Telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts

BACKGROUND: Pancreatic serous cystadenoma, mucinous cystic neoplasms, ductal adenocarcinoma with cystic change, and pseudocysts are a spectrum of pancreatic cystic lesions. Their management strategy and prognosis are extremely diverse. Imaging study, cytology, and analysis of the tumor markers of cyst fluid are not always reliable in differentiation of these disease entities. MATERIALS AND METHODS: Fifteen patients with pancreatic cystic neoplasms (including six mucinous cystadenocarcinomas, two mucinous cystic neoplasms with borderline malignancy, two mucinous cystadenomas, and five serous cystadenomas), 4 patients with pancreatic ductal adenocarcinomas with cystic change, and 10 patients with pseudocysts were studied. Echo-guided or computed tomography-guided biopsies of pancreatic cystic lesions and their normal counterparts were conducted on all patients prior to operation or other management. The specimens were assayed for telomerase activity by using TRAP (telomere repeat amplification protocol). The level of telomerase activity in each specimen was semiquantitated as strong, moderate, weak, and none. The final diagnoses were made from histopathological examination of surgically resected or biopsied specimens. The efficacy of telomerase activity as a tumor marker to predict malignancy of pancreatic cystic lesions was evaluated. RESULTS: Three of the four pancreatic ductal adenocarcinomas with cystic change had strong or moderate telomerase activity; four of the six mucinous cystadenocarcinomas had moderate or weak telomerase activity; one of the two mucinous cystadenomas with borderline malignancy had weak telomerase activity; and none of their normal counterparts had detectable telomerase activity. In contrast, none of the two mucinous cystadenomas, five serous cystadenomas, and 10 pseudocysts had detectable telomerase activity. Based on these results, the sensitivity of telomerase activity for prediction of malignancy or premalignancy of pancreatic cystic lesions was 67%, the specificity was 100%, and the positive and negative predictive values were 1.0 and 0.81, respectively. The overall accuracy was 86%. CONCLUSIONS: The differential expressions of telomerase activity have been detected specifically in malignant and premalignant pancreatic cystic tumors, but not in benign cystic neoplasms or pseudocysts. The implications of these results are that telomerase activation takes part in the malignant transformation of pancreatic cystic neoplasms and that telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts.     

肾癌组织的端粒酶活性

目的探讨端粒酶活性与肾细胞癌之间的关系。方法采用改良ＴＲＡＰ法对３２例肾细胞癌组织及正常肾组织和可疑癌旁组织中端粒酶活性进行检测,同时了解其与临床生物学特征的关系。结果３２例肾细胞癌组织中端粒酶强阳性１７例,阳性１２例,阴性３例,阳性率９１％;３２例正常肾组织中端粒酶弱阳性者仅２例,阳性率６％;可疑癌旁组织阳性者６例,阳性率１９％。三组端粒酶活性比较,阳性率差异有显著性（Ｐ＜０．０１）。结论肾细胞癌组织中端粒酶活性检出率高,特异性强,无假阳性和假阴性。提示端粒酶活性检测可作为判断肾肿瘤恶性程度的标记物,并可能成为判断肾肿瘤预后的一项指标。     

神经上皮肿瘤中端粒酶活性及其调节

目的 研究神经上皮肿瘤的端粒酶活性及其RNA和人端粒酶逆转录酶（h TERT)的表达水平,为其临床诊断和治疗开拓思路。方法 改良端粒重复序列扩增法及RT－PCR法检测65例神经上皮肿瘤患者肿瘤标本的端粒酶活性及其RNA和hTERT表达水平,并与8例正常脑组织的标本进行对照。结果 神经上皮肿瘤端粒酶阳性率为61．5％（分别r＝0．607,r＝0．678,均P＜0．01）。结论 端粒酶活性及hTERT与神经上皮肿瘤恶性程度有关;hTERT是调节端粒酶活性的关键酶。     

Liver resection in benign and malignant tumors]

Benign tumors of the liver, circumscribed hepatomas and solitary hepatic metastases from colonic cancer are treated by partial liver resection. In case of colonic cancer the hepatic metastasis is resected in a second operation. 20 cases of hepatic resections are reported. 10 right hepatic lobectomies, 1 left hepatic lobectomy and 9 minor resections were performed. Of the 11 patients treated by hepatic lobectomy, one (or 9%) died in the postoperative period (within 30 days after operation). Of the other 9 patients undergoing minor resections there was no death.     

Telomerase activity in human renal cell carcinoma

PURPOSE: Telomerase activity has been detected in a wide variety of human tumors. The present study evaluated telomerase activity in association with the acquisition of renal cell carcinoma (RCC). METHODS: Telomerase activity was examined in 30 RCC and the adjacent normal kidney tissue, obtained as surgical specimens. The activity was assayed by polymerase chain reaction-based telomeric repeat amplification protocol assay. RESULTS: Among the 30 RCC, 18 (60%) displayed telomerase activity, whereas none of the normal tissue samples exhibited it. Subdivision of the tumors according to telomerase activity did not reveal any obvious difference in distribution with regard to tumor size, stage, histocytological subtype, or DNA-ploidy. However, a statistically significant relationship was found between the frequency of telomerase-positive activity and both serum immunosuppressive acidic protein level in the patient and tumor grade (P<0.05). There was no significant difference in the recurrent-free survival and the disease-specific survival between patients with positive telomerase activity and patients with negative activity. CONCLUSION: The present results indicate that telomerase activity might be related to the progression of RCC and thus a marker of malignant potential.     

Telomerase activity in human renal cell carcinoma

OBJECTIVE: To determine if telomerase activity plays an important role in the progression of renal cell carcinoma (RCC). MATERIALS AND METHODS: Telomerase activity was measured in 53 tissue samples of RCC (52 patients), 11 samples of normal renal tissue and six tissue samples from benign renal disease using a fluorescence-based telomeric repeat amplification protocol. The activity was assessed for associations with clinical and pathological variables of RCC. To examine the influence of telomerase activity on cell immortalization in vitro, primary cultures of RCC cells were produced; the maximum passage number beyond which cell culture could not be continued was compared with the associated telomerase activity. RESULTS: Among the tissue samples of benign renal disease, one from a patient with a hydronephrotic nonfunctioning kidney had detectable telomerase activity, whereas none of the normal renal tissues had. In 32 of the 53 RCC tissue samples (60%), telomerase activity was detectable, varying from 1.8 to 100.0 TPG units, but was not associated with any clinical or pathological variable such as clinical stage, tumour size, grade or pathological subtype. Telomerase activity also had no association with the maximum passage number of primary cell cultures. CONCLUSIONS: Telomerase activity may not be a prognostic marker for RCC. Alternative mechanism(s) which lengthen telomeres should be considered if maintaining telomere length is considered essential to tumour progression.     

Robotic hepatectomy for benign and malignant liver tumors

Minimally invasive hepatectomy for benign and malignant liver lesions has gained popularity in the past decade due to improved perioperative outcomes when     

Telomerase activity in periampullary tumors correlates with aggressive malignancy

OBJECTIVE: To determine the presence of telomerase activity in a variety of periampullary malignancies and pancreatic diseases and quantify its activity to establish any association with the stage or aggressiveness of malignancy. SUMMARY BACKGROUND DATA: Progressive shortening of telomeres, repetitive DNA sequences at the ends of chromosomes, plays a role in cell senescence. Telomerase catalyzes conservation of telomeric repeats and may promote cell immortality and hence malignancy. It is absent in normal tissues but upregulated in more than 80% of cancers. METHODS: Fresh specimens of 62 periampullary tumors were snap-frozen in liquid nitrogen and adjacent tissue was formalin-fixed for histopathology. The telomerase repeat amplification protocol (TRAP) was used to obtain telomerase DNA products. These were separated with gel electrophoresis, stained with SYBR green, and quantified by densitometry. Findings were confirmed with a fluorometric TRAP assay in which fluorescent primers specific for telomerase were selectively amplified in its presence. RESULTS: Telomerase activity was upregulated in 26 of 33 periampullary malignancies (79%): 17 of 21 pancreatic adenocarcinomas (81%), 2 of 2 cholangiocarcinomas, 2 of 2 duodenal carcinomas, and 5 of 8 ampullary carcinomas (63%). Poorly differentiated periampullary tumors had significantly higher telomerase activity than well-differentiated tumors, and tumors larger than 2 cm had significantly higher telomerase activity than those 2 cm or smaller. Pancreatic ductal adenocarcinomas with lymph node metastases had significantly greater activity than node-negative cancers. Two of 11 intraductal papillary mucinous tumors were positive for telomerase activity, but only in foci of invasive carcinoma. Chronic pancreatitis (n = 7), serous cystadenomas (n = 5), benign mucinous cystic neoplasms (n = 4), neuroendocrine cancer (n = 1), and acinar cell carcinoma (n = 1) had no detectable telomerase activity. CONCLUSION: Telomerase activity is common in periampullary carcinomas. The magnitude of activity correlates with aggressiveness in pancreatic adenocarcinoma and may prove useful as a molecular index for biologic staging.     

Cellular DNA profiles of benign and malignant adrenocortical tumors

We evaluated the DNA content of 43 adrenocortical neoplasms by flow cytometry and related it to histopathologic criteria of malignancy and survival. Tumor tissue was selected from paraffin blocks and processed by a modification of the Hedley technique. The tumors were classified as adenomas and carcinomas by the criteria of Weiss. Aneuploid stem-lines were identified in nine of 13 (69%) of the carcinomas and in six of 30 (20%) of the adenomas. Five of the six patients with aneuploid adenomas are alive and well (mean follow-up, 59 months); the sixth was lost to follow-up. Although there was a significant correlation between ploidy and histologic diagnosis (p = 0.041), the sensitivity and specificity of aneuploidy for predicting clinical outcome were only 56% and 65%, respectively. In addition, there was no significant difference in survival between patients with diploid versus aneuploid tumors, despite a highly statistically significant difference in survival between patients with a histologic diagnosis of adenoma versus carcinoma (p = 0.00080). We found correlations between ploidy and tumor size, mitotic rate, and nuclear grade (p = 0.0033, p = 0.0017, and p = 0.018, respectively). There was also a significant correlation between the proliferation fraction of a tumor and its nuclear grade (p = .0093), but not its mitotic count or clinical outcome. Because both adrenal adenomas and carcinomas may contain abnormal DNA stem-lines, ploidy alone is not a reliable discriminator in individual cases.