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ABSTRACT: AIMS: Sentinel lymph node (SLN) biopsy is the current standard axillary approach for patients with clinically node-negative breast cancer. If the SLN is positive, is still also standard in most centres to proceed with a complete axillary dissection to predict the remaining nodes affectation, despite of SLN is the only positive lymph node in 50-68% of cases. If we could identify them, these patients could be spared a complete axillary dissection. METHODS: Elevated expression of specific matrix metalloproteases (MMPs) and their inhibitors (TIMPs) by stromal mononuclear inflammatory cells (MICs) of primary tumours is significantly associated with distant metastasis development in breast cancer. In the present study we first identified candidate MMPs/TIMPs associated with axillary metastasis in a preliminary group (n=50), and subsequently examined the potential of their expression in the SLN for predicting the status of the remaining nodes, in 105 patients with intraoperative SLN-assessment. RESULTS: MMP-1 expression by MICs from SLNs was significantly associated with metastatic spread to non-SLNs. Moreover, in all cases with negative MMP-1 expression by MICs from SLNs, the remaining non-SLNs were not affected (p<0.0001). Therefore, we demonstrate that MMP-1 expression by MICs from SLNs had 100% sensitivity, 100% negative-predictive value and 61.5% specificity to predict non-SLNs status. CONCLUSION: This is the first time that tumour spread to the remaining axillary nodes has been predicted from molecular features of the SLN(s). If confirmed in larger studies, patients could be spared the morbidity associated with an unnecessary complete lymphadenectomy.
European journal of cancer (Oxford, England: 1990) 10/2012; · 4.12 Impact Factor
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ABSTRACT: BACKGROUND: The aims of this study were to evaluate the microvascular density (MVD) at the center of breast carcinomas, its relationship with the expression of metalloproteases (MMPs) and their inhibitors (TIMPs), and its connection with the distant metastasis rate. METHODS: An immunohistochemical study of four MMPs and two TIMPs was performed on cancer specimens from 97 women with a histological confirmed diagnosis of early invasive breast cancer. RESULTS: Expressions of MMP-9 by cancerous cells, or MMP-11 and TIMP-2 by stromal cells, were all negative and significantly associated with MVD, whereas MMP-7 score values were positive and also significantly associated with MVD. However, positive expression of MMP-1 by mononuclear inflammatory cells was significantly associated with MVD. Multivariate analysis demonstrated a significant and inverse relationship between MVD and the occurrence of distant metastasis. CONCLUSIONS: Our data point out the clinical importance of low MVD at the tumor center as an independent prognostic factor of distant metastasis development in breast cancer.
International Journal of Clinical Oncology 06/2012; · 1.41 Impact Factor
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ABSTRACT: Matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) are of crucial importance in the degradation of the stromal connective tissue and basement membrane components. Study of the behavior of these components might help to predict the aggressiveness of tumors.
To evaluate the expression and clinical relevance of MMPs and TIMPs for patients with resectable colorectal carcinoma.
An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13, and 14, and TIMPs-1, 2 and 3. Determinations were performed in cancer specimens from 104 patients with resectable colorectal cancer. The minimum period of follow-up was 12.5 years for patients without recurrence. To identify specific groups of tumors with distinct expression profiles, the data were analyzed by unsupervised hierarchical cluster analysis.
Expression of MMP-11 by fibroblasts and MMP-13 by tumor cells were associated with poor prognosis. The dendrogram revealed first-order division of tumors into two distinct MMP/TIMP molecular profiles, designated group 1 (n = 50) and group 2 (n = 54). Group 2 was characterized by significantly higher expression of MMP-1, 11, and 13, and TIMP-3.
Our results emphasize the prognostic value of MMP-11 and 13 expression in colorectal cancer.
Digestive Diseases and Sciences 04/2012; 57(8):2063-71. · 2.12 Impact Factor
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ABSTRACT: There is evidence supporting the hypothesis that inflammation participates in providing conditions that lead to cancer. An unresolved inflammation due to any failure in the precise control of the immune response can continue to perturb the cellular microenvironment, thereby leading to alterations in cancer-related genes and posttranslational modification in crucial cellular proteins involved in the cell cycle, DNA repair and apoptosis. In addition, there are data indicating that inflammatory cells and immunomodulatory mediators present in the tumor microenvironment influence tumor progression and metastasis. Historically, tumor-infiltrating leukocytes have been considered to be manifestations of an intrinsic defence mechanism against developing tumors. However, increasing evidence indicates that leukocyte infiltration can promote tumor phenotypes, such as angiogenesis, growth and invasion. This may be due to inflammatory cells that probably can influence cancer promotion by secreting cytokines, growth factors, chemokines and proteases, which stimulate proliferation and invasiveness of cancer cells. Consequently, events and molecules implicated in this cross talk between the tumor microenvironment and inflammatory process may emerge as attractive targets in anticancer therapeutic interventions with significant clinical impact.
World journal of gastrointestinal surgery. 03/2012; 4(3):62-72.
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ABSTRACT: Myosin has raised an interest in cancer research because of its role in tumor progression. The aim of this study was to investigate the expression and clinical relevance of myosin in colorectal cancer (CC). Myosin was detected in CC tumors with recurrence using matrix-assisted laser desorption/ionization time-of-flight analysis. An immunohistochemical study was performed using tissue arrays and specific antibodies against myosin heavy chain. Determinations on cancer specimens from 91 patients with resectable CCs were performed. The minimum follow-up period was of 12.5 years for these patients without tumor recurrence. Western blot and real-time polymerase chain reaction analysis were also performed. Samples of carcinomas with recurrence showed an increased expression of myosin. Tumors with high myosin expression by tumor cell were significantly associated with higher probability of metastasis. Our results suggest that myosin expression in CCs is associated with tumor progression and metastasis development. Therefore, myosin tumor expression may contribute to an improved prognostic evaluation in patients with CC.
Annals of diagnostic pathology 03/2012; 16(4):260-6.
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ABSTRACT: Dysregulation of toll-like receptors (TLR) signaling can result in chronic inflammatory and over-exuberant repair responses. The aim of this study was to investigate the expression and clinical relevance of TLR in colorectal polyps.
The expression levels of six TLR were analyzed in 70 patients with different histological types of colorectal polyps, 38 of which developed colorectal carcinoma (CC). These analyses were performed by real-time polymerase chain reaction, western blot, and immunohistochemistry.
TLR9 expression was higher in hyperplastic or adenomatous polyps compared to other polyp types. Hyperplastic polyps also showed increased TLR7 levels compared to the other polyp types. TLR7 expression was lower in both hyperplastic and tubulovillous adenoma polyps from patients who developed CC. TLR9 expression was decreased in hyperplastic and villous polyps from patients who developed CC.
Our findings suggest a possible protective role of TLR expression against malignant transformation in the colorectal mucosa. TLR may represent a pathological marker of CC risk in colorectal polyps. The role of these factors in the pathology of colorectal polyps deserves further investigation.
Journal of Clinical Immunology 02/2012; 32(4):848-54. · 3.08 Impact Factor
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ABSTRACT: Inflammatory conditions may promote tumor progression and aggressiveness. In previous reports, we found a group of breast cancer tumors characterized by metalloprotease-11 (MMP-11) expression by intratumoral mononuclear inflammatory cells (MICs), which was associated with distant metastasis development. Thus, in the present study we evaluated the relationship between MMP-11 expression by MICs, distant metastasis development, and a wide panel of inflammatory factors in breast carcinoma. In an initial approach, we analyzed 65 factors associated with tumor progression and inflammation, in a tumor population classified in good or bad prognosis, based on MMP-11 expression by intratumoral MICs. The most differentially expressed factors were then analyzed in a wider tumor population classified according to MMP-11 expression by MICs and also according to metastasis development. These analyses were carried out by Real-time PCR. The results showed that of the 65 starting factors analyzed, those related with MMP-11 expression by MICs were: IL-1, -5, -6, -8, -17, -18, MMP-1, TIMP-1, ADAM-8, -10, -15, -23, ADAMTS-1, -2, -15, Annexin A2, IFNβ, Claudin-3, CCL-3, MyD88, IRAK-4 and NFκB. Of them, factors more differentially expressed between both groups of tumors were IL-1, IL-5, IL-6, IL-17, IFNβ and NFκB. Thereafter, we confirmed in the wider tumor population, that there is a higher expression of those factors in tumors infiltrated by MMP-11 positive MICs. Altogether these results indicate that tumors developing worse prognosis and identified by MMP-11 expression by intratumoral MICs, shows an up-regulation of inflammatory-related genes.
PLoS ONE 01/2012; 7(11):e49047. · 4.09 Impact Factor
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ABSTRACT: Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68(+)), T-cells (CD3(+)) and B-cells (CD20(+)) at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2). In addition, a high CD68/(CD3+CD20) ratio (>0.05) was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24), p<0.01). Therefore, CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker.
PLoS ONE 01/2012; 7(12):e52796. · 4.09 Impact Factor
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ABSTRACT: The aim of the present work was to perform a comparative study of stromal cell expressions of MMPs and TIMPs between benign and malignant prostate tissues.
An immunohistochemical study was performed using specific antibodies against metalloproteases (MMPs) -1, -2, -7, 9, 11, 13, 14 and their tissue inhibitors (TIMPs) -1, 2 and 3, on prostate specimens from 133 patients with clinical localized prostate carcinoma and from 50 patients with BPH.
Our results showed higher percentages of expressions of MMPs and TIMPs by fibroblasts or by mononuclear inflammatory cells (MICs) in prostate carcinomas compared to these cells in BPH. The detection of MMP-2 expression by stromal fibroblasts and/or MMP-2, 9 and TIMP-3 expression by stromal MICs was associated with a 100% of specificity for diagnoses of prostate cancer. We found that the combination of MMP-2 expression by fibroblasts and/or MMP-9 by MICs and/or TIMP-2 by MICs yielded a sensitivity of 47.4%.
Despite of a limited sensitivity (50%), the combination of MMP-TIMPs expression in stromal cells (MMP-2 by fibroblasts and TIMPs by MICs) in our study provided a specificity of 100% for prostate cancer diagnosis.
Journal of Cancer Research and Clinical Oncology 03/2011; 137(3):551-5. · 2.56 Impact Factor
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ABSTRACT: Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, and 9 in prostate cancer.
The expression levels of TLR3, TLR4, and TLR9 were analyzed on tumors from 133 patients with prostate cancer. The analyses were performed by immunohistochemistry on tissue arrays and real time-PCR.
Cancerous cells showed high expression levels of TLRs compared with controls. Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4, and TLR9. In addition, the tumors that showed high TLR3 or TLR9 expression levels were significantly associated with higher probability of biochemical recurrence.
TLR expression is associated with prostate cancer with recurrence and the role of TLR receptors in the biology of malignancy merits study. Therapeutic strategies to boost or block TLRs may be of interest.
Cancer Immunology and Immunotherapy 10/2010; 60(2):217-26. · 3.70 Impact Factor
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ABSTRACT: To investigate the possible clinical value of the expression of MMPs and their tissue inhibitors (TIMPs) by the different cellular types of the tumor scenario to predict biochemical recurrence in patients undergoing radical prostatectomy due clinically localized prostate cancer.
An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13 and 14 and TIMPs-1, 2 and 3 on cancer specimens from 133 patients with clinical localized prostate carcinoma.
Immunostaining for all the proteins studied was localized predominantly in tumor cells, but also in stromal cells in a significant percentage of prostate carcinomas, ranged from 20 to 50% for several proteins in fibroblast-like cells and in mononuclear inflammatory cells. Multivariate analysis according to a Cox model demonstrated that tumor stage (P < 0.0001) and Gleason grading (grades 7-10: 2.08 (1.1-3.9); P < 0.05) were significantly and independently associated with biochemical recurrence. Additionally, the expression of MMP-9 by fibroblast-like cells (P < 0.01) and MMP-13 by tumor cells (P < 0.05) were also variables significantly and independently associated with biochemical recurrence.
MMP-13 expression by tumor cells and MMP-9 by stromal fibroblast-like cells were independent factors of biochemical recurrence in prostate cancer.
World Journal of Urology 10/2010; 29(5):657-63. · 2.41 Impact Factor
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ABSTRACT: To investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in patients who develop local recurrence (LR) after mastectomy.
We analyzed the expressions of MMP-1, -2, -7, -9, -11, -13, -14, TIMP-1, -2, and -3, using immunohistochemical techniques, in primary tumors from patients without tumoral recurrence (n = 50), patients who developed distant metastasis (n = 50), and from patients who develop LRs (n = 25). LRs of the latter group were also analyzed for MMPs expression. All the patients underwent mastectomy.
Score values for all MMPs and TIMPs were significantly higher in primary tumors of patients with distant metastasis. Primary tumors from patients with LR have lower expressions of MMPs and TIMPs compared with those from patients who developed distant metastasis, and with patients without recurrence for some MMPs. Remarkably, however, primary tumors from patients with LR showed significantly higher percentage of TIMP-1 and 2 expression in stromal cells compared to primary tumors from patients with distant metastasis or primary tumors from patients without tumoral progression. Furthermore, LRs had significantly higher MMP-9 expression than their corresponding primary tumors.
Our data indicate differences in MMPs/TIMPs expression between primary tumors of patients with LRs and of those with distant metastasis, both after mastectomy for breast cancer.
Journal of Cancer Research and Clinical Oncology 07/2010; 136(7):1049-58. · 2.56 Impact Factor
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Luis O Gonzalez,
Sara Junquera,
Jose M del Casar,
Lucía González,
Laura Marín,
Salomé González-Reyes,
Alejandro Andicoechea,
Raquel González-Fernández,
José M González,
Román Pérez-Fernández, Francisco J Vizoso
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ABSTRACT: We assessed differences in the patterns of expression of matrix metalloproteases and their inhibitors (tissue inhibitors of metalloproteases) in ductal carcinoma in situ alone and admixed with invasive ductal carcinomas (n = 40), as well as in pure invasive ductal carcinomas (n = 40), immunohistochemically and using tissue arrays. The invasive ductal carcinoma components showed higher expression of matrix metalloprotease-9 and -13 than did the admixed ductal carcinoma in situ, whereas stromal fibroblasts of the invasive components showed higher expression of matrix metalloprotease-2, -7, -9, -13, and -14 and tissue inhibitor of metalloprotease-1 and -3 than did fibroblasts around the neoplastic ducts of the admixed ductal carcinoma in situ. Expression of matrix metalloprotease-14 and tissue inhibitor of metalloprotease-3 was significantly higher in the mononuclear inflammatory cells of the invasive components. By contrast, matrix metalloprotease-1 expression was significantly higher in stromal cells of the ductal carcinoma in situ admixed with invasive ductal carcinoma. The pure invasive ductal carcinomas had significantly higher expression of matrix metalloprotease-1, -9, -11, and -14 and tissue inhibitor of metalloprotease-1 and -3 than the invasive ductal carcinomas admixed with ductal carcinoma in situ. Our findings indicate a significant association of matrix metalloprotease expression by the periductal stromal cells of the ductal carcinoma in situ component of mixed tumors and the occurrence of distant metastasis. Our data suggest that the molecular matrix metalloprotease/tissue inhibitor of metalloprotease profile can contribute to better characterization of early breast carcinomas.
Human pathology 03/2010; 41(7):980-9. · 3.03 Impact Factor
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ABSTRACT: Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.
The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.
Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.
The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.
BMC Cancer 01/2010; 10:665. · 3.01 Impact Factor
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ABSTRACT: To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors.
Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2.
Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (<or= 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042).
Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer.
BMC Cancer 01/2010; 10:8. · 3.01 Impact Factor
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ABSTRACT: To analyze the expression and prognostic value of matrix metalloproteases and their tissue inhibitors in luminal A and basal-like breast carcinomas, an immunohistochemical study was performed on cancer specimens from 93 randomly selected patients with invasive primary ductal tumors of the breast (46 with and 47 without distant metastasis) and with luminal A (n = 48) (ER+, HER2-) or basal-like (HER2-, ER-, PgR-) (n = 45) lesions. Luminal B cases were too few to analyze. Specimens were also studied using tissue microarrays and specific antibodies against matrix metalloproteases 1, 2, 7, 9, 11, 13, and 14 and tissue inhibitors 1, 2, and 3. There were no significant differences in matrix metalloprotease or tissue inhibitor expression in the 2 phenotypes of tumors. In basal-like carcinomas, high scores for matrix metalloproteases 9 and 11 were significantly associated with a high distant metastasis rate. Likewise, data showed associations between matrix metalloprotease/tissue inhibitor expression by either stromal fibroblasts or mononuclear inflammatory cells and distant relapse-free survival in both tumor phenotypes. In addition, in infiltrating luminal A and basal-like tumors, we identified a prometastatic phenotype of mononuclear inflammatory cells, showing a high matrix metalloprotease/tissue inhibitor molecular profile. Expression of matrix metalloproteases and tissue inhibitors is related to the characteristics of breast tumor cells. As prognostic factors in breast carcinomas of both luminal A and basal-like phenotypes, our results point to the importance of the expression of matrix metalloproteases and tissue inhibitors by the stromal cells.
Human pathology 06/2009; 40(9):1224-33. · 3.03 Impact Factor
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ABSTRACT: Lymphatic and/or blood vessel tumoral invasion (LBVI) is a common histopathologic finding of gastric carcinomas, which could make it an additional cost efficient marker and help in the detection of patients at risk for recurrence.
The subjects of this study were 144 patients with primary gastric adenocarcinoma, who consecutively underwent surgery. LBVI was evaluated by H&E staining and complementary with immunohistochemical staining with anti-CD34. Intratumoral levels of EGFR were analyzed with a radioligand technique, whereas c-erbB-2 and tPA were determined by ELISA methods; pS2, cathepsin D and hyaluronic acid by immunoradiometric assays; and VEGFR-1 and -2 by immunohistochemical assays. The mean follow-up period for these patients was 33.1 months.
LBVI was present in 46 patients (31.9%). The presence of LBVI correlated significantly with tumor stage, lymph node involvement, surgical resectability, histological type and histological grade, being present in a higher percentage among II-IV tumor stage (P = 0.0001), poorly differentiated (P = 0.01), diffuse type (P = 0.009), R1-R2 (P = 0.002) and lymph node-positive (P = 0.005) tumors. In addition, statistical analysis demonstrated that LBVI was significantly associated with a poorer overall patients' survival in the univariate analysis (P = 0.0001) as well as in the multivariate analysis (P = 0.009). However, our results failed to show any significant relationship between LBVI and any of the intratumoral biological parameters studied.
LBVI provides additional useful information that could be applied to identify gastric cancer patients at risk for recurrence, who might be candidates for further adjuvant therapies.
Journal of Cancer Research and Clinical Oncology 03/2008; 134(2):153-61. · 2.56 Impact Factor
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Concepcion Ildefonso,
Julio Vazquez,
Oscar Guinea,
Alejandro Perez,
Amalia Fernandez,
Maria D Corte,
Sara Junquera,
Luis O Gonzalez,
Paz Pravia,
Manuel Garcia-Moran, Francisco J Vizoso
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ABSTRACT: To evaluate the clinical significance of the mammographic appearance of tumors in 411 patients with infiltrating ductal carcinoma of the breast.
Tumors were classified into five radiographic subgroups: spiculated mass (A-type), diffuse changes with or without suspicious microcalcifications (B-type), microcalcifications with a mass (C-type), circumscribed (D-type), and not visible (E-type). Intratumoral levels of estrogen (ER) and progesterone (PR) receptors, c-erbB-2, EGFR, pS2, cathepsin D and tPA, ploidy and S-phase fraction, were analysed in a significant number of cases.
A-type A radiographic pattern was detected in 234 patients (57%), B-type in 46 (11%), C-type in 46 (11%), D-type in 68 (17%), and E-type in 17 patients (4%). On the other hand, a total of 155 tumors (37.8%) showed microcalcifications. The percentage of tumors showing A-type pattern was more frequent in postmenopausal women, in well-differentiated tumors, and in those showing higher levels of ER, pS2 of tPA. However, B-type pattern was detected in a high percentage of premenopausal women and in those showing larger tumors, positive nodes, poor differentiation or high S-phase fraction. Cox multivariate analysis showed that B-type pattern and the absence of microcalcifications were factors significantly associated to high risk for relapse.
Our results suggest that the mammographic appearance of tumor may to provide useful clinical information in addition to classical prognostic factor in infiltrating ductal carcinoma of the breast.
European Journal of Obstetrics & Gynecology and Reproductive Biology 03/2008; 136(2):224-31. · 1.97 Impact Factor
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ABSTRACT: In the present study we analyze, in patients with breast cancer, the tumor expression of androgen receptors (AR), its relationship with clinicopathological characteristics and with the expression of several matrix metalloproteases (MMPs) and their inhibitors (TIMPs), as well as with prognosis.
An immunohistochemical study was performed using tissue microarrays and specific antibodies against AR, MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 2,800 determinations on tumor specimens from 111 patients with primary invasive ductal carcinoma of the breast (52 with axillary lymph node metastases and 59 without them) and controls were performed. Staining results were categorized using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically.
A total of 83 cases (74.8%) showed a positive immunostaining for AR, but with a wide variation in the staining score values. There were no significant associations between the total immunostaining scores for AR and any clinicopathological parameters. However, score values for MMP-1, -7 and -13, were significantly higher in AR-positive tumors than in AR-negative tumors. Likewise, when we considered the cellular type expressing each factor, we found that AR-positive tumors had a higher percentage of cases positive for MMP-1, -7, -11, and TIMP-2 in their malignant cells, as well as for MMP-1 in intratumoral fibroblasts. On the other hand, multivariate analysis demonstrated that patients with AR-positive tumors have a significant longer overall survival than those with AR-negative breast carcinomas (p = 0.03).
Our results confirm that AR are commonly expressed in breast cancer, and are correlated with the expression of some MMPs and TIMP-2. Although we found a specific value of AR expression to be a prognostic indicator in breast cancer, the functional role of AR in these neoplasms is still unclear and further data are needed in order to clarify their biological signification in breast cancer.
BMC Cancer 02/2008; 8:149. · 3.01 Impact Factor
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Diego Pidal,
M Teresa Sánchez Vidal,
Juan Carlos Rodríguez,
M Daniela Corte,
Paz Pravia,
Oscar Guinea,
Iván Pidal,
Miguel Bongera,
Dámaso Escribano,
Luis O González,
M Cruz Díez,
Rafael Venta, Francisco J Vizoso
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ABSTRACT: To assess whether breast arterial calcifications (BAC) are associated with altered serum markers of cardiovascular risk, mammograms and records from 1759 women (age range: 45-65 years) screened for breast cancer were revised. One hundred and forty seven (8.36%) women showed BAC. A total of 136 women with BAC and controls (mean age: 57 and 55 years, respectively) accepted entering the study. There were no significant differences in serum levels of urea, glucose, uric acid, creatinine, total cholesterol, HDL-C, LDL-C, folic acid, vitamin B(12), TSH or cysteine, between both groups of patients. However, women with BAC showed higher serum levels of triglycerides (p=0.006), homocysteine (p=0.002) and hs-CRP (p=0.003) than women without BAC. Likewise, we found a significantly higher percentage of cases with an elevated LDL-C/HDL-C ratio (coronary risk index >2) amongst women with BAC than in women without BAC (56.7 and 38.2%, respectively; p=0.04). Our results indicate that the finding of BAC identify women showing altered serum markers of cardiovascular risk.
European journal of radiology 11/2007; 69(1):87-92. · 2.65 Impact Factor
