Immunoglobulin and Myc gene structure in lymphnode biopsies from HIV-positive patients with LAS and lymphoma

The pattern of immunoglobulin (Ig) gene rearrangement and the genomic structure of the Myc locus were investigated in the DNA of 20 lymphnode biopsies of patients suffering from lymphoadenopathy-associated syndrome (LAS) and from 3 patients with Burkitt's lymphoma. Although polyclonality was the prevalent pattern of Ig gene rearrangement observed in LAS, in 30% of the cases discrete bands of Ig heavy chain gene rearrangement were identifiable due to the presence of monoclonal or oligoclonal cell populations. However, structural alterations of the Myc gene were not detected in any cases. As expected, in all three Burkitt's lymphomas studied, the lymphnode DNA displayed a clonal pattern of Ig heavy chain gene rearrangement. The Myc was altered in two cases, which presented a truncation of the gene beginning within a very short region of the first intron. By contrast, the breakpoint positions on chromosome 14 mapped in different regions of the Ig loci, which in both cases involved the switch (SH) area. Data confirm the relatively common occurrence of oligoclonal expansions within B cells in LAS and the frequent involvement of the Myc oncogene in the process of lymphomagenesis in individuals positive for human immunodeficiency virus (HIV).     

Role of liquid biopsies in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer worldwide, with a global incidence of over 1 million cases. In the era of personalized medicine, tumor sampling is essential for characterizing the molecular profile of individual tumors. This provides pivotal information regarding optimal sequencing of therapy and emergence of drug resistance, allowing for timely therapy adjustment. However, tumor tissue sampling offers static information in a single time point and area of disease at the time of biopsy, which may not entirely represent the heterogeneity of molecular alterations. Moreover, tumor biopsies often involve invasive procedures with potential risks to patients. Less invasive, safer, and real-time methods such as liquid biopsies have generated increasing interest as a surrogate of solid tumor biopsies. Liquid biopsy allows for noninvasive survey with detection of cell-free circulating tumor DNA (ctDNA) or circulating tumor cells. Blood-based assays are the most widely studied. Additionally, the quantity of ctDNA detected has been shown to correlate with tumor burden and enables assessment of tumor heterogeneity. In this article, we discuss the concept of liquid biopsies including ctDNA and circulating tumor cell, and their current application in the diagnosis and management of CRC. We suggest that liquid biopsies can be successfully used to characterize the molecular profile of CRC, monitor disease, detect minimal residual disease after surgery, and identify therapeutic targets and mechanisms of drug resistance. This strategy could potentially imply an early change in treatment, sparing unnecessary side effects, and minimizing health costs. Combined radiological and liquid biopsy assessments will likely become more standard in CRC oncology. However, large prospective studies are needed to definitively establish the role of liquid biopsy.     

Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

Background  

Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown.     

Primary CD56 positive lymphomas of the gastrointestinal tract

BACKGROUND: Primary CD56 positive lymphoma of the gastrointestinal (GI) tract is rare. Genotypically, these tumors can be classified into natural killer (NK)-like T-cell lymphoma or NK cell lymphoma by the presence or absence of T-cell receptor (TCR) gene rearrangement. However, they have a considerable degree of morphologic and immunophenotypic overlap, making a definitive diagnosis difficult. METHODS: The clinicopathologic features of three patients with primary CD56 positive lymphoma of the small and large bowel are presented. This is followed by a review of the English literature from 1966 to the present. RESULTS: All patients had CD56 positive/CD3epsilon positive disease on paraffin section. Two patients were positive for Epstein-Barr virus-encoded early nuclear RNAs (EBER) according to in situ histochemistry results and were negative for TCR gene rearrangement, consistent with primary NK lymphoma of the GI tract. The other patient was EBER negative with rearranged TCR, consistent with NK-like T-cell lymphoma. There was no clinical or histologic evidence of enteropathy in any of the patients. The major presenting symptoms included fever, weight loss, and intestinal perforation. All patients died between 1 week and 6 months after diagnosis despite undergoing surgery and intensive chemotherapy. CONCLUSIONS: These results, together with a literature review, suggest that primary NK cell lymphoma of the GI tract may be considered a distinct clinicopathologic entity. Both primary NK and NK-like T-cell lymphoma pursue an aggressive clinical course. EBER and TCR gene rearrangement are useful in distinguishing NK cell lymphoma from NK-like T-cell lymphoma, particularly when frozen tissue is not available for immunophenotyping.     

Role of diagnostic imaging in abdominal lymphadenopathy

Abdominal lymph node chains and route of lymph drainage of various organs (stomach, duodenum, liver, gallbladder, pancreas, small intestine, appendix, blind intestine, colon rectum) are analyzed according to their location. The role of conventional radiology and diagnostic imaging is evaluated in the study of abdominal lymphatic system with particular reference to lymphangiography and the new procedures of sonography, CT and MRI. Present methods used in inflammatory abdominal lymphadenopathy with special attention to tuberculous lymphadenitis, liver cirrhosis, neoplastic abdominal lymphadenopathy, colorectal and pancreatic cancer, are illustrated. Combined modality imaging is considered in gastric cancer based on the evolution of the classification of gastric lymph nodes. The role of sonography, endoscopic ultrasonography, spiral CT and MRI is assessed in gastric cancer N staging. A retrospective study is analyzed and perspectives for the application of a new CT protocol are proposed. PET potentialities in the study of abdominal lymph nodes are examined.     

Utility of the percentage of positive prostate biopsies in predicting PSA outcome after radiotherapy for patients with clinically localized prostate cancer

PURPOSE: To determine the utility of the percentage of positive prostate biopsies (PPPB) in predicting prostate-specific antigen (PSA) outcome after external beam radiotherapy alone. METHODS AND MATERIALS: The records of 750 clinical Stage T1 and T2 patients treated by external beam radiotherapy alone with a median follow-up of 80 months were reviewed. Of the 750 patients, 345 were eligible for analysis; 255 (74%) had undergone sextant biopsies, 28 (8%) <6 biopsies, and 62 (18%) >6 biopsies. The pretreatment PSA level (<10, 10-20, >20 ng/mL), biopsy Gleason score (2-6, 7, 8-10), and clinical stage (T1-T2a, T2b, T2c), uni- or bilateral positive biopsy, radiation dose, and PPPB were analyzed as potential predictors of PSA outcome. The PPPB data were analyzed as a continuous and as a categorical variable. RESULTS: PPPB was a significant predictor of the time to PSA failure on univariate analysis as a continuous (p = 0.0053) and as a categorical (<50% vs. >or=50%, p = 0.0077) variable. In multivariate analysis, a trend was noted for worse 5-year PSA failure-free survival based on PPPB >or=50% vs. <50% (p = 0.082). Sixty-four patients experienced biochemical failure according to the American Society for Therapeutic Radiology Oncology definition. The 5-year PSA failure-free survival rate was 79% vs. 69% (p = 0.02) and the clinical disease-free survival rate was 97% vs. 86% (p = 0.0004) for patients with <50% vs. >or=50% PPPB. PPPB was not a significant predictor for the time to PSA failure within the traditional risk groups (low, intermediate, and high) on multivariate analysis. CONCLUSION: PPPB was a predictor of post-external beam radiotherapy PSA outcome in clinically localized prostate cancer; but in this cohort it did not provide additional information beyond the traditional risk stratification schema.     

The expression pattern of CD56 (N-CAM) in human bone marrow biopsies infiltrated by acute leukemia

In hematological neoplasms CD56 (N-CAM) is expressed by T/natural killer (NK) cell lymphoma, by most neoplastic plasma cells in multiple myeloma and also in a subset of acute myelogenous leukemias (AML). In the latter, it is an indicator of poor clinical outcome. Most of the data on CD56 expression in acute leukemia have been obtained by flow cytometric analysis. Up to now, no systematic analysis of the expression pattern of CD56 in formalin fixed paraffin embedded bone marrow biopsies of acute leukemias has been performed. We immunohistochemically studied the expression of CD56 in a series of 141 bone marrow biopsies fixed in Sublimat Mercury II Chloride (SUSA) including 100 cases of AML FAB M0-M7, 11 cases of AML not further specified, 3 cases of biphenotypical leukemia, 20 cases of acute lymphoblastic leukemia (ALL) and 7 cases of reactive bone marrow biopsies. Overall, 14 of 134 (10%) leukemia cases were positive for CD56. Detail analysis revealed positivity in 5/13 cases of AML M5 (38%), 3/9 AML M1 (33%), 1/8 AML M0 (13%), 1/11 AML not specified (9%), 2/31 AML M2 (7%) and 2/26 AML M4 (8%). All cases of ALL and biphenotypic leukemias were CD56 negative. The CD56 expression in AML M5 was statistically significant (p=0.003). On paraffin embedded bone marrow biopsies CD56 expression occurs in de novo AML with an overall frequency of 13%. It is significantly correlated with AML M5, which is positive in 38% of the cases. Cases of ALL are consistently CD56 negative.     

CD56在小细胞癌组织中的表达及其对诊断的作用

背景与目的:小细胞癌(smallcellcarcinoma,SCC)是恶性度及死亡率高的少见恶性肿瘤,临床病理目前常用神经特异性烯醇化酶(neuron-specificenolase,NSE),触突素(synaptophysin,SYN),嗜铬蛋白(chromograninA,CgA)标记协助诊断,本项目拟研究CD56在小细胞癌组织中的表达并探讨把CD56作为临床病理诊断小细胞癌的标记分子的可能性。方法:收集小细胞癌病例标本共80例,包括肺原发病例42例,其中伴淋巴结转移20例;食管原发病例21例,结直肠原发病例17例。另外随机选取肺非小细胞癌38例作为对照(肺鳞癌26例,肺腺111癌12例),其中淋巴结转移28例。所有标本用CD56,NSE,Syn,CgA,CK和EMA进行免疫组化染色。结果:CD56在肺小细胞癌肿瘤组织及其淋巴结转移灶组织中阳性率显著高于在肺非小细胞癌中阳性率,其在肺小细胞癌原发灶阳性率为90.5%(38/42),转移灶为90.0%(18/20),其在肺非小细胞癌原发灶阳性率为7.8%(3/38),转移灶为3.5%(1/28)(H=85.731,P<0.001),它在小细胞癌肿瘤组织中阳性率明显高于NSE,CgA,CK与EMA的阳性率,其阳性率分别为:CD5686.3%(69/80),Syn78.8%(63/80),CgA73.8%(59/80),EMA66.3%(53/80),CK61.3%(49/80),NSE56.3%(45/80)(H=38.871,P<0.001)。CD56在肺、食管及结直肠小细胞癌中阳性率比较无显著差异,其阳性率分别为肺90.5%(38/42),食管81.0%(17/21),结直肠82.4%(14/17)(H=1.651,P=0.438)。结论:CD56在小细胞癌组织中无论是原发灶还是淋巴结转移灶的阳性率均高,且无器官特异性;CD56可作为临床病理诊断小细胞癌的阳性标记物。     

Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer.

PURPOSE: To determine the clinical utility of the percentage of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for men with PSA-detected or clinically palpable prostate cancer. METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men while accounting for the previously established risk groups that are defined according to pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage. The findings were then tested using an independent surgical database that included data for 823 men. RESULTS: Controlling for the known prognostic factors, the percentage of positive prostate biopsies added clinically significant information (P <.0001) regarding time to PSA failure after RP. Specifically, 80% of the patients in the intermediate-risk group (1992 AJCC T2b, or biopsy Gleason 7 or PSA > 10 ng/mL and 相似文献   

前哨淋巴结活检在早期乳腺癌中的应用价值

目的：探讨活性染料亚甲蓝检测早期乳腺癌前哨淋巴结的可行性及其临床意义。方法：利用亚甲蓝对48例乳腺癌患者进行前哨淋巴结活检（SLNB）并同时行腋窝淋巴结清扫（ALND）,根据病理结果进行评价。结果：SLN检出率为95．8％,SLN对ALN状况预测的敏感度为90．3％,准确率为95．7％,假阴性为6．5％,假阳性为0。结论：前哨淋巴结活检能比较准确地反映早期乳腺癌的腋窝淋巴结转移情况,可为SLN阴性的患者“保腋窝”提供依据。     

Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer

PURPOSE: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. RESULTS: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of < or =50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p = 0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p <0.0001) and overall survival (87% vs. 40%, p = 0.02) by incorporating the percentage of positive prostate biopsy information into a previously established risk stratification system. CONCLUSION: The clinically relevant stratification of PCSS using the percentage of positive prostate biopsies in intermediate-risk patients confirms previous findings based on prostate-specific antigen outcome. These data provide evidence to support the ability to stratify newly diagnosed patients with clinically localized disease into a minimal-risk (low-risk + low biopsy volume [< or =50%] intermediate-risk) or high-risk (high biopsy volume [>50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings.     

Aspects of parasternal lymphnode dissection in radical mastectomy for breast cancer

In order to clarify the surgical aspects for parasternal lymphnode dissection to improve prognosis in patients with breast cancer, we have retrospectively investigated a total of 319 patients with breast cancer who underwent radical mastectomy with parasternal lymphnode dissection. During the 13 years from 1974 to 1986, 418 patients with breast cancer underwent radical mastectomy. Of these, 319 underwent combined dissection of the parasternal lymphnodes. Among these 319 cases, 36 (11.3%) showed pathologically-confirmed positive lymphnode metastasis. In those cases involving a tumor of diameter greater than 5 cm and more than 4 positive metastatic axillar lymphnodes, then the positive parasternal lymphnode metastasis was higher than 30%. The 5-year survival rate was 88.9% for negative parasternal lymphnode metastasis and 44.7% for positive cases (p less than 0.01 logrank test). The standard adjuvant chemotherapy, chemo-endocrine therapy and radiation therapy, each did not significantly affect or improve prognosis. We conclude that parasternal lymphnode positivity is an important factor in radical mastectomy affecting prognosis and a more powerful adjuvant chemotherapy must be developed to improve prognosis.