Telomerase expression as a marker in prostate cancer: correlation to clinicopathologic predictors

The aim of this study was to investigate by an in situ hybridization procedure the Telomerase expression as a marker in prostate cancer and to correlate these results with several prognostic factors concerning this cancer. Imprint smear samples were obtained from 70 prostates removed from patients who underwent radical prostatectomy for prostate adenocarcinoma. Telomerase expression in cancerous prostate smears was studied using an in situ hybridization procedure. The results were correlated with prognostic factors such as pathologic staging, Gleason grading, PSA serum levels and tumour differentiation. Positive Telomerase expression was detected in 88.6% prostate cancer smears. Telomerase expression was significantly correlated with the Gleason score (p < 0.001), tumour differentiation (p < 0.001) and PSA serum levels (p = 0.002). The distribution of Telomerase expression according to histopathological staging was not statistically significant (p < 0.56). In conclusion Telomerase expression could be a marker indicating the malignant potential of prostate cancer.     

Prognostic value and clinicopathologic correlation of p53 gene mutations and nuclear DNA content in human lung cancer: A prospective study

The aim of this prospective study was to determine whether use of a combination of biomarkers, p53 and nuclear DNA content, led to improved prognosis and Clinicopathologic correlation in human non-small cell lung cancer. Nineteen patients undergoing curative resection of primary non-small cell lung cancer were evaluated. Resected tumors were studied by polymerase chain reaction/single strand conformation polymorphism analysis (p53 gene mutations), flow cytometry (nuclear DNA content and cell cycle analysis), and immunohistochemically (p53 oncoprotein). Histologically normal lung was used as an internal control for each patient. Minimum postoperative follow-up was 4 years. p53 gene mutations (5/19 tumors; 26%), tumor ploidy (5/19 diploid), patterns of immunoreactivity, or combination of biomarkers did not appear to correlate with clinicopathologic findings or clinical outcome. Two of three patients with associated second primary malignancies, had squamous cell diploid tumors with p53 gene mutations. We conclude that p53 gene mutations and tumor ploidy may represent different biologic markers for human nonsmall cell lung cancer. Although trends in improved predictive accuracy were not seen when both markers were incorporated into the tumor analysis, flow cytometry and molecular analysis of the p53 gene may identify patients at increased risk of the development of a second primary maligmancy. © 1994 Wiley-Liss, Inc.     

Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters.

The polyamines putrescine, spermidine, and spermine and ornithine decarboxylase (ODC), the rate-limiting enzyme in their biosynthetic pathway, play an important role in cell proliferation, differentiation, and transformation. In the present study, we have analyzed polyamine concentrations and ODC activity in samples from benign breast diseases (n = 36), benign breast tissue adjacent to the primary carcinoma (n = 19), and breast carcinoma (n = 104). ODC activity in primary carcinoma was significantly higher (2.42 +/- 0.22 nmol CO2/h g; P < 0.001) than that found in benign breast (0.62 +/- 0.15 nmol CO2/h g) or in breast tissue adjacent to the primary carcinoma (0.52 +/- 0.16 nmol CO2/h g). The total polyamine content of breast cancer tissues was higher than in benign breast diseases (704.3 +/- 38.3 nmol/g wet weight versus 295.8 +/- 27.4 nmol/g wet weight) and correlated well with ODC activity (Pearson, r = 0.42; P < 0.001). ODC activity correlated with histological grade, peritumoral lymphatic or blood vessel invasion, S-phase fraction, and cathepsin D. Total polyamine concentration increased with S-phase fraction, cathepsin D, and aneuploidy. No significant correlation was found between ODC or polyamines and tumor size, lymph node involvement, or steroid receptor status. A major finding in our study was that ODC activity was an independent prognostic factor for recurrence and death. The results indicate that the estimation of ODC activity and polyamines in human breast carcinoma might be useful to determine tumor aggressiveness and suggest that ODC may have a potential value as both a prognostic factor and a chemoprevention target in human breast cancer.     

Endometrioid adenocarcinoma of the prostate: A clinicopathologic and immunohistochemical study

On retrospective review of the tumor registry files between 1979 and 1992 at the North Iowa Medical Center, six cases of endometrioid adenocarcinoma of the prostate were identified among 1582 cases of prostatic carcinoma. Along with long-term clinicopathologic follow-up, immunohistochemical studies of the prostatic tumor tissues were performed. All six cases of endometrioid carcinoma, together with control cases of benign prostatic hypertrophy (BPH) and ordinary adenocarcinoma of the prostate had unequivocal diffuse positive staining for PSA and similar reactivity to ER-D5 and PS2. Thus, endometrioid carcinoma is most likely derived from the prostate or prostatic urethral duct rather than the utricle. However, due to its unusual initial clinical manifestations, biological behavior, and distinctive histomorphology, the term “endometrioid adenocarcinoma of the prostate” is worth preserving. © Wiley-Liss, Inc.     

Prognostic significance of neuroendocrine differentiation in prostate adenocarcinoma

Much progress has been made toward an understanding of the development and progression of prostate cancer (PC) and the factors that drive the development of androgen independence. Neuroendocrine (NE) cells may provide an intriguing link between NE cell differentiation (NED) and tumor progression in PC. NED in PC generally confers a more aggressive clinical behavior and less favorable prognosis than conventional PC. In this article, we review the known functions of NE cells in PC and discuss the current knowledge on stimulation of cancer proliferation, invasion, apoptosis resistance, serum and immunohistochemical markers, and the prognostic significance of NED in human PC.     

Prognostic value of DNA ploidy and automated assessment of stroma fraction in prostate cancer

The combination of DNA ploidy and automatically estimated stroma fraction has been shown to correlate with recurrence and cancer death in colorectal cancer. We aimed to extend this observation and evaluate the prognostic importance of this combined marker in prostate cancer. DNA ploidy status was determined by image cytometry and the stroma fraction was estimated automatically on hematoxylin and eosin stained sections in three tumor samples from each patient to account for tumor heterogeneity. The optimal threshold for low (≤56%) and high (>56%) stroma fraction was identified in a discovery cohort (n = 253). The combined marker was validated in an independent patient cohort (n = 259) with biochemical recurrence as endpoint. The combined marker predicted biochemical recurrence independently in the validation cohort. Multivariable analysis showed that the highest risk of recurrence was observed for patients with samples that had both non-diploid ploidy status and a high stroma fraction (hazard ratio: 2.51, 95% confidence interval: 1.18–5.34). In conclusion, we suggest the combination of DNA ploidy and automatically estimated stroma fraction as a prognostic marker for the risk stratification of prostate cancer patients. It may also be a potential generic marker as concurrent results have been described in colorectal cancer.     

食管胃结合部腺癌的预后分析

背景与目的:食管胃结合部腺癌(adenocarcinoma of gastroesophageal junction,AGEJ)的发病率逐步升高,且由于其解剖部位特殊,预后相对较差.本研究旨在总结复旦大学附属肿瘤医院外科治疗的AGEJ的临床资料,以探讨影响AGEJ术后生存的相关预后因素.方法:回顾性分析1996年1月1日-2005年9月31日间复旦大学附属肿瘤医院腹部外科收治的749例可切除的AGEJ病例的临床和病例资料,并对其进行随访.AJCC分期:Ⅰ期90例(12.0%),Ⅱ期165例(22.0%),Ⅲ期379例(50.6%),Ⅳ期115例(15.4%).手术根治率89.5%,R0根治切除率87.4%.生存率计算及生存曲线绘制采用Kaplan-Meier法,单因素预后分析采用Log-rank检验,多因素预后分析采用Cox比例风险模型.结果:本组病例的总体5年生存率为38.5%,中位生存期为38个月.手术性质、淋巴结清扫范围、胃体切除范围、联合胰脾切除、大体标本类型、肿瘤累及贲门、肿瘤部位、肿瘤最大径、分化程度、脉管侵犯、淋巴结阳性比、阳性切缘、肿瘤残留分级以及TNM分期在单因素分析中显示对预后有显著影响.胸腹联合手术与单纯进腹手术预后差异无统计学意义(38.3% vs 40.1,P=0.850).多因素分析结果显示肿瘤残留分级、脉管累及、淋巴结阳性比及TNM分期是独立的预后因素.结论:AGEJ的外科治疗中,手术入路的选择不影响患者的预后.手术应行标准D2淋巴清扫,并达到R0根治切除.联合胰脾切除疗效有待临床验证.病理检查中,应尽可能检出16枚以上的淋巴结,以保证分期的准确性.     

Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study

BackgroundNeoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC.MethodsIn total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients.ResultsAmong the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients.ConclusionsTRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.     

Prognostic value of lymph node evaluation in small bowel adenocarcinoma

BACKGROUND:

The presence of distant metastases and the completeness of resection are important prognostic factors in patients with small bowel adenocarcinoma (SBA); however, the influence of lymph node metastasis on patient outcome has not been well characterized. The objective of the current study was to evaluate the impact of the number of positive and negative lymph nodes on survival after curative resection.

METHODS:

Patients who had SBA diagnosed between 1988 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Cox proportional hazards regression analyses were performed after adjusting for age, sex, race, tumor stage, tumor grade, and primary site. Five‐year disease‐specific survival (DSS) was determined, all patients were categorized according to the total lymph nodes (TLNs) assessed, and patients with stage III disease also were categorized according to the number of positive lymph nodes (PLNs) and the PLN‐to‐TLN ratio (the lymph node ratio [LNR]).

RESULTS:

In total, 1991 patients (n = 1216 with stage I/II SBA and n = 775 with stage III SBA) were analyzed. Survival depended on the TLNs assessed. The 5‐year DSS rate for patients with stage II disease was associated with the TLNs assessed (44%, 69%, and 83% for 0 TLNs, 1‐7 TLNs, and >7 TLNs, respectively). The 5‐year DSS for patients with stage III disease was associated with the number of PLNs (58% and 37% for <3 PLNs and ≥3 PLNs, respectively). Among patients with stage III disease, the LNR was even more predictive of survival than stratification by the number of PLNs.

CONCLUSIONS:

Survival after surgical resection for stage I, II, and III SBA was associated with the TLNs assessed. Stratifying patients with stage III disease into those with <3 PLNs and ≥3 PLNs significantly improved prognostication. Cancer 2010. © 2010 American Cancer Society.     

Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma

The prognostic value of clinical features, qualitative and quantitative pathologic characteristics and steroid receptor incidence was evaluated in 50 patients with Stage I endometrial adenocarcinoma. It turned out that many of these features were prognostically important. Estrogen receptor content was not significantly associated with prognosis in our material, but patients with progesterone receptor positive lesions had a better survival than those in which the tumors were progesterone receptor negative. Multivariate analysis also clarified that only three features in combination had independent significance: mean shortest nuclear axis, DNA index, and depth of myometrial invasion (in sequence of decreasing importance). The prognostic rule consisting of these features overshadowed the value of all other features investigated. The overriding prognostic value of this highly reproducible rule was clear from the complete separation of 27 survivors and six nonsurvivors in the learning set of 33 patients. In an independent test set, all three nonsurvivors and 13 of the 14 survivors were correctly classified, thus confirming the accuracy and reliability of the developed rule to predict the outcome of future patients with Stage I endometrial adenocarcinoma.     

Ki-67预测肺腺癌患者预后价值的Meta分析

目的:通过Meta分析评估Ki-67能否作为判断肺腺癌患者预后的指标。方法:系统检索PubMed、EMBase和Cochrane数据库获得相关文章,提取文章信息并完成文章质量评价后,利用R 3.6.1软件评估Ki-67高表达对肺腺癌患者及其不同亚组预后的影响。结果:共纳入27篇文章的28项研究。结果显示,在肺腺癌患者中,Ki-67表达与总体生存期(overall survival,OS,HR:1.15,P=0.000 1)和无病生存期(disease-free survival,DFS,HR:2.12,P=0.000 3)呈负相关。种族方面,目前仅在亚洲患者中提示Ki-67高表达患者的预后较差;而在不同分期、不同临界值组均提示Ki-67高表达者预后不良。Ki-67临界值定义在50%是目前的最佳临界值。结论:Ki-67高表达在预测肺腺癌预后方面具有临床意义,未来需要进行更多高质量前瞻性研究来验证完善这一发现。     

ANGPT1基因在肺腺癌组织中的表达及其预后价值分析

目的:探索血管生成素1（angiopoietin 1,ANGPT1)在肺腺癌组织中的表达及预后意义。方法:从癌症基因组图谱(TCGA)数据库收集肺腺癌和肺鳞癌数据,并下载ANGPT1基因表达谱资料及临床信息资料。采用t检验明确ANGPT1在肺癌组织和正常组织中的表达差异,χ2检验分析ANGPT1基因表达与肺腺癌患者临床病理特征的相关性,Log-rank检验进行生存分析;利用基因集富集分析（Gene Set Enrichment Analysis,GSEA）方法,预测肺腺癌中可能受ANGPT1调控的相关通路。结果:ANGPT1基因在肺癌组织中低表达;其表达水平与T分期（P=0.013)呈负相关;ANGPT1低表达的肺腺癌患者预后明显差于高表达患者（P=0.006）,是影响肺腺癌预后的独立保护因素(P＜0.05)。GSEA结果显示,ANGPT1可能通过调节G2M检查点、DNA损伤修复、凋亡、mTOR信号、MYC信号、有丝分裂纺锤体等细胞增殖相关通路影响肺腺癌的发生发展。结论:ANGPT1是肺腺癌的独立预后保护因素,可能成为肺腺癌的潜在预后标志物和治疗靶点。     

Acinic cell adenocarcinoma. A clinicopathologic analysis of 294 cases

Two hundred and ninety-four cases of acinic cell adenocarcinoma were reviewed for the purpose of defining the clinical parameters and determining the distribution of the four histomorphologic tissue patterns and five cell types for correlation to biologic behavior. The vast majority occurred in the parotid gland. There was a male predominance and a peak incidence in the third decade of life. The tumors were usually less than 3 cm in diameter and were slow growing. Pain was a common symptom, but was not indicative of prognosis. Nearly one half of the neoplasms exhibited multiple tissue growth patterns, and three fourths of the tumors displayed more than one cell type. The microcystic pattern was seen most frequently, regardless of the biological behavior of the tumors. The well-differentiated acinic cell was the most prevalent cell type except in cases with metastases, where the intercalated-duct cell type was slightly more frequent. Follow-up of 244 cases revealed a recurrence rate of 12%, a metastatic rate of 7.8%, and death rate of 6.1%. Since all histomorphologic patterns and cell types were manifest in tumors which recurred, metastasized, or caused the death of the patients, it seems appropriate to consider these neoplasms as low-grade adenocarcinomas rather than essentially benign with occasional unpredictable malignant behavior.     

Prognostic value of Goseki histological classification in adenocarcinoma of the cardia

Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1-142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma.     

Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

Lung adenocarcinoma is one of the most frequent causes of malignant pleural effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic changes are commonly related to human neoplasia, scarce date is available on patients with MPE. We aimed to estimate the prognostic value of DNA methylation of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR was used to study the methylation status of the promoter region of tumor suppressor genes p16/INK4a, MGMT, BRCA1 and RARβ in pleural fluid. Clinical data and survival were collected. Survival analysis was performed using Kaplan-Meier plots and Cox regression. Hypermethylation in at least one gene was detected in 25 patients (83.3%). On multivariate analysis factors significantly associated with shorter survival were the lack of hypermethylation in any of the studied genes (hazard ratio = 9.3; p = 0.001), Charlson index ≥ 3 (hazard ratio = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001). Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be useful in predicting prognosis, but further studies are needed to validate our findings.