Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers.
; Hachana, Mohamed Ridha ; et al
in Human Pathology (2012)
DNA methyltransferase 1, 3a, and 3b affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers. The current study was designed to analyze ... [more ▼]
DNA methyltransferase 1, 3a, and 3b affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers. The current study was designed to analyze DNA methyltransferase expression by immunohistochemistry in a series of 94 Tunisian sporadic breast carcinomas. Results were correlated to clinicopathologic parameters and promoter methylation status of 8 tumor suppressor genes (BRCA1, BRCA2, RASSFA1, TIMP3, CDH1, P16, RARβ2, and DAPK). Overexpression of DNA methyltransferase 1, 3a, and 3b was detected in 46.8%, 32%, and 44.7% of cases, respectively. A significant correlation was found between DNA methyltransferase 1 overexpression and Scarff-Bloom-Richardson histologic grade III (P = .01). DNA methyltransferase 3a overexpression was significantly associated with menopausal status (P = .01), Scarff-Bloom-Richardson histologic grade III (P = .0001), estrogen (P = .04) and progesterone (P = .007) receptor negativity, and HER2 overexpression (P = .004). However, DNA methyltransferase 3a overexpression was found less frequently in the luminal A intrinsic breast cancer subtype (9.7%) than in luminal B (53%), HER2 (41%), and triple-negative (50%) subtypes (P = .001). DNA methyltransferase 3b overexpression shows significant correlation with promoter hypermethylation of BRCA1 (P = .03) and RASSFA1 (P = .04) and with the hypermethylator phenotype (more than 4 methylated genes, P = .01). These data suggest that overexpression of various DNA methyltransferases might represent a critical event responsible for the epigenetic inactivation of multiple tumor suppressor genes, leading to the development of aggressive forms of sporadic breast cancer. [less ▲]Detailed reference viewed: 44 (2 ULg)
Primary mucosa-associated lymphoid tissue lymphoma of the gallbladder: report of a case harboring API2/MALT1 gene fusion.
Bisig, Bettina ; ; et al
in Human Pathology (2009), 40(10), 1504-9
The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a ... [more ▼]
The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a case of mucosa-associated lymphoid tissue lymphoma of the gallbladder with genetic characterization. This lymphoma, diagnosed in a 75-year-old woman who underwent cholecystectomy for suspected acute cholecystitis, presented as diffuse thickening of the gallbladder wall. The morphology was typical of mucosa-associated lymphoid tissue lymphoma, and by immunophenotype, the tumor cells were CD20+ CD5- CD10- CD23- CD43- BCL6- BCL2+ IgM+ IgD- lambda+, with moderate nuclear expression of BCL10. Interphase fluorescence in situ hybridization analysis on paraffin sections, using a fusion probe for API2/MALT1, demonstrated 2 fusion signals in most nuclei, bringing the first documentation of a t(11;18)(q21;q21) in this exceptional primary disease location. [less ▲]Detailed reference viewed: 41 (9 ULg)
Inflammatory pseudotumors of the central nervous system: Report of 3 cases and a literature review
; ; Ramaekers, Vincent et al
in Human Pathology (2003), 34(3), 253-262
Inflammatory pseudotumors (IPs), mostly benign lesions characterized by fibrotic ground tissue and polyclonal mononuclear infiltrate, may affect all organ systems. IPs originating in the central nervous ... [more ▼]
Inflammatory pseudotumors (IPs), mostly benign lesions characterized by fibrotic ground tissue and polyclonal mononuclear infiltrate, may affect all organ systems. IPs originating in the central nervous system (IP-CNS) are very rare, and their distinct histopathologic features are poorly characterized. Three otherwise healthy patients (age 8, 15, and 17 years) presented with focal neurologic symptoms (seizures, n = 2; headaches, n = 1), corresponding to a left temporal, left occipital, and left frontal IP, respectively, extending from meningeal structures into brain tissue. After resection, no recurrence was observed in patient 1 during 5 years of follow-up, whereas patient 2 developed a rapidly progressive local recurrence and a second intracerebral lesion despite antiviral, immunosuppressive, antibiotic, and radiation therapy. In patient 3, who also showed local recurrences, sequential histopathologic investigations revealed transformation to a semimalignant fibrohistiocytic tumor. In this patient, anaplastic lymphoma kinase (ALK) expression was also positive, whereas it was negative in patient 1. A detailed literature analysis confirmed that most IP-CNS arise from dural/meningeal structures (n = 34). Intraparenchymatous (n = 7), mixed intraparenchymatous/meningeal (n = 4), and intraventricular lesions (n = 7) or IP extending per continuitatem from intracerebral to extracerebral sites (n = 5) were rare. The recurrence rate was 40% within 2 years in general. It was increased after incomplete resection and in female patients (multivariate Cox regression model, P < 0.02). Although rare, IP-CNS are important differential diagnoses among tumor-like intracranial lesions. Their potential risk of malignant transformation and high risk of recurrence necessitate close follow-up, especially when resection is incomplete. Prospective multicenter trials are needed to optimize classification and treatment of this rare inflammatory lesion. Copyright 2003, Elsevier Inc. All rights reserved. [less ▲]Detailed reference viewed: 9 (0 ULg)
Predictive factors in locally advanced rectal cancer treated with preoperative hyperfractionated and accelerated radiotherapy.
; ; et al
in Human Pathology (2003), 34(6), 541-548
This study examines the prognostic significance of pathologic factors in patients with primary locally advanced rectal cancer treated prospectively with preoperative radiotherapy. From 1992 to 1998, 104 ... [more ▼]
This study examines the prognostic significance of pathologic factors in patients with primary locally advanced rectal cancer treated prospectively with preoperative radiotherapy. From 1992 to 1998, 104 patients with rectal cancer of grades T3 or T4 and any N underwent preoperative radiotherapy followed by surgical resection. Survival curves were estimated according to the Kaplan-Meier method. Correlation of outcome with clinicopathologic variables (pathologic tumor and lymph node staging, histology, radial resection margin [RRM], clearance, vessel involvement, and tumor regression grade [TRG], quantitated in 5 grades) was evaluated using the Cox proportional hazards model. None of the patients achieved a histologically confirmed complete pathologic response, but 79% of the patients showed partial tumor regression (TRG2–4) and 21% did not show any tumor regression (TRG5). Among the tumors, 22% were of a mucinous type. The RRM was free of tumor in 76% of the surgical specimens. The median clearance was 2 mm. Vascular invasion was present in 37 cases (36%). In the univariate analysis, lymph node metastases, absence of tumor regression, positive RRM, and vascular invasion were correlated with adverse overall survival and diseasefree survival; absence of tumor regression, positive RRM, and clearance <2 mm were correlated with local recurrences; and advanced pT stage was correlated only with disease-free survival. However, in the multivariate analysis, only lymph node metastases and RRM were independent prognostic factors for overall survival and disease-free survival, and clearance <2 mm was an independent prognostic factor for local control. Pathologic parameters remain strong determinants of local recurrence and survival in locally advanced rectal cancer, treated preoperatively with hyperfractionated and accelerated radiotherapy. We show that patients with advanced pT, positive lymph nodes, vascular invasion, positive RRM, clearance <2 mm, or absence of tumor regression are known to have poor clinical outcome. HUM PATHOL 34:541-548. © 2003 Elsevier Inc. All rights reserved. Abbreviations: , computed tomography; DFS, disease-free survival; HART, hyperfractionated accelerated radiotherapy; OS, overall survival; RRM, radial resection margin; TRG, tumor regression grade. [less ▲]Detailed reference viewed: 24 (4 ULg)
Expression of the 67-Kd Laminin Receptor, Galectin-1, and Galectin-3 in Advanced Human Uterine Adenocarcinoma
; ; et al
in Human Pathology (1996), 27(11), 1185-91
Alterations of tumor cell interactions with laminin, a basement membrane glycoprotein, are consistent features of the invasive and metastatic phenotype. Qualitative and quantitative changes in the ... [more ▼]
Alterations of tumor cell interactions with laminin, a basement membrane glycoprotein, are consistent features of the invasive and metastatic phenotype. Qualitative and quantitative changes in the expression of cell surface laminin-binding proteins have been correlated with the ability of cancer cells to cross basement membranes during the metastatic cascade. Such phenotypic modifications are usually associated with poor prognosis. In this study, the authors examined the possibility that expression of three laminin-binding proteins, the 67-kD laminin receptor (67LR), galectin-1, and galectin-3, is altered in human endometrial cancer in a fashion similar to that reported in other carcinomas, such as breast, colon, and ovarian cancer. Twenty advanced uterine adenocarcinomas were analyzed for expression of these three molecules using immunoperoxidase staining and specific antibodies. The authors found a significant increase in the expression of the 67LR and galectin-1 in cancer cells compared with normal adjacent endometrium (P = .0004 and .0022, respectively). As observed in other carcinomas, a significant down-regulation of galectin-3 expression was found in endometrial cancer cells compared with normal mucosa (P = .02). In the galectin-3 positive tumors, galectin-3 was detected in the cytoplasm and/or nucleus of cancer cells. Interestingly, tumors in which galectin-3 was detected only in the cytoplasm were characterized by deeper invasion of the myometrium than lesions where galectin-3 was found both in nucleus and cytoplasm (P = .02). This study shows an alteration of nonintegrin laminin-binding protein expression in advanced human endometrial cancer. Further studies on larger populations should determine the prognostic value of the detection of these laminin-binding proteins in endometrial carcinoma. Inverse modulation of the 67LR and galectin-3 appears to be a phenotypical feature of invasive carcinoma. [less ▲]Detailed reference viewed: 20 (1 ULg)
Expression of the monomeric 67-kd laminin-binding protein in human lymphomas as defined by MLuC5 monoclonal antibody and paraffin section immunohistochemistry.
; ; et al
in Human Pathology (1995), 26(5), 541-6
Interactions between cancer cells and laminin, a major component of basement membranes, are mediated through a large variety of cell surface proteins designated as laminin receptors. Among the above ... [more ▼]
Interactions between cancer cells and laminin, a major component of basement membranes, are mediated through a large variety of cell surface proteins designated as laminin receptors. Among the above proteins, a 67-kd monomeric high affinity laminin receptor (67 LR) has long been suspected to be involved in tumor progression. In this study we wished to establish whether the 67 LR molecule is detectable on tumor cells of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHLs), to define its pattern of expression, and to assess the potential utility of 67 LR in differentiating these pathological entities. Morphological and immunohistological studies were performed on 85 specimens of HD and a series of 334 NHL specimens, including anaplastic large cell (ALC) (CD30-positive) lymphomas (73 specimens). For immunohistochemical assessment of the 67 LR we used the monoclonal antibody (MoAb) MLuC5 directed against the 67-kd laminin receptor on paraffin-embedded sections. Reed-Sternberg cells reacted with MLuC5 MoAb in four of 85 (4.7%) HD specimens. Among the NHL specimens, a MLuC5-positive reaction was expressed in 3.3% of B-cell lymphomas. They all belonged to the high grade subtypes. On the other hand, a MLuC5-positive reaction was detected in none of the T-cell lymphomas tested. In contrast to the results obtained with the other NHLs, in 30.2% of ALC (CD30-positive) lymphoma specimens, tumor cells reacted with MLuC5 MoAb. MLuC5-expressing ALC (CD30-positive) lymphoma cells were of either T-cell (six of 17 specimens), B-cell (three of 25 specimens), or undetermined phenotype (10 of 31 specimens). Our investigation has shown that 67 LR as shown by MLuC5 MoAb is detectable only in neoplastic cells of a fraction of ALC (CD30-positive) lymphomas and small subsets of B-cell high grade NHLs and HD. The restricted expression of the 67 LR molecule to ALC (CD30-positive) lymphomas provides a potential tool for the phenotypic separation of this pathological entity from HD and other lymphomas. Whether the detection of the 67 LR expression in these lymphoma subsets may be related to the aggressiveness of the disease remains to be ascertained. [less ▲]Detailed reference viewed: 5 (0 ULg)
Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus.
; Foidart, Jean-Michel ; et al
in Human Pathology (1985), 16(5), 477-84
The diagnosis of light chain deposition nephropathy is based on the immunohistochemical demonstration of monoclonal light chain deposits within connective tissue matrix and on the presence at the ... [more ▼]
The diagnosis of light chain deposition nephropathy is based on the immunohistochemical demonstration of monoclonal light chain deposits within connective tissue matrix and on the presence at the ultrastructural level of electron-dense granular deposits along glomerular and tubular basement membranes. A nodular glomerulopathy characterized by amorphous periodic acid-Schiff-positive and argyrophilic widened mesangium and nodules is described in three patients with light chain deposition nephropathy. Light microscopic examination did not allow discrimination between the glomerular changes found in these specimens and the nodular glomerulosclerosis described in four patients with well-documented diabetes mellitus. Electron microscopic examination revealed microtubular fibrils 10 to 12 nm thick in mesangial areas in both groups. Such microfibrils could be glycoproteins. Immunofluorescence localization of matrix proteins, by staining with affinity-purified antibodies to types I, III, IV, and V (A, B) collagens, fibronectin, laminin, and heparan sulfate-containing proteoglycans, showed similar distributions in the two conditions. The mechanism of this abnormal accumulation of mesangial and glomerular basement membrane matrix proteins in two different conditions remains unknown. [less ▲]Detailed reference viewed: 3 (0 ULg)