mutation.     

甲状腺髓样癌的预后因素分析

目的　评估影响甲状腺髓样癌预后的因素。方法　采用统计学单、多因素分析研究本院初治 5 3例甲状腺髓样癌的预后因素。结果　总的 5年、10年、15年生存率各自为 6 6 %、5 9.9%和 5 3.2 %。单因素分析示 :原发灶累及双侧 ,原发灶 >4cm ,病灶外侵甲状腺包膜 ,无腹泻症状 ,远处转移 ,手术彻底程度影响预后。多因素示 :手术彻底程度是影响甲状腺髓样癌生存的独立预后因素。结论　手术彻底程度是影响甲状腺髓样癌生存的独立预后因素。