Synchronous breast carcinoma and chronic lymphocytic leukemia in a Chinese young female: a rare combination

Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in western countries, however, infrequent in Eastern countries. We report on a rare case of synchronous breast carcinoma and chronic lymphocytic leukemia in a Chinese female patient. A 47-year-old female patient who presented with right breast lump for three month was admitted to our hospital. An ultrasound scan showed two mass in right breast and axillary swollen lymph node. Then, this patient was given right mastectomy and axillary lymph node dissection. Histology report showed invasive ductal carcinoma of the breast (grade I) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Bone marrow was infiltrated by CLL cell. To the best of our knowledge, this is the first report of a Chinese patient suffering from breast carcinoma and chronic lymphocytic leukemia.     

Comparison of immunoperoxidase staining of 3 different types of CD5 antibodies in a spectrum of breast lesions

CONTEXT: We recently described a patient with chronic lymphocytic leukemia who presented with a breast carcinoma that stained positive for CD5 using a commercially available antibody (CD5-4C7, Novocastra, Newcastle upon Tyne, UK). OBJECTIVES: To study the distribution of CD5 immunoreactivity in tissue sections of a variety of benign and malignant breast lesions using the antibody CD5-4C7 and to compare the results with those obtained with 2 other commercially available CD5 antibodies (CD5/54/F6, Dako, Ely, Cambridgeshire, UK, and CD5/54/B4, Novocastra). DESIGN: Paraffin sections of 102 breast biopsy specimens with various diagnoses were examined using the avidin-biotin immunoperoxidase complex technique. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: The staining results obtained with CD5-4C7 were different from those obtained with the other 2 antibodies. With 4C7, the normal and benign biopsy specimens showed varying numbers of positive epithelial cells and lymphocytes. Heterogeneous positive staining was also present in 47 (78%) of 60 invasive female breast carcinomas and in all 3 male breast carcinomas examined. A statistically significant correlation was found between CD5 positivity and tumor grade, with grade 3 tumors being less likely to be CD5 positive than grades 1 and 2 (P =.0035). No correlation was found between CD5 positivity and patient's age, tumor histologic type, axillary lymph node status, or progesterone receptors. On the other hand, the CD5/54/F6 and CD5/54/B4 antibodies only stained lymphocytes and occasional normal breast ducts, mostly those showing apocrine metaplasia. All other normal benign and malignant epithelial cells were negative. CONCLUSIONS: Positive staining for CD5 using the antibody 4C7 is seen in normal and benign breast tissue and 78% of invasive breast carcinomas. The positivity is more common in low-grade tumors. No significant staining was seen with the 2 other CD5 clones used in this study. The significance of the positive staining obtained with CD5-4C7 is not obvious, but this clone may be more sensitive than the others, or it may be recognizing an epitope shared by another antigen.     

Fine-needle aspiration diagnosis of squamous cell carcinoma in a lymph node involved with small lymphocytic lymphoma: case report and review of the literature

Diagnosis of two distinct malignant entities existing concurrently and at the same location (synchronous malignancy) by fine- needle aspiration (FNA) is unusual but may occur. Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) in particular is associated with an increased incidence of secondary tumor, likely due to associated immunodeficiency. Co-occurrence of some carcinomas such as squamous cell carcinoma (SCC), may show especially aggressive behavior. A 57-year-old Caucasian male presented with recurrent upper extremity lymphedema and diffuse lymphadenopathy of the axillary and cervical regions. FNA of a large cervical lymph node was diagnostic for both atypical lymphocytic proliferation and SCC. Flow cytometric analysis showed the atypical lymphocytic proliferation to be positive for CD5, CD23, CD19, CD20, HLA-DR, CD38, and the population was kappa light chain restricted. These cells were negative for CD-10 and FMC-7 antigens, suggesting a phenotype of B-cell SLL/CLL. We report a rare occurrence of metastatic SCC to a lymph node infiltrated by SLL/CLL. The diagnosis was achieved by a combination of cytomorphologic examination of FNA smears, immunohistochemical staining of cell block material, and flow cytometry on the sample obtained by FNA. To the best of our knowledge, only three cases of SCC metastasis to SLL/CLL diagnosed by FNA have been reported in the English literature. Though rare, awareness of such a possibility and careful cytological examination under the appropriate clinical conditions is warranted.     

Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix.

Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies of CIN lesions, primary cervical carcinoma, and metastases may shed light on the relative importance of various genetic alterations involved in the progression of CIN to invasive carcinoma. We examined tumor material from 10 patients with squamous cell carcinoma of the uterine cervix and synchronous CIN lesions and lymph node metastases. The CIN component, invasive carcinoma, and lymph node metastases were analyzed separately for loss of heterozygosity (LOH) on the following loci: VHL (3p21), HLA region (6p22-23), PGL (11q 22-24), E6 associated protein (15q11-13), TP53 (17p13), DCC (18q21.1), and chromosomes 1, 2, 4, 9, 20, and X. Using immunohistochemistry, the expression of the EGF receptor, ERBB2, and TP53 was determined. In CIN lesions, frequent LOH was found at chromosome arms 3p, 6p, and 11q. Primary invasive carcinoma showed additional LOH at chromosome arms 6q, 17p, and 18q. In lymph node metastases, an additional locus on the X chromosome displayed LOH. All carcinomas and synchronous lesions but one showed high expression levels of the EGF receptor. TP53 staining, when present, was found in all synchronous lesions. Focal staining of ERBB2 was found in one CIN lesion, two invasive carcinomas, and four metastases. The molecular alterations accumulated in a fashion that paralleled the progression of the tumors. These results indicate that cervical tumorigenesis occurs in a stepwise fashion, including infection and integration of oncogenic HPV and several specific genetic alterations. Genes Chromosomes Cancer 26:346-354, 1999.     

乳腺典型髓样癌与不典型髓样癌临床病理分析

目的探讨乳腺典型与不典型髓样癌的临床病理特征和生物学行为差异。方法对乳腺典型髓样癌及不典型髓样癌各20例临床病理资料进行分析,并采用S-P法检测nm23、E-cad、p53、ER、PR、c—erbB—2、CD45RO和CD20的表达。结果典型髓样癌组,癌细胞合体性结构〉75％,无腺管结构,间质见弥漫性淋巴细胞浸润;不典型髓样癌组,可见腺管结构,间质无或少量淋巴细胞浸润。免疫组化检测典型髓样癌nm23、E—cad阳性表达均高于不典型髓样癌。典型组随访12～84月（平均37个月）,均无腋下淋巴结转移,均健在;不典型组随访9～84月（平均29．5个月）,腋下淋巴结转移4／20例,其中4例分别于术后1—3年内死亡。结论①要严格掌握乳腺典型髓样癌与不典型髓样癌的病理诊断标准。②不典型髓样癌不完全等同“乳腺浸润性导管癌伴髓样特点。”③乳腺典型与不典型髓样癌的预后不同,前者明显优于后者。     

Follicular lymphoma mimicking marginal zone lymphoma in lymph node: a case report

Nodal follicular lymphoma (FL) is typically composed of follicular or nodular proliferation of small cleaved lymphoid cells, presumably derived from germinal center (GC) B cells. The hallmark of FL is t(14;18)(q32;q21) chromosomal translocation, which juxtaposes anti-apoptotic gene BCL2 to immunoglobulin heavy chain (IGH) promoter. Reflecting this background, FL cells are immunohistochemically positive for BCL2 as well as GC B cell markers CD10 and BCL6. It is known that low grade B-cell lymphomas, including FL, chronic lymphocytic leukemia/small lymphocytic lymphoma, and marginal zone lymphoma, are sometimes associated with marginal zone differentiation or plasmacytic differentiation. The marginal zone differentiation obscures the morphological differences among these, providing diagnostic challenges for histopathologists. In this paper, we present a case of FL, originally mimicking marginal zone lymphoma in the axillary lymph node. Subsequent bone marrow biopsy showed paratrabecular infiltration of small to medium-sized lymphoid cells. Immunohistochemical analysis of the bone marrow biopsy together with histopathology and flow cytometry of the axillary lymph node led to a final diagnosis of FL with marginal zone differentiation in the axillary lymph node and its bone marrow infiltration. Our case illustrates and reconfirms the importance of clinicopathological correlation which leads to a correct diagnosis.     

Metastatic breast carcinoma with appearance resembling micropapillary ductal carcinoma in situ.

AIM--To investigate tumour in an axillary lymph node resembling micropapillary ductal carcinoma in situ. METHODS--Sections of tumour in the breast and axillary lymph node were stained with haematoxylin and eosin, and immunohistochemically with antibodies to basement membrane and myoepithelial cells. RESULTS--Tumour in both the breast and axillary lymph node contained areas resembling micropapillary ductal carcinoma in situ. Surrounding these islands, there was a band of eosinophilic material resembling basement membrane and spindle cells that in places appeared to lie outside the basement membrane. Micropapillary tumour at both sites showed weak and discontinuous staining for collagen IV and laminin. The spindle cells stained for alpha-smooth muscle actin, but not for S100. By contrast, immunohistochemistry showed complete rings of basement membrane and myoepithelial cells around definite ductal carcinoma in situ and normal breast lobules and ducts. CONCLUSIONS--Invasive primary and metastatic carcinoma of the breast can have a growth pattern resembling micropapillary ductal carcinoma in situ.     

Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature

Spontaneous regression (SR) of cancer is a rare but well-documented biological phenomenon. However, the mechanism remains to be elucidated. We herein report a case of the SR of breast cancer at both the primary site and metastatic axillary lymph node with spontaneously-induced T cell-mediated immunological responses. A 52-year-old female with a lump in the left axilla was diagnosed to have a small breast carcinoma with a distinct axillary lymph node metastasis. During the preoperative systemic examination, she was diagnosed to have severe type 2 diabetes mellitus, was treated with insulin, and the hyperglycemia was normalized after one month. Surgery for left breast cancer was then performed. The postoperative histopathological examination revealed the SR of breast cancer at both the primary site and metastatic axillary lymph node. Immunohistochemical studies revealed that estrogen receptor positive, AE1/AE3-positive ductal carcinoma completely underwent necrosis associated with extensive infiltration of CD3-positive T cells in the tumor nodule in the lymph node. In addition, primary ductal carcinoma cells also underwent single cell necrosis with infiltration of T cells with lymph follicle-like organization of B cells in the mammary gland. The features were suggestive that the tumor eradication in the metastatic lymph node and regression of the primary ductal carcinoma could be due to host T cell response to the ductal carcinoma. As far as we know it is the first report that shows the spontaneous regression of breast cancer, probably due to the spontaneously-induced T cell response.     

CD44 expression and axillary lymph node metastasis in infiltrating ductal carcinoma of the breast

Metastasising ability connotes one of the most important life-threatening properties of malignant neoplasms. Recent studies indicate that CD44 proteins, multifunctional cell adhesion molecules which contribute to "homing" of lymphocytes to lymph nodes as well as cell-cell and cell-matrix interactions, are potential markers of tumour progression. However, whether CD44 expression by human tumours contribute to increased metastatic risk remains controversial. In an attempt to clarify its role in breast cancer, we have investigated the correlation between CD44 expression by breast carcinoma and the presence of axillary lymph node metastases. CD44 expression was detected using a standard immunoperoxidase method on formalin-fixed, paraffin-embedded, primary infiltrating ductal breast carcinoma tissues taken from 60 female patients who underwent mastectomy with axillary node clearance. Tumours were graded according to the modified Bloom and Richardson criteria. 62% of patients had histologically-proven lymph node metastasis. 40% of primary cancers exhibited cytoplasmic membrane immunopositivity for CD44. 46% of primary tumours which have metastasied to axillary lymph nodes were CD44 positive whereas 30% of tumours which have not metastasised expressed CD44. CD44 positivity was expressed by 20% of grade 1, 31% grade 2 and 58% grade 3 tumours. Our results suggest that CD44 may have a role in the progression of breast cancer and emphasise the need to investigate its interaction with other mechanisms of cancer advancement.     

妊娠相关性乳腺癌和伴妊娠样改变的乳腺癌

目的 探讨妊娠相关性乳腺癌和伴妊娠样改变的乳腺癌病理组织学特点及其免疫表型。方法 从1050例乳腺癌病理资料中查出全部妊娠相关性乳腺癌18例和伴有妊娠样改变的乳腺癌9例，详细观察HE切片的组织形态学特点，用PV9000二步法进行免疫组化染色。结果 妊娠相关性乳腺癌肿瘤直径1．5～6．0cm(中位数3．8cm)，淋巴结转移率为84．6％；16例为浸润性导管癌，2例为黏液癌；11例伴有小叶癌化，7例有多形性癌成分，6例伴有大汗腺癌样改变。伴泌乳样改变的乳腺癌全部为浸润性导管癌，肿瘤直径1．5～9．Ocm(中位数4．9cm)，淋巴结转移率100％；有小叶癌化者7例，2例伴有大汗腺癌样改变。免疫组化两者均100％表达E-cadherin，66．7％表达p53，表达ER分别为40．O％和77．8％，PR分别为21．4％和44．4％．c-erbB-2分别为46．7％和44．4％,bcl-2分别为40．0％和55．5％，EGFR分别为35．7％和22．2％,Ki-67平均阳性指数为46．87和39．63。结论 妊娠相关性乳腺癌和伴妊娠样改变的乳腺癌在组织形态上有一定特点，主要发生于导管癌，两者都有较高的小叶癌化率；淋巴结转移率都很高,PR的表达率较低，提示预后不好。     

Chromosome 8p alterations in sporadic and BRCA2 999del5 linked breast cancer

Chromosomal losses involving the short arm of chromosome 8 are frequent in a variety of tumour types, including breast cancer, suggesting the presence of one or more tumour suppressor genes in this region. In this study, we have used 11 microsatellite markers to analyse loss of heterozygosity (LOH) at chromosome 8p in 151 sporadic breast tumours and 50 tumours from subjects carrying the BRCA2 999del5 mutation. Fifty percent of sporadic tumours compared to 78% of BRCA2 linked tumours exhibit LOH at one or more markers at 8p showing that chromosome 8p alterations in breast tumours from BRCA2 999del5 carriers are more pronounced than in sporadic breast tumours. The pattern of LOH is different in the two groups and a higher proportion of BRCA2 tumours have LOH in a large region of chromosome 8p. In the total patient material, LOH of 8p is associated with LOH at other chromosome regions, for example, 1p, 3p, 6q, 7q, 9p, 11p, 13q, 17p, and 20q, but no association is found between LOH at 8p and chromosome regions 11q, 16q, 17q, and 18q. Furthermore, an association is detected between LOH at 8p and positive node status, large tumour size, aneuploidy, and high S phase fraction. Breast cancer patients with LOH at chromosome 8p have a worse prognosis than patients without this defect. Multivariate analysis suggests that LOH at 8p is an independent prognostic factor. We conclude that chromosome 8p carries a tumour suppressor gene or genes, the loss of which results in growth advantage of breast tumour cells, especially in carriers of the BRCA2 999del5 mutation.


Keywords: chromosome 8; BRCA2; LOH; breast cancer     

Genetic alterations in 'normal' luminal and myoepithelial cells of the breast

Chromosomal loci exhibiting loss of heterozygosity (LOH) at high frequency in invasive breast cancer have been investigated in 'normal' breast tissue from patients with carcinoma and from reduction mammoplasty specimens. Duct-lobular units dissected from paraffin-embedded tissues and 485 'normal' luminal and myoepithelial cell clones were studied. Overall, LOH was found in normal cells in 5/10 breast cancer cases and 1/3 reduction mammoplasty specimens. LOH was identified in normal cells adjacent to and distant from the tumour. In one case, all luminal and myoepithelial samples exhibited loss of the same allele on chromosome 13q. One case in which the patient had a germline truncating mutation in the BRCA1 gene exhibited LOH on 17q in 3/33 normal clones. One of these clones showed loss of wild-type allele indicating gene inactivation. This sample also had LOH at markers on chromosomes 11p and 13q. One of 93 clones from three reduction mammoplasties showed allele loss at a locus on chromosome 13q. The identification of LOH in breast lobules suggests that they may be clonal. The demonstration of genetic alteration in luminal and myoepithelial cells provides evidence for the presence of a common stem cell for the two epithelial cell types. LOH has been demonstrated in normal tissues near and away from the carcinoma, suggesting that genetic alterations are likely to be more heterogeneous and widespread than is currently envisaged, and probably occur very early in breast development. Homozygous deletion of BRCA1 per se does not appear to provide clonal advantage.     

Indolent mantle cell lymphoma with nodal involvement and mutated immunoglobulin heavy chain genes

Mantle cell lymphoma (MCL) is typically considered an aggressive but incurable neoplasm composed of cyclin D1+ monoclonal B-cells with a t(11;14)(q13;q32) and usually unmutated immunoglobulin (Ig) genes. Although it has been suggested that a more indolent leukemic disorder exists with the same phenotype and genotype but with mutated Ig genes, others have considered these cases to be variants of chronic lymphocytic leukemia. We present a case of an indolent MCL that was documented with cyclin D1 expression in a lymph node biopsy performed more than 12 years ago. The patient has peripheral blood involvement with a lymphocyte count in the reference range, variable thrombocytopenia, and minimal adenopathy but is otherwise well, never having received any antineoplastic therapy. Study of peripheral blood samples from 2002 revealed a CD5-variable B-cell monoclonal proliferation with a t(11;14)(q13;q32) plus other karyotypic abnormalities, positive fluorescence in situ hybridization studies for the CCND1/IgH translocation, and clonal Ig gene rearrangement with mutated Ig genes (95.7% homology to VH 4-31). The subtle but diagnostic lymph node biopsy in this case helps to further support that an indolent t(11;14) monoclonal lymphocytosis with mutated Ig genes can represent an MCL variant rather than chronic lymphocytic leukemia.     

乳腺癌患者妊娠次数与腋窝淋巴结转移的关系研究

目的探讨乳腺癌患者妊娠次数与腋窝淋巴结转移之间的关系。方法171例乳腺癌患者按妊娠次数分为妊娠1次，2次及2次以上共3组。统计该3组患者各自发生腋窝淋巴结转移的患者比例及发生转移的腋窝淋巴结在所检测的淋巴结中的比例，应用X2检验分析不同组别间腋窝淋巴结转移阳性患者比例的差异，阳性转移淋巴结比例之间的差异，从而探讨乳腺癌患者的妊娠次数与其腋窝淋巴结转移例数及转移个数之间的关系。结果妊娠1次、妊娠2次及妊娠2次以上组发生腋窝淋巴结转移的比例分别为34．78％、50％、64．10％。随妊娠次数增加，发生腋窝淋巴结转移的比例逐渐增高。其中妊娠2次以上患者组发生腋窝淋巴结转移的比例明显高于妊娠1次患者组发生腋窝淋巴结转移的比例（64．10％掷34．78％），2者相比差异有显著性（P：0．012）。妊娠1次、妊娠2次及妊娠2次以上组腋窝淋巴结发生转移的比例分别为44．58％、44．18％、52．97％。妊娠2次以上患者组腋窝淋巴结发生转移的比例明显高于妊娠2次患者组腋窝淋巴结发生转移的比例（52．97％协44．18％），2者相比差异有显著性（P=0．025）。但妊娠1次组腋窝淋巴结发生转移的比例与妊娠2次组及妊娠2次以上组相比，差异均无显著性（P=0．948，P=0．167）。结论妊娠次数较少的患者组发生腋窝淋巴结转移的比例相对较小，发生转移的腋窝淋巴结数目也相对较少。乳腺癌患者的妊娠次数与乳腺癌的腋窝淋巴结转移有关。乳腺癌患者的妊娠次数对判断乳腺癌患者的腋窝淋巴结转移有一定的意义。     

Patterns of loss of heterozygosity at loci from chromosome arm 13q suggest a possible involvement of BRCA2 in sporadic breast tumors

Loss of heterozygosity (LOH) at loci from chromosome I3 is frequently observed in breast cancer. Chromosome 13 contains at least two cancer genes, the well-characterized RB1 gene located at 13q 14 and the breast cancer-susceptibility gene, BRCA2, recently localized to 13q 12. To investigate the possible involvement of BRCA2 in sporadic breast tumors, we looked at LOH at eight microsatellite (CA)ⁿ markers distributed along chromosome 13 in a panel of 59 primary breast carcinomas. We show that some LOH does not include the RB1 locus and is associated with the BRCA2 gene region.     

Intraoperative evaluation of sentinel lymph nodes for breast carcinoma: current methodologies

Sentinel lymph node biopsy is an important new addition to the surgical management of patients with breast carcinoma. Sentinel nodes have a higher chance of containing metastases than do nonsentinel nodes. Sentinel lymph node biopsy provides an opportunity to stage breast carcinoma patients more accurately and to modify subsequent treatment. One of the most exciting current roles of sentinel lymph node biopsy is the ability to stage patients intraoperatively, allowing a one-step axillary lymph node dissection if the sentinel lymph node contains metastatic carcinoma. Currently, intraoperative evaluation of sentinel lymph nodes is performed using imprint cytology with or without rapid cytokeratin staining, frozen sectioning with or without rapid cytokeratin staining, scrape preparations, or some combination of these techniques. We review the relative strengths and weaknesses of these different methodologies. A great deal of controversy exists regarding the management of patients with metastatic breast carcinoma, particularly those patients with occult and micrometastatic disease. These issues are beyond the scope of this article.     

The gene for hereditary breast-ovarian cancer, BRCA1, maps distal to EDH17B2 in chromosome region 17q12-q21

A gene for hereditary breast and ovarian cancer, BRCA1, hasbeen mapped to chromosome 17q12–q21. This gene is responsiblefor cancer susceptibility in the majority of families with multiplecases of ovarian cancer and early-onset breast cancer. We reportlinkage results of a family with 10 cases of breast cancer anda single case of ovarian cancer. A recombinant event in thisfamily places BRCA1 distal (telomeric) to the locus EDH17B2,which codes for the enzyme estradiol 17ß-dehydrogenaseII. This recombinant is based on the appearance of breast cancerin a 45 year old woman. Under our genetic model, we estimatethe probability that this woman carries a BRCA1 mutation tobe 94%. These data further reduce the region of assignment ofBRCA1 on chromosome 17q12–q21 and should expedite positionalcloning of this important gene.     

Pseudoneoplastic proliferation of histiocytes with paclitaxel-induced ultrastructural changes in a mastectomy specimen

A 49-year-old Hispanic woman with a T4N1M0 infiltrating duct carcinoma of the left breast underwent four courses of FAC (doxorubicin 86 mg, 5-fluorouracil 860 mg, cyclophosphamide 86 mg, and dexamethasone 10 mg) adjuvant chemotherapy plus four courses of paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ) and subsequent mastectomy. The tumor shrunk from 6.5 cm to 2.5 cm after the treatment. The residual tumor in the surgical specimen measured 1.5 cm with eight positive out of 24 axillary lymph nodes. The tumor showed typical chemotherapy changes and a massive proliferation of histiocytes that mimicked a neoplasm. A nodular proliferation of the same cells in one axillary node raised the impression of a second malignant tumor in the breast spreading to the node. The histiocytic cells contained lamellar and coarse periodic acid-Schiff-positive material distending their cytoplasm and they were strongly positive for CD68 and negative for CD1a, pan keratin, and S-100. These findings ruled out histiocytoid carcinoma, granular cell tumor, and Erdheim-Chester disease. The proliferating histiocytes had ultrastructural findings of paclitaxel-induced cytotoxicity with disorganized stacks of intermediate filaments positive for vimentin by immunostains and fewer masses of tubulin. The treated breast carcinoma cells were tubulin-positive but the proliferating histiocytes were tubulin-negative.     

A large multisite cancer family is linked to BRCA2.

We identified a large French-Canadian family with 21 cases of breast cancer, including two affected brothers. Segregation of markers from chromosome 13q in this family showed linkage to the BRCA2 gene locus (lod = 3.67 at D13S289). A number of cancers of other types occurred in this family, including three cases of prostate cancer and two cases of lymphoma. The penetrance of breast cancer among BRCA2 carriers is estimated to be 75% to the age of 70.     

Expression of DNA-PKcs and Ku86, but not Ku70, differs between lymphoid malignancies

We have investigated the role of DNA-dependent protein kinase (DNA-PK) and related it to proliferation and maturation of different lymphoid malignancies. DNA-PK and Ki-67 protein content was investigated in tumour samples of lymphoid malignancies, obtained from patients with low- and high-grade lymphomas, acute lymphoblastic leukaemia and multiple myeloma. All patients were untreated before sampling. Normal bone marrow, reactive tonsillar tissue and ordinary lymph node tissue were used as controls. We show here that lymphoid malignancies display differences in DNA-PK protein expression. Low-grade lymphoma, appearing as chronic lymphocytic leukaemia (CLL) displayed a significantly lower frequency of cells staining positive for DNA-PKcs and Ku86, but surprisingly not for Ku70, compared with acute lymphoblastic leukaemia (ALL) cells. When material from individual CLL patients was investigated, cells from lymph nodes showed a higher frequency of positive cells with respect to all DNA-PK subunits, compared with CLL cells infiltrating the bone marrow. High-grade lymphoma lymph node samples showed an increased frequency of cells staining positive for DNA-PKcs, Ku86 and Ki-67 compared with lymph node samples from low-grade lymphoma patients. Again, no difference in the Ku70 levels between the two lymphoma entities was noted. In multiple myeloma, the frequency of cells with positive staining for DNA-PKcs was similar to that detected in ALL and high-grade lymphoma. We conclude that with the exception of multiple myeloma, expression of DNA-PK coincides with the degree of maturation of lymphoid malignancies. In low- and high-grade lymphoma, DNA-PK is associated with the proliferation rate.