AgNoRs图像分析与儿童NHL预后的关系

本实验用图像分析技术测定了儿童ＮＨＬ３３例石蜡包埋组织标本的ＡｇＮＯＲｓ参数（数量和面积），探讨了ＡｇＮＯＲｓ参数与临床特征、工作分类及生存的关系。结果显示：１．ＡｇＮＯＲｓ与生存、工作分类及年龄之间差异有统计学意义（Ｐ＜０．０５），ＡｇＮＯＲｓ数量多，面积大，生存时间短，反之结果相反。２．ＡｇＮＯＲｓ的中位数可做为预测患儿预后更客观直接的指标，大于中位数，生存期短，小于中位数，生存期长。因此，ＡｇＮＯＲｓ可成为儿童ＮＨＬ重要的预后指标。     

恶性淋巴瘤AgNORs定量分析的临床意义

采用核仁组成区相关嗜银蛋白（ＡｇＮＯＲｓ）染色技术，对７１例淋巴结良、恶性病变的组织石蜡切片进行ＡｇＮＯＲｓ定量研究。结果显示：３２例淋巴结良性病变平均每个细胞核内ＡｇＮＯＲｓ计数为１．７９±０．５９，３１例恶性淋巴瘤平均每个细胞核内ＡｇＮＯＲｓ计数为６．６２±３．０２，８例淋巴结内低分化转移癌平均每个细胞核内ＡｇＮＯＲｓ计数高达１３．７７±５．２４，表明良、恶性病变ＡｇＮＯＲｓ计数差别十分显著（Ｐ＜０．０１）。２０的非何杰金淋巴瘤（ＮＨＬ）中，低度恶性组ＡｇＮＯＲｓ计数为３．７９±１．４６，而中、高度恶性组ＡｇＮＯＲｓ计数为平均每个细胞核内ＡｇＮＯＲｓ８．２８±２．５８，两组比较差别有显著意义（Ｐ＜０．０１），显示低分化的恶性肿瘤，具有更加恶性的生物学行为。     

乳腺癌核仁组成区与雌激素及孕激素受体的关系

本文采用银胶染色法，雌二醇及孕酮的酶联亲和组化方法，检查了６０例乳腺癌的ＡｇＮＯＲｓ、ＥＲ和ＰＲ。６０例中女性５９例，男性１例。单纯癌２８例，髓样癌１０例，浸润性导管癌１８例，导管癌２例，粘液腺癌２例。经方差分析ＥＲ（＋）与ＥＲ（－）者间，ＰＲ（＋）与ＰＲ（－）者间、ＥＲ（＋）ＰＲ（－）与ＥＲ（－）ＰＲ（－）者间的ＡｇＮＯＲｓ数差异有显著性，Ｐ＜０．０１。以上结果表明ＡｇＮＯＲｓ数是反映细胞增生的指标，并且ＡｇＮＯＲｓ的数量与ＥＲ（＋）、ＰＲ（十）及ＥＲ（＋）ＰＲ（＋）呈负相关性，ＡｇＮＯＲｓ亦可作为乳腺癌预后的估计指标。     

宫颈良、恶性病变核仁组成区蛋白定量与宫颈癌预后的研究

应用核仁组成区蛋白嗜银（ＡｇＮＯＲ）技术，对１０９例宫颈良、恶性病变进行了ＡｇＮＯＲ定量研究。结果表明：１．慢性宜颈炎、宫颈非典型增生、宫颈鳞癌三种病变的ＡｓＮＯＲ均值有显著差异（Ｐ＜０．０１）。２．宫颈鳞癌组织学１级ＡｇＮＯＲ计数低于组织学Ⅱ级（Ｐ＜０．００１）。３．随访１０年以上的７３例宫颈鳞癌患者，核仁组成区蛋白高均值组（≥５）的患者生存时间显著短于低均值组（＜５）（Ｐ＜０．０５），１０年生存率分别为１８％与４６％。作者认为，ＡｇＮＯＲ计数可作为一种新的肿瘤定量指标，在宫颈良、恶性病变的鉴别诊断、选择最佳治疗方案、推测宫颈癌预后等方面具有重要的临床价值。     

AgNORs检测在原发性胆囊癌诊断中的价值

ＡｇＮＯＲｓ检测在原发性胆囊癌诊断中的价值卿德科，夏亮芳核仁组成区相关嗜银蛋白（ＮｕｃｌｅｏｌａｒＯｒｇａｎｉｚｅｒＲｅ－ｇｉｏｎ－ａｓｓｏｃｉａｔｅｄＡｒｇｙｒｏｐｈｉｌＰｒｏｔｅｉｎｓ，简称ＡｇＮＯＲｓ）的检测有助于某些肿瘤的诊断及鉴别诊断［１～...     

AgNOR在淋巴结病变良恶性鉴别诊断中的价值

本文应用核仁组成区银染色（Ａｇ－ｓｔａｉｎｅｄＮｕｃｌｅｏｌａｓＯｓｇａｎｉｓｅｓＲｅｇｉｏｎｓ，ＡｇＮＯＲｓ）技术对２０例组织细胞性坏死性淋巴结炎、１０例非何杰金氏恶性淋巴瘤的石蜡切片标本进行定量研究。结果表明，组织细胞性坏死性淋巴结炎细胞核内ＮＯＲＳ均值为１．４２±０．１０（ｘ±ＳＤ），显著低于非何杰金氏恶性淋巴瘤的ＮＯＲＳ均值（６．０８±１．３６，ｘ±ＳＤ），Ｐ＜０．００１。提示ＡｇＮＯＲｓ的定量研究对组织细胞性坏死性淋巴结炎与非何杰金氏恶性淋巴瘤的鉴别诊断具有一定价值。     

宫颈良,恶性病变核仁组成区蛋白定量与宫颈癌预后的研究

应用核仁组成区蛋白嗜银（ＡｇＮＯＲ）技术，对１０９例宫颈良、恶生病变进行了ＡｇＮＯＲ定量研究。结果表明：１．慢性宫颈炎、宫颈非典型增生、宫颈鳞癌三种病变的ＡｇＮＯＲ均值有显著差异（Ｐ〈０．０１）。２．宫颈鳞癌组织学Ｉ级ＡｇＮＯＲ计数低于组织学Ⅱ级（Ｐ〈０．００１）。３．随访１０年以上的７３例宫颈鳞癌患才，核仁组成区蛋白高均值组（≥５）的患才生存时间显著短于低均值组（〈５）（Ｐ〈０．０５），１０年生     

血卟啉衍生物对鼠肿瘤细胞DNA含量,AgNORs的影响

应用图像分析技术测定大鼠移植Ｗ２５６肿瘤单纯放射治疗组（对照组）和血卟啉衍生物并放射治疗组（实验组）肿瘤细胞的ＤＮＡ含量及ＡｇＮＯＲｓ计数，探讨血卟啉衍生物对恶性肿瘤放射治疗的增敏作用。结果显示实验组大鼠肿瘤细胞ＤＮＡ含量为（５．８４±１．２２）Ｃ，ＡｇＮＯＲｓ计数为２．４２±０．７３；对照组大鼠肿瘤细胞ＤＮＡ含量为（７．８３±０．６８）Ｃ，ＡｇＮＯＲｓ计数为５．３５±０．８４；前者ＤＮＡ含量及ＡｇＮＯＲｓ计数显著低于后者（ｔ＝６．３７，ｔ＝１１．７７，Ｐ＜０．０１）。表明血卟啉衍生物对恶性肿瘤放射治疗有明显的增敏作用     

紫外光血液辐照疗法对放射治疗鼠肿瘤细胞DNA含量、AgNORs计数的影响

应用多功能图像分析仪，检测了鼠Ｗ２５６移植性肿瘤细胞ＤＮＡ含量，并同时测定细胞ＡｇＮＯＲｓ计数，探讨紫外光血液辐照疗法（ＵＢＩ）对放射治疗的增敏作用。结果表明；光量＋放疗组肿瘤细胞ＤＮＡ含量为５．３４±１．０９Ｃ，ＡｇＮＯＲｓ计数为２．２４±０．４３；单纯放疗组肿瘤细胞ＤＮＡ含量为７．８３±０．８６Ｃ，ＡｇＮＯＲｓ计数为５．３５±０．８４；前者ＤＮＡ含量及ＡｇＮＯＲｓ计数显著小于后者（Ｐ＜０．０５）。表明ＵＢＩ对放疗恶性肿瘤有明显的增敏作用。     

卵巢癌实验性化疗增敏中核仁形成区相关嗜银蛋白的图像分析

本实验以人卵巢癌裸鼠皮下移植瘤（ＣＯＣ１／ＤＤＰ）为模型，运用银染和图像分析，观察瘤细胞核仁形成区相关嗜银蛋白（ＡｇＮＯＲｓ）在化疗增敏前后的变化。顺铂用环孢素Ａ增敏后，ＡｇＮＯＲｓ面积，颗粒数及面积与核面积比值均明显低于未增敏组（Ｐ＜０．０５）。提示ＡｇＮＯＲｓ定量研究可作为判断肿瘤化疗疗效，估计预后的一项参考指标。     

Prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas.

The aim of the present research was to evaluate the prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. For this purpose a series of 100 consecutive, previously untreated adults with advanced malignant non-Hodgkin's lymphomas was analyzed. The median age of the patients was 54 years; 61 patients were males. Although the number of the various groups considered was limited, a statistically significant difference (p less than 0.001) was found in the median survival of patients with lymphomas of low-grade malignancy (lymphocytic, lymphoplasmacytoid, centrocytic, centroblastic-centrocytic lymphoma) and lymphomas of high-grade malignancy (centroblastic, lymphoblastic, immunoblastic lymphoma). A difference in survival (p less than 0.001) was also observed among the patients with lymphocytic lymphoma and those with centroblastic-centrocytic lymphoma, whereas no significant difference in survival was found between the histological subtypes of high-grade malignant lymphomas. Our observations support the opinion that the Kiel classification is useful in clinical practice to distinguish the histological types with a better prognosis from those with a worse one; in addition this classification appears to be of conceptual value.     

Bone marrow histopathology and prognosis in malignant lymphomas.

Bone marrow trephine biopsies of patients with non-Hodgkin's malignant lymphomas (ML), followed for at least 4 years, were investigated using univariate and multivariate survival analyses to detect which anagraphic data and histomorphologic medullary patterns before therapy were related to the prognosis. In 234 ML (146 low grade, 88 high grade), univariate analysis showed that survival was reduced by bone marrow involvement, absence of reactive lymphoid nodules, and low marrow cellularity. Moreover, in low-grade ML, patients 50 years or older and showing absence of myeloid hyperplasia, excess of hemosiderin and mast cell hyperplasia had significantly lower-survival rates. The prognostic relevance of these parameters did not change when cases without marrow involvement were separately analyzed. Multivariate analysis showed that, besides marrow involvement, age and myeloid hyperplasia had significant prognostic importance in low-grade ML, and lymphoid nodules in high-grade ML. Our data confirm the value of bone marrow histopathology in ML and indicate that the prognosis is related not only to medullary involvement but also to the morphology of the uninvolved marrow.     

Malignant lymphomas in patients with or at risk for AIDS: a report of 50 cases observed in Italy

For the first time the presence of a consistent number of malignant lymphomas among persons at high risk for AIDS has been documented in Italy. The majority of our cases started to occur in 1983, in line with the trend for a 2-year delay in the spread of the epidemic of AIDS in Europe. The patients with non-Hodgkin's lymphomas had an increased incidence of high grade subtypes, particularly of the Burkitt type, and were in an advanced stage with frequent extranodal involvement. Patients with Hodgkin's disease had a lower incidence of extranodal localization in comparison with the North American series. American patients with malignant lymphomas were reported to be predominantly homosexual; in contrast, the Italian cases were mostly drug addicts. The occurrence of malignant lymphomas was also correlated in Italian patients as well as in American patients with a shorter survival time, when compared with malignant lymphomas occurring in the same age group of the general population.     

Cancer incidence and survival in patients 65 years of age and older

The impact of cancer on persons 65 years of age and older has been assessed by examining incidence rates and survival rates. For all cancers combined, the incidence rate shown in Table 4 for males 65 and older (2,468.2 per 100,000) is four times the age-adjusted rate for males 45 to 64 years of age (586.7). For elderly females, the incidence rate is twice that for females aged 45 to 64 (1,401.1 versus 609.7). Ratios of incidence rates for older versus younger males are about four to five for cancers of the stomach, colon, rectum, pancreas, and urinary bladder, and for leukemia; about three for cancers of the lung and kidney, and for non-Hodgkin's lymphomas; and 10 for cancer of the prostate. For females, the corresponding ratios are similar to those for males, although a little lower for cancers of the colon, rectum, and urinary bladder, and for leukemia, and a little higher for cancers of the stomach and pancreas. The ratios for breast, uterine cervix, uterine corpus, ovary, and lung are less than two. The relative survival rates for patients 65 and older are for many cancer sites only a few percentage points lower than rates for those 45 to 64 years of age (Table 5), suggesting that patients in this age group fare only a little worse than younger patients in escaping the effects of cancer once it has been diagnosed. Exceptions are cancer of the urinary bladder and non-Hodgkin's lymphomas for both men and women and cancers of the uterine cervix, uterine corpus, ovary, and kidney for women. For these sites, the survival rates for older patients are considerably lower than for their younger counterparts. For female breast cancer patients, there was no difference in the five-year relative survival rate for those 65 and older compared with those 45 to 64.     

Different age limits for elderly patients with indolent and aggressive non-hodgkin lymphoma and the role of relative survival with increasing age

BACKGROUND: There is no consistent definition at what age patients with non-Hodgkin lymphoma (NHL) are considered "elderly." This might hamper well balanced decisions with respect to treatment. METHODS: From a population-based NHL registry the age groups younger than 60 years, 60-64 years, 65-69 years, 70-74 years, and 75 years and older were analyzed in relation to the revised European-American lymphoma classification and to the age-adjusted International Prognostic Index (IPI). The prognostic value of the variables from the age-adjusted IPI was determined. The relative survival probabilities were calculated. RESULTS: The incidence of diffuse large B-cell lymphoma (DLBL) increased with advancing age, as was the case for small lymphocytic lymphomas. Follicular lymphomas were less frequently encountered with advancing age. With respect to the so-called indolent lymphomas, a decreasing complete remission rate and overall survival rate (5-year) was observed for patients older than 70 years, whereas patients with DLBL fared worse when older than 65 years and 60 years, respectively. The age-adjusted IPI score was discriminative for prognosis. However, even with an IPI score nil, the age group older than 75 years fared significantly worse (P < 0.009), but less so with the relative survival model. The relative survival at 5 years was 60%, 53%, 48%, 35%, and 32% for the 5 respective age groups. CONCLUSIONS: Patients with indolent lymphomas become elderly when they are older than 70 years, but when aggressive lymphoma is concerned this occurs when patients are older than 65 years. For patients with an IPI score nil, age older than 75 years is the dominant prognostic factor. The negative influence of concomitant disease on overall survival, although continuously increasing in older age groups, seems to diminish for patients older than 75 years when compared with the general Dutch population.     

Mitotic activity in non-Hodgkin's lymphoma. Relation to the Kiel classification and to prognosis

At histopathological diagnosis of non-Hodgkin's lymphoma (NHL) the mean number of mitoses in 10 high power fields (X 40) was determined in thin sections (2 micron) and designated 'mitotic index' (MI). In 38 patients the thymidine labelling index (LI) of the lymphoma cells was also determined. There was a close correlation between MIs and LIs (r = 0.81, P less than 0.001) indicating that MI reflects the proliferative activity in NHL. Among 101 patients with NHL classified according to the Kiel nomenclature MIs were generally lower in lymphomas of low grade malignant type than in the high grade malignant lymphomas. The variation of MIs within morphological subgroups was especially pronounced in high grade lymphomas. Only 18 of 49 patients (37%) with MI greater than or equal to 2 have survived for 2 years in contrast to 37 of 52 patients (77%) with MI less than 2 (P = 0.001). For patients with histologically low grade lymphomas and MI greater than or equal to 2.0 the median survival was 23 months and for those with MI less than 2.0 58 months (P = 0.09). Patients with high grade lymphomas and MI greater than or equal to 2.0 had a median survival of 15 months compared to 57 months for those with MI less than 2.0 (P = 0.04). In a multivariate analysis of 50 patients with centroblastic-centrocytic (CB-CC) or centroblastic (CB) lymphomas the importance of different prognostic factors was analysed. Among the variables age, MI, growth pattern (follicular vs. diffuse), cell type (CB-CC vs. CB), clinical stage (I vs. II-IV), initial chemotherapy (active vs. less active) only age and MI gave significant prognostic information. It is concluded that the assessment of mitoses in NHL gives prognostic information in addition to histopathologic classification. The method is simple and the proliferative activity and histopathological diagnosis can be ascertained routinely on the same occasion.     

Primary splenic presentation of malignant lymphoma and related disorders. A study of 49 cases

The diagnosis of malignant lymphoma presenting as an initial splenic manifestation may go unrecognized as such when peripheral lymph nodes are not enlarged and when results of bone marrow biopsies are negative. Tissues from 49 patients, ranging in age from 15 to 78 years, in whom the original diagnosis of malignant lymphoma and related conditions was made at splenectomy, were classified as: diffuse small lymphocytic (20), diffuse large cell (11), diffuse small cleaved (5), diffuse large cell, immunoblastic (5), follicular small cleaved cell (3), and follicular mixed small cell and large cell (2). Two additional spleens, diagnosed as acute blastic leukemia, were initially confused with malignant non-Hodgkin's lymphoma by light microscopy. One patient presented with Hodgkin's disease confined to the spleen. For the non-Hodgkin's lymphoma group, parameters of age, sex, splenic weight (range, 226-4000 g), lymph node, bone marrow, or liver involvement did not adversely influence prognosis. Abdominal lymph nodes were positive in 31 of 37 patients having splenic hilar and/or abdominal lymph nodes available for review. Of 29 patients with adequate follow-up, 7 died of disease, 5 were free of disease at 3 years, 2 were free of disease at 5 years, 2 were alive with disease at 3 years, 4 were alive with disease at 5 years, and 9 died from second malignancies, unknown, or unrelated causes. Six of the 7 patients who died of lymphoma were classified as large cell (four diffuse large cell and two diffuse large cell, immunoblastic), with a mean 2-year survival. One patient died of leukemia. Those lymphomas classified as low grade behaved in an indolent fashion. The morphologic diversity of these cases emphasizes the need for the initial recognition and correct classification of lymphomas which present in the spleen, since survival is best determined according to histologic type.     

Protein expression of cell cycle regulator, p27Kip1, correlates with histopathological grade of non-Hodgkin's lymphoma.

The protein p27Kip1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas (P<0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.     

Protein Expression of Cell Cycle Regulator, p27Kip1, Correlates with Histopathological Grade of Non-Hodgkin's Lymphoma

The protein p27^Kp1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas ( P <0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.