Miscellaneous primary tumors and metastatic tumors of the uterine cervix

Apart from squamous cell carcinomas and adenocarcinomas (and their precursors), a variety of less common neoplasms, both benign and malignant, arise or initially present within the uterine cervix. This review considers the clinical and pathological features and differential diagnosis of these tumors, which include cervical small cell (neuroendocrine) carcinomas, sarcomas and mixed mullerian tumors, lymphomas and leukemias, germ cell tumors, malignant melanomas, trophoblastic tumors, and metastatic carcinomas. Benign tumors of the cervix are also briefly discussed.     

Mutational analysis of DNMT3A gene in acute leukemias and common solid cancers

DNMT3A, a DNA methyltransferase that functions for de novo methylation, is important in development and many cellular processes related to tumorigenesis. Somatic mutations of DNMT3A gene, including recurrent mutations in its Arg‐882, were recently reported in acute myelogenous leukemia (AML), strongly suggesting its role in development of AML. To see whether DNMT3A mutation occurs in other malignancies as well, we analyzed DNMT3A in 916 cancer tissues from 401 hematologic malignancies (AML, acute lymphoblastic leukemias (ALL), multiple myelomas and lymphomas) and 515 carcinomas (lung, breast, prostate, colorectal and gastric carcinomas) using a single‐strand conformation polymorphism (SSCP) assay. We identified DNMT3A mutations, especially the Arg‐882 mutations, in adulthood AML (9.4%). In addition, we found DNMT3A mutations in pre‐B‐ALL and three lung cancers at lower frequencies. Allelic loss of DNMT3A was frequently observed in most cancer types analyzed, including lymphomas (48.1%), gastric cancers (23.5%) and lung cancers (18.3%) irrespective of DNMT3A mutation. Also, loss of DNMT3A expression was common in lung cancers (46.4%), and was associated with the allelic loss. Our data indicate that DNMT3A gene is mutated mainly in AML, but it occurs in other cancers, such as ALL and lung cancer, despite the lower incidences. Also, the data suggest that DNMT3A is altered in many cancer types by various ways, including somatic mutations, allelic loss and loss of expression that might play roles in tumorigenesis.     

Pax5 expression in non-Hodgkin's lymphomas and acute leukemias

The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffin embedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias.     

An image cytometric DNA-analysis in breast neoplasms. Parameters of DNA-aneuploidy and their relationship with conventional prognostic factors.

In this prospective study, an image cytometric DNA-analysis was performed in 86 women with breast neoplasms (72 primary invasive carcinomas and 14 benign lesions). Four DNA ploidy parameters were analysed: histogram type (according to AUER classification), DNA-index, tumor cells with DNA content above the 5n limit and DNA malignancy grade (DNA-MG, calculation according to B?cking). Their correlations with well established prognostic factors in breast carcinomas (tumor size, lymph node status, histologic grade, hormone receptor content) were studied. All but one benign lesions were diploid (13/14 cases), whereas the majority of the primary invasive breast carcinomas were aneuploid (58/72 cases). A predominance of carcinomas with a percentage of cells superior or equal to 1% with DNA content above the 5n limit was observed (54 cases out of 58). Most of the aneuploid tumors had a histogram type III or IV (53 cases) or a high DNA-index (50 cases). Of these 58 aneuploid cases, only 26 tumors had a DNA-MG superior to 1. Interestingly, 26 tumors had the 4 criteria of aneuploidy, 19 had 3 and 9 had 2 and only 4 tumors had one parameter. The DNA-MG was significantly related to hormonal receptors (p less than 0.001) and tumor size (p less than 0.01). The histogram types (Auer classification) and the DNA content above the 5n limit were correlated with histologic grade (SBR or SBRM) (p less than 0.02). Concerning the DNA-index no correlation was observed with well established prognostic factors. On the other hand no significant correlation was found between these new biologic variables and lymph node status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumors of the heart

Two thirds of primary tumors of the heart are benign, and half of the benign tumors are myxomas. Metastatic tumors of the heart are 20 to 40 times more common than primary tumors. Metastatic tumors originate mainly in melanomas, leukemias/lymphomas, and carcinomas, especially of the lung or breast. The parts of the heart affected, in decreasing order of frequency, are the pericardium, myocardium, and endocardium. The clinical diagnosis is suggested by a patient with cancer and a normal heart who develops any kind of heart disease that is progressive and unresponsive to the usual methods of treatment. Irradiation, percardiocentesis, and injection with chemotherapeutic agents are effective in ameliorating symptoms from lymphomas/leukemias of the heart and in pericardial effusions due to malignant disease.     

DNA-ploidy and survival in gastric carcinomas: a flow-cytometric study

Summary In 125 gastric carcinomas the nuclear DNA content was determined by flow cytometry from formalin-fixed and paraffin-embedded tissue of surgical specimens. The carcinomas were of intestinal or mixed type (85), and diffuse type (40). DNA-aneuploidy was found in 46% of the intestinal type and in 42% of the mixed type, but only in 15% of the diffuse-type carcinomas (P<0.01). The total rate of DNA-aneuploidy was 34%. Carcinomas localized in the cardia were more frequently DNA-aneuploid than tumours in other localizations (P<0.01). DNA-aneuploid carcinomas had metastasized more frequently to regional lymph nodes (P<0.05) whereas no correlations with tumour stage and cytological/histological grade were detected. In 94 patients follow-up data were available. DNA-aneuploidy was associated with a statistically significant poorer prognosis when compared to DNA-diploid tumours only in advanced gastric carcinomas with lymph node metastases (P=0.0488) and in the subgroup of advanced intestinal and mixed-type tumours (P=0.0289).     

p73基因在卵巢上皮性肿瘤中的表达及甲基化研究

目的 探讨卵巢上皮性肿瘤中p73蛋白的表达和基因启动子的甲基化情况,并观察其与临床病理学特征的关系.方法 制备包括68例卵巢癌、37例卵巢交界性肿瘤和21例卵巢良性肿瘤的组织芯片,用免疫组织化学EnVision法检测上述组织中p73蛋白表达情况,用亚硫酸氧盐修饰后测序法检测13例新鲜卵巢癌组织及5例新鲜卵巢交界性肿瘤组织的p73基因启动子甲基化情况.结果 92.6％ (63/68)的卵巢癌表达p73,p73蛋白总体表达率均值为32％(p73表达率指p73阳性细胞数所占的百分比),其中浆液性癌( 26/26)的表达率均值为40％,高于其他组织类型的癌(P=0.006).按照卵巢癌发病模式区分,Ⅱ型卵巢癌p73表达率均值(40％)高于Ⅰ型卵巢癌(24％),P=0.010.卵巢癌中p73的表达与临床分期及组织学分级无相关性(均P＞0.05).卵巢交界性肿瘤组(30/37)和良性肿瘤组(12/21)p73的总体表达率均值分别为16％和15％,该两组肿瘤中浆液性肿瘤表达率均值均高于黏液性肿瘤(P-0.003,P=0.026).卵巢癌组的p73阳性表达率均值明显高于交界性肿瘤组和良性肿瘤组(均P ＜0.05),交界性肿瘤组与良性肿瘤组比较差异无统计学意义(P＞0.05).浆液性肿瘤( 49/53)中,卵巢癌组(26/26) p73阳性表达率均值明显高于交界性肿瘤组(12/14)和良性肿瘤组(11/13;P =0.024和P=0.002),而卵巢交界性肿瘤组和良性肿瘤组比较差异无统计学意义(P=0.428).黏液性肿瘤(15/27)中,卵巢癌组(6/7)p73阳性表达率均值高于良性肿瘤组( 1/8;p=0.032),而卵巢癌组与卵巢交界性肿瘤组(8/12)、交界性肿瘤组与良性肿瘤组比较,差异均无统计学意义(P=0.234和P=0.201).p73启动子的甲基化结果显示,13例卵巢癌有8例发生甲基化,但每例样本甲基化频率有所不同,总体甲基化频率均值为8.0％.5例交界性肿瘤有2例发生甲基化,总体甲基化频率均值为9.0％,两组比较差异无统计学意义(P＞0.05).卵巢癌组p73甲基化额率与组织类型、发病模式、组织学分级及临床分期均无相关性(均P＞0.05).结论 卵巢上皮性肿瘤多数表达p73,卵巢癌p73的表达率均值明显高于交界性肿瘤和良性肿瘤,浆液性肿瘤高于其他组织类型;p73蛋白表达率与p73基因甲基化程度不存在简单线性相关关系.     

Interaction between transforming growth factor-alpha and c-Ha-ras p21 in progression of human gastric carcinoma

The expression of TGF alpha and c-Ha-ras p21 was studied immunohistochemically in a total of 174 gastric carcinomas, comprising 27 early carcinomas and 147 advanced carcinomas. TGF alpha-immunoreactivity was detected in 7 (25.9%) of the 27 early carcinomas and in 110 (74.8%) of the 147 advanced carcinomas, the incidence being significantly different between the two (P less than 0.01). Out of the 67 c-Ha-ras p21 positive carcinomas, 59 (88.1%) showed TGF alpha-immunoreactivity synchronously. A significant positive correlation was observed between the grade of TGF alpha and incidence of c-Ha-ras p21-immunoreactivity in tumor cells (P less than 0.01). Furthermore, a good correlation was demonstrated between synchronous expression of TGF alpha and c-Ha-ras p21 and depth of tumor invasion (P less than 0.01). The incidence of synchronous expression of TGF alpha and c-Ha-ras p21 in metastatic tumors was significantly higher than that in primary tumors showing no lymphatic metastasis (P less than 0.01). Patients with carcinomas showing synchronous expression of TGF alpha and c-Ha-ras p21 had an extremely poorer prognosis than those without TGF alpha and c-Ha-ras p21. These results indicate that the synchronous expression of TGF alpha and c-Ha-ras p21 plays an important role in high malignancy of gastric carcinomas.     

Assessment of proliferative activity in leukaemic bone marrow using the monoclonal antibody Ki-67.

AIMS--To investigate proliferative activity in leukaemic and lymphomatous bone marrow infiltrates and to assess the feasibility of transport of specimens among institutions. METHODS--Proliferative activity in bone marrow trephine cryosections from 99 patients with non-Hodgkin''s lymphoma (NHL), 23 patients with acute myeloid leukaemia (AML), 11 with acute lymphoblastic leukaemia (ALL), and two with acute undifferentiated leukaemia (AUL) was investigated. Infiltration was seen in 52 out of 99 cases of NHL on bone marrow cryosections. A score was devised to assess pathological infiltrates in bone marrow trephine cryosections using the monoclonal antibody Ki-67. This method of scoring gave a measure of non-erythroid proliferative activity. RESULTS--Mean Ki-67 positivity in bone marrow infiltrates in 31 low grade B cell lymphomas (Kiel classification) was 0.3% before and 4.7% after treatment, 16.4% in seven high grade B cell lymphomas, and 17.8% in 12 peripheral T cell lymphomas. In 48 cases of NHL, bone marrow cryosections had not been infiltrated, and in all but one case the percentage of Ki-67 positive cells in normal marrow was less than 3%; the remaining case showed coexistent myelodysplasia and 8% bone marrow Ki-67 positivity. In eight cases of common ALL at diagnosis, the mean Ki-67 positivity in marrow cryosections was 24.9%, significantly higher than the 2.4% Ki-67 positivity seen in AML (p < 0.05). One of the two cases of common ALL with less than 1% Ki-67 positivity was refractory to treatment. CONCLUSIONS--Proliferative activity of erythroid elements in the bone marrow varies greatly. Immunostaining of bone marrow cryosections using Ki-67 permits accurate assessment of non-erythroid proliferative activity in lymphomas and leukaemia. High grade B cell lymphomas and peripheral T cell lymphomas invading the marrow have very similar mean proliferative activities. Such levels of proliferation are of the same order as those seen in common ALL, but much higher than those seen in AML.     

Estimating loss of the wild-type p53 gene by in situ hybridization of fine-needle aspirates from breast carcinomas.

TP53 mutations have been found in 16-64% of breast carcinomas. The aim of our study was to investigate loss of the wild-type TP53 gene by in situ hybridization (ISH) of fine-needle aspirates (FNAC) from breast carcinomas. The material consisted of FNAC from 33 breast carcinomas, with histologic specimens from 19 of the cases. Routine diagnostic smears were used for cytologic grading. ISH of the wild-type TP53 gene and chromosome 17 was performed on air-dried smears. Hybridization signals were counted in at least 100 nuclei, and the percentage for each signal number was calculated. FNAC from four fibroadenomas as well as cell preparations from five lymphocyte cultures were used as normal/benign controls. Cutoff for defining loss of p53 gene signals was set at 20% of cells with zero and one gene signal only. Concomitant p53 protein expression was determined on 20 histologic sections and eight additionally available air-dried smears. Loss of wild-type p53 gene was found in 20 carcinomas (60.6%). The rate of signal loss varied from 0.4% to 75.3% of the cells. All tumors with aneusomy of chromosome 17 revealed loss of p53 gene signals, as did 42% of the disome cases. Loss of wild-type p53 gene was present in 10 of 16 grade 1 cancers (62.5%), eight of 13 grade 2 tumors (61.5%), and two of four grade 3 cases. Signal loss did not correlate with p53 protein expression. In conclusion, subpopulations with loss of the wild-type p53 gene are a common finding in breast carcinomas; they are detected in more than 60% of the tumors, including grade 1 cancers.     

Electron microscopic studies on the occurrence of activated neutrophils in peripheral blood of children with acute leukemias

Peripheral blood (PB) cells are examined to assess cellular maturity and the degree of bone marrow abnormality in children with acute leukemias. During the ultrastructural assessments of PB cells in these children, we noted a frequent occurrence of activated neutrophils. This phenomenon had not been reported previously. We here report for the first time the identification of activated neutrophils in PB of children with acute leukemias. To examine the impact of activated neutrophils, we compared two groups of children including 18 with acute lymphoblastic leukemia (ALL) and 7 with acute myelogenous leukemia (AML) by an ultrastructural leukocyte count method. Many cases (50%) showed more than 30% activated neutrophils per total neutrophil count in PB. Activated neutrophils were elongated or amoeboid-shaped cells ranging from 13-18 microns in greater diameter with a decreased number of granules in the cytoplasm. A significantly higher rate of activated neutrophils was observed in ALL as compared with AML (median: 42.97% vs. 10.64%). Non-leukemic hospitalized (n =3) and healthy (n = 3) control cases showed a median rate of 3.32% activated neutrophils in PB. These findings reveal that a significantly high rate of activated neutrophils occurs in PB of children with ALL which may be exploited in the diagnostic assessment of children with acute leukemias.     

Low incidence of TEL/AML1 fusion and TEL deletion in Korean childhood acute leukemia by extra-signal fluorescence in situ hybridization

TEL/AML1 fusion in acute leukemia results from cryptic translocation of chromosome 12 and 21, the presence of which suggests a favorable prognosis. The incidence of TEL/AML1 fusion in B-lineage ALL is approximately 25%, but the incidence in Korea has not yet been reported. To investigate the incidence of TEL/AML1 fusion and TEL deletion, bone marrow specimens from 77 Korean children with newly diagnosed acute leukemia were analyzed by FISH. We applied extra-signal FISH to discriminate a true TEL/AML1 fusion from a false-positive fusion signal. To determine the cut-off value of the TEL/AML1 fusion signal, 20 normal bone marrow specimens and 28 normal peripheral blood specimens were also analyzed. The frequency of patients with TEL/AML1 fusion was 13.3% (4 cases) among 30 B-lineage ALL and 9.5% among 42 ALL. One TEL/AML1 fusion-positive patient was also found among 4 acute biphenotypic leukemias. TEL/AML1 fusion was not found in any samples from patients with T-lineage ALL or AML. The incidence of TEL deletion was 6.7% (2 cases) among 30 B-lineage ALL and 4.8% among 42 ALL. The incidences of TEL/AML1 fusion and TEL deletion in Korean children with acute leukemia appear to be lower than those in other countries, suggesting a racial difference.     

Histologic grading of noninvasive papillary urothelial tumors: validation of the 1998 WHO/ISUP system by immunophenotyping and follow-up

Cytokeratin (CK) 20, Ki-67, and p53 were applied to 84 noninvasive papillary urothelial tumors graded by the 1973 World Health Organization (WHO) and 1998 WHO/International Society of Urological Pathology (ISUP) systems. In the WHO/ISUP classification, all benign lesions showed normal CK20 staining and all carcinomas showed abnormal staining. The Ki-67 index was significantly different between benign and malignant lesions (P < .05) and between low- and high-grade carcinomas (P < .001). p53 was negative in all benign lesions, with a significant difference between low- and high-grade carcinomas (P < .001). Tumor recurrence was significantly different between low- and high-grade carcinomas (no recurrences among the papillary urothelial neoplasms of low malignant potential). By the 1973 WHO classification, normal CK20 staining was present both in benign lesions and in carcinomas. Ki-67 staining did not distinguish between grade 2 and grade 3 carcinomas (P > .05), and there was no difference in p53 staining in grades 1 and 2 carcinomas (P > .05). Recurrences were not different between grades 1, 2, and 3 carcinomas. All biologic markers studied and tumor recurrences were significantly different among papillary lesions classified by the WHO/ISUP system but not by the 1973 WHO system, validating the predictive value of the WHO/ISUP system and providing objective markers for the grading of papillary urothelial tumors.     

Quantitative acute leukemia cytogenetics.

Using literature data on cytogenetic abnormalities in 3,612 cases of acute myeloid leukemia (AML) and 1,551-cases of acute lymphocytic leukemia (ALL), we have attempted to quantify the information value of finding the typical ALL- and AML-associated chromosome aberrations. Sensitivity, specificity, and predictive value of finding or not finding a given aberration were calculated for several diagnostic scenarios: for the differential diagnosis between ALL and AML when the patient is known to have acute leukemia, for the differential diagnosis among AML FAB subtypes in a patient with known AML, and for the differential diagnosis between ALL FAB subtypes in a patient with known ALL. The specificities were generally high, close to 1. The highest sensitivities in AML were found for +8, t(15;17)(q22;q11), t(8;21)(q22;q22), and -7 (all greater than 0.1), and in ALL for t(9;22)(q34;q11), t(4;11)(q21;q23), and +21 (again all greater than 0.1). In the AML subtypes, the highest sensitivities were 0.89 for t(15;17)(q22;q11) in M3, followed by 0.40 for t(8;21)(q22;q22) in M2, 0.30 for inv(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22) in M4, and 0.16 for t(9;11)(p21;q23) in M5. In the ALL subtypes, the highest sensitivities were 0.71 and 0.11 for t(8;14)(q24;q32) and t(8;22)(q24;q11), respectively, in L3, 0.23 for t(9;22)(q34;q11) in L2, and 0.18 and 0.13 for +21 and t(4;11)(q21;q23), respectively, in L1. The highest (1.0) positive predictive values in the AML versus ALL comparison were found for t(1;3)(p36;q21), inv(3)(q21q26), t(6;9)(p23;q34), t(7;11)(p15;p15), t(8;16)(p11;p13), t(8;21)(q22;q22), t(15;17)(q22;q11), and, as sole anomalies, for +4, +9, and +11. In the reverse comparison, ALL versus AML, positive predictive values of 1.0 were found for t(1;14)(p32-34;q11), dup(I)(q12-21q31-32), t(2;8)(p12;q24), t(8;14)(q24;q32), t/dic(9;12)(p11-12;p11-13), t(10;14)(q24;q11), and t(11;14)(p13;q11). Among the AML subgroups, the highest predictive values were: 1.0 for M3 if t(15;17), 0.91 for M2 if t(8;21), 0.86 for M4 if inv/del(16)/t(16;16), and 0.82 for M5 if t(9;11). Among the ALL subtypes, positive predictive values of greater than 0.8 were reached only for the L3-associated aberrations t(2;8) (1.0), t(8;14) (0.95), t(8;22) (0.87), and dup(I) (0.80). The highest negative predictive values were in AML 0.98 that the disease is not M3 if t(15;17) is not found, and in ALL 0.96 that the patient does not have L3 if a t(8;14) is not detected.     

Overexpression of p21WAF1/CIP1 and MDM2 characterizes serous borderline ovarian tumors

Ovarian epithelial tumors are classically divided into benign, malignant, and borderline or of low malignant potential. It is controversial whether this last group of tumors should be considered benign or malignant. Expression of cell cycle markers has recently been linked to tumor behavior and response to treatment. It has been shown that one of the pathways through which the p53 gene controls the cell cycle is by transactivating p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor. By inhibiting cdks, p21WAF1/CIP1 blocks the G-1 to S-phase transition in the cell cycle. p53 can be regulated by MDM2 (murine double minute-2) through direct inactivation or promotion of its cytoplasmic degradation. In an attempt to investigate the cell cycle checkpoint mechanisms of these tumors, we studied the expression of p53, Ki-67, MDM2, and p21WAF1/CIP1 by immunohistochemistry. We analyzed the expression of these proteins in 19 cystadenomas (8 serous and 11 mucinous), 40 borderline tumors (31 serous and 9 mucinous), and 18 serous carcinomas of the ovary. p21WAF1/CIP1 was expressed in 7 of 19 (37%) benign cystadenomas, 32 of 40 (80%) borderline tumors (93.5% of serous and 33% of mucinous), and in 9 of 18 (50%) serous carcinomas. Ki-67 was only weakly expressed in 8 of 19 (42%) benign cystadenomas, all borderline tumors showed Ki-67 staining in less than 50% of the cells, and 55% of serous carcinomas stained in more than 50% of tumor cells. p53 was absent in all but 1 of the cystadenomas, was expressed in 9 of 40 (22.5%) borderline tumors (25.8% of serous and 11% of mucinous), and in 10 of 18 (55%) carcinomas. All 11 implants of serous borderline tumors expressed p21WAF1/CIP1. Most serous borderline tumors expressed higher levels of MDM2 compared with the benign cystadenomas and carcinomas. Four of the serous borderline implants (40%) expressed MDM2. Coexpression of p21WAF1/CIP1 and MDM2 characterizes serous borderline tumors of the ovary and their implants, which suggests that these cell cycle control proteins are important in these tumors and may be related to tumor progression. Low expression of p53 protein in serous borderline tumors might be in part mediated by MDM2. This suggests that the p53 pathway is intact in most of these tumors, in contrast with carcinomas, in which high expression of p53 has been related to mutations of this gene.     

Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy

Resistance to chemotherapy is a major impediment to the successful treatment of acute leukemia (AL). Expression of genes involved in drug resistance and apoptosis may be responsible for this. This study aimed to investigate the expression of drug resistance (MDR1, MRP1, LRP, BCRP, GSTP1, DHFR) and apoptotic genes (p53, BCL-2, Survivin) in adult acute leukemias and compare them with clinical and hematological findings and response to induction chemotherapy. Eighty-five patients with AL [45 with acute myeloid leukemia (AML) and 40 with acute lymphoblastic leukemia (ALL)] were used as a study group. Real-time PCR results showed that expression level of MDR1 was significantly higher in AML whereas expression of DHFR, BCRP and Survivin was significantly higher in ALL patients. In AML, significant correlation was observed between LRP and MRP1 (r(s)=0.44, p=0.016), LRP and DHFR (r(s)=0.41, p=0.02), MDR1 and BCL-2 (r(s)=0.38, p=0.03). Expression of GSTP1 and LRP correlated with high white blood count (p=0.03 and p=0.03) and BCL-2 with high peripheral blast count (p=0.009). MDR1 expression was significantly associated with the expression of immature stem cell marker CD34 (p=0.002). In ALL, significant association was found between LRP gene and female sex (p<0.0001), LRP and B-ALL patients (p=0.04) and LRP and BCR/ABL positive patients (p=0.004). High expression of MDR1 and BCL-2 in AML and MRP1 gene in ALL was associated with response to induction chemotherapy (p=0.001, p=0.02 and p=0.007 respectively). These results showed the potential clinical relevance of MDR1, MRP1 and BCL-2 in adult patients with acute leukemia in the context of induction chemotherapy.     

Erythropoietic activities in acute leukemia and in malignant lymphoma with or without bone marrow involvement

Erythropoietic activities and immature reticulocyte production were investigated in a total of 157 patients (81 men, 76 women, median age = 42 yr, range = 23 to 65 yr) with acute lymphoid leukemia (ALL, n = 31), acute myeloid leukemia (AML, n = 39), or non-Hodgkin's lymphoma (NHL, n = 87), based on assays of the hemogram, red cell indices, reticulocyte subpopulations, and intramedullary erythroid precursors. There were no significant differences in red blood cell (RBC) counts, blood hemoglobin levels, or erythroid precursors between ALL and AML patients. Reticulocytes in AML patients averaged 1.7 +/- 0.8%, which was higher than in patients with ALL (0.8 +/- 0.3%, p <0.01); the proportion of high-fluorescence reticulocytes (HFR) averaged 4-fold higher in AML versus ALL (p <0.01) and the reticulocyte maturity index (RMI) was higher in AML (20.8 +/- 8.3%) versus ALL (12.4 +/- 6.5%, p <0.01). The RMI was higher in NHL patients with bone marrow (BM) involvement (15.6 +/- 9.4%), compared to those without BM involvement (4.3 +/- 2.1%, p <0.01). The proportion of HFR averaged 11-fold higher in NHL with BM involvement versus NHL without BM involvement. In summary, erythropoietic activity is significantly more active in patients with AML compared to ALL and in patients with NHL with BM involvement, compared to NHL without BM involvement.     

The proportion of abnormal karyotypes in acute leukemia samples related to method of preparation

Bone marrow and peripheral blood were studied from 200 patients with acute leukemia [109 with acute myeloid leukemia (AML), 91 with acute lymphoblastic leukemia (ALL)] who had samples cultured for varying times and who had a mixture of chromosomally abnormal and normal cells. The mean percentage of abnormal metaphase cells increased with culture time. The peak was reached at 48 hours and declined slightly after 72 hours in culture for ALL patients. The mean percentage of abnormal cells increased up to 72 hours in culture for AML patients. In 68 patients (31 AML and 37 ALL), cytogenetic data were available from samples processed with both direct preparations and culture methods. The percentage of abnormal cells increased after culture in 49 patients (23 AML and 26 ALL), while it decreased or remained at the same level in 19 patients. For AML patients, the mean percentage of abnormal cells was significantly different between direct (38%) and cultured preparations (63%), (p less than 0.001). Seven of 9 patients with AML who showed a greater than 50% increase in abnormal cells after culture had either a t(8;21), t(15;17), or abnormalities involving 11q23. The two patients who showed a significant decrease in abnormal cells both had a translocation involving 11q13. Compared with ALL, more AML patients showed greater than 80% abnormal bone marrow metaphase cells at diagnosis or at relapse.     

A multi-institutional study on histopathological characteristics of surgically treated renal tumors: the importance of tumor size

PURPOSE: The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. MATERIALS AND METHODS: Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. RESULTS: Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those < or = 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell carcinoma patients, the percentage of tumors classed as stage > or = T3 was significantly less among tumors < or = 4 cm (5.2%) than those > 4 cm (26.8%) (p < 0.001). The percentage of tumors classed as Fuhrman's nuclear grades > or = 3 was also significantly less among tumors < or = 4 cm (27.3%) than tumors > 4 cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrman's nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. CONCLUSION: In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrman's nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.