Biomedical subjects

A Cardesa

Publications and source records attributed to A Cardesa.

At least 19 recordsLinked to original sources

PubMed2006

ATM gene expression is associated with differentiation and angiogenesis in infiltrating breast carcinomas.

UNLABELLED: The product of the ATM gene, mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a key role in the detection and repair of DNA double-strand breaks. A-T is defined by progressive cerebellar ataxia, telangiectasia, sensitivity to ionising radiation and genomic instability with cancer predisposition. On the other hand, increased angiogenesis is essential for tumor growth and metastasis. The aim of this study was to investigate ATM expression in breast carcinomas and its relationship to neoangiogenesis. METHODS AND RESULTS: Fifty-two breast tumors from 51 patients, 38 of them with concomitant in situ component (CIS), were analyzed by immunohistochemistry for the expression of ATM. CD34 expression was used for the morphometric evaluation of vasculature. ATM was positive in 1 to 10% of normal epithelial cells. ATM expression was reduced in 55.8% of infiltrating carcinomas, non-reduced in 34.6%, and increased in 9.6%. Expression of ATM in CIS was similar to the infiltrating component in 71% of cases and reduced in 23.7% of them. High-grade ductal infiltrating carcinomas showed lower ATM expression than low-grade ones. Reduced ATM expression also correlated with increased microvascular area. CONCLUSIONS: Reduced ATM expression in breast carcinomas correlated with tumor differentiation and increased microvascular parameters, supporting its role in neoangiogenesis and tumor progression in breast carcinogenesis.

Antigens, CD34↗

PubMed2004

Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases.

AIMS: Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely. METHODS AND RESULTS: All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High-molecular-weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12-35 months). CONCLUSIONS: ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.

Adult↗

PubMed2004

Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy.

OBJECTIVE: We analyzed the value of topoisomerase IIalpha (Topo II) in predicting the clinical response to anthracycline-based neoadjuvant chemotherapy in breast cancers and the potential changes in Topo II after chemotherapy. In parallel, HER2, which is commonly coexpressed with Topo II, and p53, a modulator of chemotherapy activity, were also analyzed. METHODS: Forty-one patients with primary breast cancer and treated with neoadjuvant anthracycline-based chemotherapy (FAC or FEC) were included for the present study. Topo II, HER2 and p53 expression were measured by immunohistochemistry in pre and post chemotherapy (at the time of surgery), tumor specimens and the results were correlated with the clinical response. RESULTS: Topo II was overexpressed in 16 of 41 (31%) tumors before treatment, and this overexpression was significantly associated with clinical response (p = 0.03). HER2 and p53 were unrelated to response. Notably, Topo II overexpression, but not HER2 or p53, was lost in specimens after chemotherapy (p = 0.01). CONCLUSION: The observed link between Topo II and the clinical response to neoadjuvant anthracycline-based chemotherapy, together with its loss after chemotherapy, implies that Topo II deserves further testing in a prospective setting as a predictive marker.

Adult↗

PubMed2003

Plexiform ameloblastoma presenting as a sinonasal tumor.

Ameloblastomas are the most frequent odontogenic tumours, accounting for 1% of all tumours of the maxilla and mandible. Sinonasal ameloblastomas are most common between the ages of 55 and 65, and mandibular ameloblastomas between 40 and 50. Incidence is higher in males than in females, and there are no differences between races. These locally aggressive tumours originate in the mandible in 80% of cases and in the maxilla in 15-20%. We report an unusual primary nasosinusal ameloblastoma presented in a 68-year-old male. The tumour was completely resected by (para)lateral rhinotomy and treated with postoperative radiotherapy. Histological analysis demonstrated a plexiform ameloblastoma. The patient remains well without disease after 50 months of postoperative follow-up.

Aged↗

PubMed2003

Sinonasal tubulopapillary low-grade adenocarcinoma. Histopathological, immunohistochemical and ultrastructural features of poorly recognised entity.

We present the clinicopathological, histological and immunohistochemical findings of six cases of primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract with ultrastructural examination in one case. Due to its unique features, we believe that primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract represents a tumour entity different from any tumours generally recognised in the sinonasal region. Our cases had an equal sex incidence, with an age range of 44-76 years. The tumour has a tendency to recur, but none of our six patients developed metastases. We feel that it is important to separate this tumour entity from other types of sinonasal adenocarcinomas that exhibit a papillary growth pattern, as they frequently pursue a much more aggressive clinical course than the tumours in this study.

Adenocarcinoma↗

PubMed2001

Placental malaria is associated with cell-mediated inflammatory responses with selective absence of natural killer cells.

Immunosuppression, particularly of cell-mediated responses, has classically been thought to play a major role in the increased susceptibility to malaria observed in pregnant women. An immunohistochemical characterization of the inflammatory infiltrate in a group of 41 placentas from women living in a Plasmodium falciparum-hyperendemic area in Tanzania revealed a marked increase in the number of monocytes and macrophages and cytotoxic T cells in the intervillous space of placentas with active malaria infection, compared with noninfected placentas, placentas from women with past infection, and a control group of placentas from Spain. This increase was associated with the severity of the infection. High numbers of monocytes and macrophages were associated with low birth weight. We also detected a complete absence of NK cells in the intervillous space in all placentas. This apparently physiological absence of NK cells may contribute to hindering the clearance of the parasite. These results indicate that placental malaria does not appear to be associated with cell-mediated immunosuppression. The role of the absence of NK cells in increased susceptibility to malaria needs to be further elucidated.

Animals↗

PubMed2001

Expression of cathepsins B and S in the progression of prostate carcinoma.

Cathepsins B and S (CatB, CatS) are lysosomal cysteine proteases which, among other functions, appear to play a role in cancer progression in different tumor models due to their matrix-degrading properties. To investigate their possible involvement in the development of prostate carcinoma, we immunohistochemically analyzed CatB and CatS in 38 primary human prostatic adenocarcinomas, as well as concomitant high-grade prostatic intra-epithelial neoplasia, nodular hyperplasia and normal tissue. CatB expression was observed in 28 (74%) and CatS in 32 (84%) carcinomas, being concomitant in 24 cases (63%). High-grade intra-epithelial neoplasia expressed CatB in 20/23 cases (87%), and a similar result was obtained for CatS, with expression of both coinciding in 18 cases (78%). In non-neoplastic tissue, strong expression of both proteases was observed in macrophages, inflamed glands and transitional metaplasia, whereas atrophic glands and basal cells of normal glands displayed intense CatB positivity. We conclude that CatB and CatS are often expressed together in neoplastic prostatic cells from pre-invasive to invasive and clinically detectable stages, suggesting a putative role in local invasion, though other functions cannot be ruled out.

Adenocarcinoma↗

PubMed2001

Tissue macroarrays ("microchops") for gene expression analysis.

We describe a simple system of tissue arraying with multiple tissue fragments obtained with a biopsy punch from selected areas of paraffin blocks. The new blocks thus constructed allow multiple tissue sections in which the uniform shape of the fragments coupled with a geometrical display and a significant amount of tissue per case allows a dependable, cost-effective way to screen tumors or other kinds of tissues with techniques such as immunohistochemistry. This system avoids the disadvantages of previous laborious methods of tissue arraying, such as expensive equipment and scarce tissue sampling, and it can be implemented in any institution with minimal cost and elaboration.

DNA, Neoplasm↗

PubMed2001

Renal expression of intercellular adhesion molecule-1 in immunoglobulin A nephropathy: tubulointerstitial injury and prognosis.

In immunoglobulin A nephropathy (IgAN), the abnormal expression of intercellular adhesion molecule-1 (ICAM-1) on proximal tubule epithelium is associated with the glomerular and interstitial infiltration of leucocytes, but its clinical significance remains uncertain. We analysed the relationship between the ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes, macrophages (CD14) and T lymphocytes (CD3) with the histologic features, proteinuria and serum creatinine at the time of renal biopsy and after 2.42 years in 45 patients with IgAN and after 1.8+/-1.5 years in 29 patients with non-glomerulonephritis (non-GN). In IgAN, ICAM-1+ tubule epithelium was 0.1+/-0.18 (x+/-SD), and this was associated with extracapillary proliferation (up to 20% of Bowman's space), glomerular sclerosis involving less than 50% of glomerular area, interstitial cellular infiltration, tubular atrophy and proteinuria level. ICAM-1+ interstitial leucocytes were correlated with glomerular sclerosis involving less than 50% of glomerular area, glomerular sclerosis involving more than 50% of glomerular area, tubular atrophy, interstitial fibrosis and serum creatinine level. In patients with an increase of 50% in serum creatinine, ICAM-1+, CD14+ and CD3+, interstitial leucocytes were significantly outnumbered than in patients with stable serum creatinine. In non-GN, ICAM-1+ tubule epithelium was 0.02+/-0.04 (U=344, P<0.05, vs IgAN), and this was inversely correlated with the percentage of the normal glomeruli and associated with glomerular sclerosis covering more than 50% of glomerular area, tubular atrophy and serum creatinine level. The association between tubular ICAM-1 and proteinuria and the association between interstitial ICAM-1+, CD14+ and CD3+, leucocytes and renal failure at presentation and the deterioration in IgAN in contrast with non-GN suggest that tubular and interstitial expression of ICAM-1 may be a marker of tubulointerstitial disturbance in IgAN.

Adult↗

PubMed2001

Differential expression of cdc25 cell-cycle-activating phosphatases in human colorectal carcinoma.

cdc25 is a family of cell-cycle phosphatases that activate the cyclin-dependent kinases. cdc25A and B, but not C, have oncogenic potential in vitro. In this study, we analyzed the possible implication of cdc25 genes in the progression of colorectal tumors. RNA and DNA were extracted from 34 paired tumor and normal colorectal tissues and examined by Northern blot, RT-PCR, and Southern blot, respectively. Protein expression was analyzed by Western blot in a subset of normal and tumor samples. The expression levels were correlated with the clinicopathologic characteristics and survival of the patients. cdc25B mRNA was overexpressed in 19 carcinomas (56%). A significant correlation was observed between high cdc25B mRNA levels and the relapse-free, overall, and cancer-related survival of the patients. The cdc25B2 splicing variant was detected in 27 carcinomas (79%) but only in 9 normal samples (26%) and was associated with the grade of the differentiation of the tumors. cdc25A mRNA was overexpressed in four tumors (12%) and cdc25C1 mRNA was overexpressed in nine tumors (26%). A new cdc25C2 splicing variant lacking exon 4 and 5 was identified in all of the tumors and in 56% of the normal samples. No amplifications or gene rearrangements of these genes were detected. In conclusion, these findings indicate that cdc25 isoforms and splicing variants are differentially regulated in colorectal carcinomas and may participate in the development of these tumors. Additionally, the correlation between cdc25B mRNA levels and the survival of the patients also suggest that the cdc25B isoform may be involved in the progression of the disease.

Adult↗

PubMed2001

Expression of cyclin D1 and p53 and its correlation with proliferative activity in the spectrum of esophageal carcinomas induced after duodenal content reflux and 2,6-dimethylnitrosomorpholine administration in rats.

Alterations in expression of the p53 and cyclin D1 genes have been implicated in the development of esophageal carcinomas in both humans and animal models. We hypothesize that altered expression of cyclin D1 and p53 may be involved in the sequential development of esophageal carcinomas with glandular differentiation induced by the carcinogen, 2,6-dimethylnitrosomorpholine (DMNM) in rats with duodenal content reflux esophagitis. In the present study Sprague-Dawley rats were given DMNM 15 days after performing an esophago-jejunostomy in order to induce chronic duodenal content reflux esophagitis. Expression and localization of p53, cyclin D1 and Ki-67 were examined by immunohistochemical analyses. Twenty of 24 animals developed different types of esophageal carcinomas, including pure squamous carcinoma, adenosquamous carcinoma and pure adenocarcinoma. Undifferentiated basaloid areas were frequently observed in these tumors. Cyclin D1 overexpression was observed in hyperplastic lesions and increased through dysplasia and in undifferentiated areas of infiltrating carcinoma. Cyclin D1 expression coincided with increased Ki-67 expression and decreased along with cell differentiation. The p53 immunohistochemical pattern was parallel to that of cyclin D1, although the percentage of positive cells was usually smaller in all lesions and increased p53 expression started at the dysplastic stage. These findings suggest that overexpression of cyclin D1 may be an early event in DMNM-induced rat esophageal tumorigenesis, causing increased proliferation of esophageal stem cells. Abnormal p53 expression may then be required to promote the development of neoplastic transformation from dysplastic epithelium through invasive phenotype, being more evident in cancer cells with squamous differentiation.

Adenocarcinoma↗

PubMed2001

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Adenocarcinoma↗

PubMed2000

cdc25a and the splicing variant cdc25b2, but not cdc25B1, -B3 or -C, are over-expressed in aggressive human non-Hodgkin's lymphomas.

cdc25 is a family of phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and -B, but not -C, have been shown to have oncogenic potential. Three different splicing variants of the cdc25B gene, cdc25B1, -B2 and -B3, have also been identified. Experimental studies suggest that cdc25B2 may be more active in vivo than cdc25B3 and -B1, but the relative expression of these splicing variants in human tumors is not known. In this study, we have analyzed the expression of cdc25A, -B1, -B2, -B3 and -C mRNA in 9 non-neoplastic lymphoid samples, 89 non-Hodgki&ngrave;s lymphomas and 9 hematological cancer cell lines by semi-quantitative RT-PCR. cdc25A, -B and -C protein expression was examined by Western blot. Normal peripheral blood lymphocytes and reactive tissues expressed cdc25B1 and -B3 mRNA and very low or undetectable levels of cdc25A, -B2 and -C. High levels of cdc25A and cdc25B2 were found in 35% and 39% of the tumors, respectively, and they were more frequently observed in aggressive than in indolent lymphomas. cdc25B1 and -B3 splice variants were detected in virtually all tumors, and no significant differences were found between high- and low-grade lymphomas. cdc25A and -B protein expression was also higher in aggressive than in indolent lymphomas. cdc25C expression was relatively low in virtually all cases. In conclusion, these findings suggest that cdc25A and -B2, but not cdc25B1, -B3 and -C, are over-expressed in a relatively large number of malignant lymphomas and may participate in the pathogenesis of aggressive variants.

Blotting, Western↗

PubMed2000

INK4a/ARF locus alterations in human non-Hodgkin's lymphomas mainly occur in tumors with wild-type p53 gene.

INK4a/ARF locus codes for two different proteins, p16(INK4a) and p14(ARF), involved in cell cycle regulation. p14(ARF) is considered an upstream regulator of p53 function. To determine the role of these genes in the pathogenesis of human non-Hodgkin's lymphomas we have analyzed exon 1beta, 1alpha, and 2 of the INK4a/ARF locus and p53 gene aberrations in 97 tumors previously characterized for p16(INK4a) alterations. p53 alterations were detected in four of 51 (8%) indolent lymphomas but in 15 of 46 (33%) aggressive tumors. Inactivation of p14(ARF) was always associated with p16(INK4a) alterations. Exon 1beta was concomitantly deleted with exon 1alpha and 2 in eight tumors. One additional lymphoblastic lymphoma showed deletion of exon 1alpha and 2 but retained exon 1beta. No mutations were detected in exon 1alpha and 1beta in any case. Two of the three mutations detected in exon 2 caused a nonsense mutation in the p16(INK4a) reading frame and a missense mutation in the ARF reading frame involving the nucleolar transport domain of the protein. The third mutation was a missense mutation in the p16(INK4a) reading frame, but it was outside the coding region of p14(ARF). Aggressive lymphomas with p14(ARF) inactivation and p53 wild type showed a significantly lower p53 protein expression than tumors with no alteration in any of these genes. In this series of tumors, inactivation of the INK4a/ARF locus mainly occurred in tumors with a wild-type p53 gene because only two lymphomas showed simultaneous aberrations in these genes. Tumors with concomitant alterations of p16(INK4a) and p14(ARF)/p53 genes seem to exhibit a worse clinical behavior than lymphomas with no alterations or isolated inactivation of any of these genes. These findings indicate that p14(ARF) genetic alterations occur in a subset of aggressive NHLs, but they are always associated with p16(INK4a) aberrations. Concomitant disruption of p16(INK4a) and p14(ARF)/p53 regulatory pathways may have a cooperative effect in the progression of these tumors.

Carrier Proteins↗

PubMed2000

Placental pathology in malaria: a histological, immunohistochemical, and quantitative study.

To characterize the histological changes in malarial placentas and their relationship with parity and maternal and cord parasitemias, we conducted a histological study on 1,179 placentas from Ifakara, Tanzania, an area with intense and perennial malaria transmission. Immunohistochemical and quantitative studies for CD45, fibrin, and villous area were performed in 60 cases. Four hundred fifteen placentas (35.2%) showed parasites (active infections); in 303 of them, parasites co-existed with pigment covered by fibrin (chronic infections), and in 112 only parasites were detected (acute infections). Four hundred seventy-five cases (40.3%) showed hemozoin deposition without parasites (past infections). Of women with parasitized placentas, 46.3% did not show parasites in the peripheral blood. Basal membrane thickening (P = .002), fibrinoid necrosis (P = .004), and prominence of syncytial knots (P = .031) were associated with active malarial infection. No quantitative differences for perivillous fibrin deposition or villous area were found. The most significant association with active malarial infection was intervillous infiltration by mononuclear inflammatory cells (P < .001). Chronic infections were associated with the most severe changes, particularly intervillous mononuclear inflammation (OR, 28.7; 95% CI = 16.0 to 51.5, P< .001). Past infections showed only minimal differences with noninfected placentas. Primiparas showed chronic infections more frequently than multiparas (52% v 15%, P < .001). They also showed significantly higher placental parasitemias and intervillous inflammatory infiltrate. In conclusion, placental histology is more sensitive than peripheral blood examination in detecting malarial infection during pregnancy. Most malarial infections recover during pregnancy, leaving few residual changes in the placenta. Intervillous inflammation is the most frequent finding associated with malaria and is especially severe in primiparas, suggesting that mechanisms other than immunosuppression are responsible for the high susceptibility in this group.

Female↗

PubMed2000

Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell ("sugar") tumor versus malignant melanoma.

A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.

Aged↗

PubMed2000

The Ljubljana classification: a practical strategy for the diagnosis of laryngeal precancerous lesions.

There is no internationally accepted classification of epithelial hyperplastic laryngeal lesions (EHLL). The majority of current classifications follow criteria similar to those commonly used for cervical epithelial lesions. However, the different etiology of laryngeal cancer and its particular clinical and histologic features necessitate a grading system more appropriate to this region. The Ljubljana classification of EHLL was devised in 1971 to cater to this requirement. Detailed criteria for histologic grading in this classification were formulated by a working group on EHLL of the European Society of Pathology in 1999. The system recognizes four grades: simple and abnormal hyperplasia are benign categories; atypical hyperplasia ("risky" epithelium) is potentially malignant, and carcinoma in situ actually malignant. The main features by which the proposed grading system differs from other classifications are: 1. the distinction between benign and potentially malignant lesions; 2. the positive separation of carcinoma in situ from atypical hyperplasia; 3. the lack of prognostic significance for any surface keratin layer. The eventual outcome of EHLL patients so graded justifies the proposal for separating the lesions into a benign group, showing malignant transformation in only 0.9% of cases, from a potentially malignant group showing malignant transformation in 11% of cases. For diagnostically difficult cases, supplementary techniques such as those using morphometry, immunohistochemical and molecular biology are advised to improve the accuracy of diagnosis and predictions of their biological behavior.

Carcinoma in Situ↗

PubMed1999

Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants.

Mantle cell lymphomas (MCLs) are characterized by 11q13 chromosomal translocations and cyclin D1 overexpression. The secondary genetic and molecular events involved in the progression of these tumors are not well known. In this study, we have analyzed 45 MCLs (32 typical and 13 blastoid variants) by comparative genomic hybridization (CGH). To identify the possible genes included in the abnormal chromosome regions, selected cases were analyzed for P53, P16(INK4a), RB, C-MYC, N-MYC, BCL2, BCL6, CDK4, and BMI-1 gene alterations. The most frequent imbalances detected by CGH were gains of chromosomes 3q (49%), 7p (27%), 8q (22%), 12q (20%), 18q (18%), and 9q34 (16%) and losses of chromosomes 13 (44%), 6q (27%), 1p (24%), 11q14-q23 (22%), 10p14-p15 (18%), 17p (16%), and 9p (16%). High-level DNA amplifications were identified in 11 different regions of the genome, predominantly in 3q27-q29 (13%), 18q23 (9%), and Xq28 (7%). The CGH analysis allowed the identification of regional consensus areas in most of the frequently involved chromosomes. Chromosome gains (P =. 02) and losses (P =.01) and DNA amplifications (P =.015) were significantly higher in blastoid variants. The significant differences between blastoid and typical tumors were gains of 3q, 7p, and 12q, and losses of 17p. CGH losses of 17p correlated with P53 gene deletions and mutations. Similarly, gains of 12q and high-level DNA amplifications of 10p12-p13 were associated with CDK4 and BMI-1 gene amplifications, respectively. One of 2 cases with 8q24 amplification showed C-MYC amplification by Southern blot. Alterations in 2p, 3q, 13, and 18q were not associated with N-MYC, BCL6, RB, or BCL2 alterations, respectively, suggesting that other genes may be the targets of these genetic abnormalities in MCLs. Increased number of gains (0 v 1-4 v >4 gains per case) (P =.002), gains of 3q (P =.02), gains of 12q (P =.03), and losses of 9p (P =. 003) were significantly associated with a shorter survival of the patients. These results indicate that an increased number of chromosome imbalances are associated with blastoid variants of MCLs and may have prognostic significance.

Blotting, Southern↗