Cristina Riva

Università degli Studi dell'Insubria, Varese, Lombardy, Italy

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Publications (17)54.92 Total impact

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    ABSTRACT: Abstract Metastases to the pituitary occur more frequently in patients with widespread cancer and mainly involve the posterior lobe. A few cases of metastatic carcinoma to a pituitary adenoma have been described so far. Here, the authors present an additional case of a clear cell renal cell carcinoma (CCRCC) metastatic to a FSH/LH/α-subunit pituitary adenoma and systematically review the literature. Immunohistochemistry and electron microscopy were performed to characterize both neoplastic components at the morphological level. Moreover, it was hypothesized that expression of VEGF and of the corresponding receptor VEGFR1 could be implicated in the development of the carcinomatous metastasis within the adenoma.
    Ultrastructural Pathology 07/2014; · 0.98 Impact Factor
  • Endocrine Pathology 04/2014; · 1.60 Impact Factor
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    ABSTRACT: We report a rare case of an ovarian mucinous cystadenoma in which there were peculiar neuroendocrine micronests composed of gastrin-immunoreactive cells. There was no clinical evidence of hypergastrinemia. The mucinous component of the neoplasm was represented by columnar cells mostly expressing a gastric phenotype with MUC5AC and claudin 18 positivity, which was consistent with the presence of interspersed gastrin cells. The tumoral stroma displayed areas of luteinization with cells intensely positive for α-inhibin, MART-1 and calretinin.
    Pathology - Research and Practice 07/2013; · 1.21 Impact Factor
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    ABSTRACT: In recent years, the role played by the stromal microenvironment has been given growing attention in order to achieve a full understanding of cancer initiation and progression. Because cancer is a tissue-based disease, the integrity of tissue architecture is a major constraint toward cancer growth. Indeed, a large contribution of the natural resistance to cancer stems from stromal microenvironment components, the dysregulation of which can facilitate cancer occurrence. For instance, recent experimental evidence has highlighted the involvement of stromal cells in ovarian carcinogenesis, as epitomized by ovarian xenografts obtained by a double KO of the murine Dicer and Pten genes. Likewise, we reported the role of an ancient extracellular RNase, called Ribonuclease T2 (RNASET2), within the ovarian stromal microenvironment. Indeed, hyperexpression of RNASET2 is able to control tumorigenesis by recruiting macrophages (mostly of the anticancer M1 subtype) at the tumor sites. We present biological data obtained by RNASET2 silencing in the poorly tumorigenetic and highly RNASET2-expressing human OVCAR3 cell line. RNASET2 knockdown was shown to stimulate in vivo tumor growth early after microinjection of OVCAR3 cells in nude mice. Moreover, we have investigated by molecular profiling the in vivo expression signature of human and mouse cell xenografts and disclosed the activation of pathways related to activation of the innate immune response and modulation of ECM components. Finally, we provide evidence for a role of RNASET2 in triggering an in vitro chemotactic response in macrophages. These results further highlight the critical role played by the microenvironment in RNASET2-mediated ovarian tumor suppression, which could eventually contribute to better clarify the pathogenesis of this disease.
    Proceedings of the National Academy of Sciences 04/2013; · 9.81 Impact Factor
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    ABSTRACT: A recent body of evidence indicates an active role for stromal (mis)-regulation in the progression of neoplasias. Within this conceptual framework, genes belonging to the growing but still poorly characterized class of tumor antagonizing/malignancy suppressor genes (TAG/MSG) seem to play a crucial role in the regulation of the cross-talk between stromal and epithelial cells by controlling malignant growth in vivo without affecting any cancer-related phenotype in vitro. Here, we have functionally characterized the human RNASET2 gene, which encodes the first human member of the widespread Rh/T2/S family of extracellular RNases and was recently found to be down-regulated at the transcript level in several primary ovarian tumors or cell lines and in melanoma cell lines. Although we could not detect any activity for RNASET2 in several functional in vitro assays, a remarkable control of ovarian tumorigenesis could be detected in vivo. Moreover, the control of ovarian tumorigenesis mediated by this unique tumor suppressor gene occurs through modification of the cellular microenvironment and the induction of immunocompetent cells of the monocyte/macrophage lineage. Taken together, the data presented in this work strongly indicate RNASET2 as a previously unexplored member of the growing family of tumor-antagonizing genes.
    Proceedings of the National Academy of Sciences 01/2011; 108(3):1104-9. · 9.81 Impact Factor
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    ABSTRACT: The estrogen receptor (ER)/progesterone receptor (PR)-negative breast carcinomas (BCs) encompass three molecular subtypes: one with human epidermal growth factor receptor 2 (HER) overexpression, one normal like, and the triple negative. The androgen receptor (AR) is expressed in 70-90% of invasive BCs. The aim of our study is to detect the expression of AR in a series of ER/PR-negative BCs to ascertain if there is clinical significance in relation to BC molecular subtypes. A immunohistochemical study for all receptors and cytokeratin expression was performed in 232 cases of ER/PR-negative BCs. According to cytokeratin expression, BCs were classified into two groups: luminal-type BCs (44.2%) and basal-like-type BCs (55.8%). According to the expression of HER2, 59.3% were triple-negative BCs (when ER, PR, and HER2 were negative) and 40.7% were HER2-positive BCs. AR expression was observed in 128 tumors (56.6%). One hundred and ten cases (48.8%) had >10% and 18 (7.8%) had <10% of positively stained cells. AR immunoreactivity was found in 31.2% basal-like BCs, while in the luminal group 71.1% of cases were positive, showing highly significant correlation (p < 10⁻⁸). Regarding HER2 status, 76.7% of HER2-positive BC cases were AR positive compared with only 30.4% of triple-negative BC types, showing a strong statistically significant correlation. In conclusion, we show that AR is frequently expressed in ER/PR-negative BCs and that expression of HER2 and AR is highly correlated (p < 0.005). Our results point out the role of AR and HER2 in the pathogenesis of BCs and suggest the potential role of AR in clinical management of ER/PR-negative BCs.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2010; 457(4):467-76. · 2.68 Impact Factor
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    ABSTRACT: Increased activity of Sp family of transcription factors is a frequent and critical event in cancer development and progression. Genes governing tumor growth, invasion and angiogenesis are regulated by Sp factors, like Sp1, Sp3 or Sp4, and are frequently over-expressed in tumors. Targeting Sp factors has been explored as a therapeutic approach. Mithramycin (MTM) is a natural antibiotic that binds DNA and inhibit Sp1-dependent transcription. New analogues, named MTM-SDK and MTM-SK, were recently obtained by genetic engineering of the MTM biosynthetic pathway and have demonstrated improved transcriptional and antiproliferative activity in ovarian cancer cell lines in vitro. In the present study we evaluated the activity of the new compounds in human ovarian cancer xenografts. Expression of Sp1 and target proteins in ovarian cancer specimens and tumor xenografts was assessed by immunohistochemistry. Drug-induced silencing of Sp1-regulated genes in cells and tumor xenograft samples was assessed by quantitative RT-PCR. Toxicity and antitumor activity of the compounds were investigated in healthy and tumor-bearing immunocompromised mice, respectively. Expression of Sp1 was frequently increased in human epithelial ovarian cancers. MTM-SDK and MTM-SK acted as potent inhibitors of Sp1-dependent transcription both in vitro and in tumor xenografts. Both compounds were well tolerated even after prolonged administration and delayed growth of ovarian tumor xenografts. MTM-SDK was particularly effective against orthotopic tumors leading to a significant increase of survival and delay of tumor progression. MTM-SDK and MTM-SK show relevant activity in vivo and represent interesting candidates for treatment of ovarian cancers.
    Gynecologic Oncology 05/2010; 118(2):182-8. · 3.93 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor. In addition to its canonical role in lipid and glucose metabolism, PPAR-gamma controls cell proliferation, death, and differentiation in several tissues. Here we have examined the expression of PPAR-gamma in ovarian tumors and the cellular and molecular consequences of its activation in ovarian cancer cells. PPAR-gamma was expressed in a large number of epithelial ovarian tumors and cell lines. The PPAR-gamma ligand ciglitazone inhibited the growth and clonogenic survival of ovarian cancer cells, inducing cell cycle arrest and cell death. Growth inhibition by ciglitazone was reversed by the PPAR-gamma antagonist GW9662, indicating the involvement of PPAR-gamma-dependent mechanisms. Microarray-based gene profiling revealed complex changes in the transcriptional program of ovarian cancer cells on treatment with ciglitazone and identified multiple pathways that may contribute to PPAR-gamma ligands' antitumor activity. Genes upregulated by ciglitazone were predominantly associated with metabolic, differentiation, and tumor-suppressor pathways, whereas downregulated genes were involved in cell proliferation, cell cycle, cell organization, and steroid biosynthesis. Collectively, our data indicate that PPAR-gamma activation by selective agonists is a valid strategy for ovarian cancer therapy and prevention, and should be tested alone and in combination with other anticancer drugs.
    Neoplasia (New York, N.Y.) 11/2006; 8(10):851-61. · 5.48 Impact Factor
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    ABSTRACT: One of the most controversial issues in breast pathology is whether lobular neoplasia (LN) is a risk factor or a precursor lesion of invasive lobular carcinoma (ILC). This is consequent to the fact that no conclusive data on the biology of LN exist. Molecular studies of LN and ILC are scanty, variable, and not consistent. Clonality of 12 cases of LN and ILC present simultaneously in the same block has been studied. Cells from both lesions were obtained by microdissection and were studied for mitochondrial DNA (mtDNA), D-loop sequencing, and neighbor-joining trees. Eight of the same cases were studied with comparative genomic hybridization (CGH) array to have additional data consistent with mtDNA. In all cases, loss of heterozygosity was studied for D16S496,locus 16q22.1 related to e-cadherin. It appears that no fewer than eight cases were genetically very similar (clonal) with mtDNA. Seven of these cases appeared also clonal with CGH array. It is concluded that in the present series, LN and ILC are genetically related lesions in the majority of cases and that LN might be the precursor of ILC.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2006; 449(1):14-23. · 2.68 Impact Factor
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    ABSTRACT: The methylation status of hMLH1, CDKN2A, and MGMT was investigated in a panel of synchronous cancers of the ovary and endometrium, fulfilling the clinicopathologic criteria for independent primary tumors to define the possible role of epigenetic mechanisms in the development of these cancers. Bisulfite-converted DNA from 31 tumors (13 endometrial and 18 ovarian carcinomas) and from matched normal tissue of 13 patients was analyzed by a methylation-specific PCR assay at the CpG-rich 5' regions of all three genes. In all tumors, we also investigated the presence of microsatellite instability and hMLH1 immunohistochemical expression in relation to hMLH1 hypermethylation status. Methylation of hMLH1, CDKN2A, and MGMT was detected in 39%, 41%, and 48% of endometrial and ovarian tumors, respectively. hMLH1 hypermethylation was observed in all tumors of five patients, and it was invariably associated with loss of hMLH1 protein and presence of microsatellite instability. CDKN2A and MGMT methylation was randomly detected among both endometrial (45% and 24% of cases, respectively) and ovarian carcinomas (39% and 39% of cases, respectively). Concordant methylation at two or three genes was observed in 35% of cases. Epigenetic inactivation of hMLH1, CDKN2A, and MGMT may be a common and early event in the development of synchronous primary endometrial and ovarian carcinomas and may qualify as a marker of a field cancerization encompassing the ovary and endometrium. Detection of MGMT hypermethylation may be useful to define a set of gynecologic malignancies with a specific sensitivity to alkylating chemotherapy.
    Clinical Cancer Research 07/2006; 12(11 Pt 1):3329-36. · 7.84 Impact Factor
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    ABSTRACT: Androgens and androgen receptors (AR) are involved in the pathogenesis of breast cancer. Epidemiological studies have shown a significant association between the risk of breast cancer and androgens. However, the functional role and clinical value of AR expression in breast carcinoma have still not been clearly defined. The present study was set up to investigate the prevalence of ARs in a series of consecutive invasive breast carcinomas (IBCs) and to evaluate the patterns of AR phenotypes in a series of selected invasive lobular carcinomas (ILCs). Among the 250 consecutive IBCs (consisting of 212 ductal and 38 lobular neoplasms), AR immunoreactivity was observed in 151/250 (60.4%) cases, being expressed in 118/212 (56%) ductal and 33/38 (87%) lobular carcinomas (a statistically significant difference, chi2=11.82). AR expression was frequently associated with ER (65.2%, chi2=14.33) and PR positivity (66.9%, chi2=7.36). Most AR positive cases showed a low proliferative index (63.7%) and a low or intermediate histological grade (G1-G2, 63.9%). Among the 80 selected ILCs, AR expression was observed in 64/80 (80%) cases. Our results confirm that ARs are expressed in most breast cancers. Moreover, we demonstrated that AR positivity is particularly marked in lobular neoplasms. In addition, AR positive carcinomas are frequently characterized by a low or intermediate grade, a low proliferative index and ER and/or PR co-expression.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2005; 447(4):695-700. · 2.68 Impact Factor
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    ABSTRACT: In this report we present the characterization of ovarian neoplasms including benign tumors, borderline tumors, and invasive carcinomas in order to assess whether a sharing of cytogenetic abnormalities is present in all three types of tumors. A cohort of 114 newly diagnosed and untreated ovarian epithelial tumors were analyzed by cytogenetic and molecular cytogenetic approaches with probes specific for chromosome 6. Three groups of chromosome abnormalities were identified: the first group included abnormalities common to all tumor classes (losses of chromosomes 6, 8, 10, 11, 15, 16, 17, 18, 19, 20, 21, 22, and X; gains of chromosomes 1, 3, 5, and 12; 6q24 approximately qter deletions); the second group presented specific abnormalities present in malignant but not in benign tumors (losses of chromosomes 2, 7, 13, and 14; gains of chromosome 4 and chromosome markers); and the last group included abnormalities unique to invasive carcinomas (loss of chromosome 4; gains of chromosomes 2, 7, 8, 9, 10, 16, 17, 18, 19, 20, and 21; 6q16 approximately q24 deletions; rearrangements of 3p, 3q, 13q, and 21q regions). The presence of shared chromosomal alterations in all three types of ovarian neoplasms investigated in this report seems therefore to suggest a progression model for these types of tumors.
    Cancer Genetics and Cytogenetics 11/2003; 146(2):145-53. · 1.93 Impact Factor
  • Cancer Genetics and Cytogenetics 10/1996; 91(2):133-133. · 1.93 Impact Factor
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    ABSTRACT: Forty-two duodenal and 3 upper jejunum tumors from 44 patients were investigated. All tumors were tested immunohistochemically for gastroenteropancreatic hormones and general endocrine cell markers. Twenty-eight of the 45 tumors (62%) proved to be gastrin cell tumors, with (12 cases) or without (16 cases) associated Zollinger-Ellison syndrome. Zollinger-Ellison syndrome was part of type 1 multiple endocrine neoplasia syndrome in 3 cases. Twenty-three of the 28 gastrin cell tumors (82%) were from proximal duodenum, 2 were from the second part of the duodenum, and 3 were from the upper jejunum. Seven cases were somatostatin cell tumors, 6 of which were from the ampullary region; 5 cases were associated with biliary tract disease and 2 with associated cutaneous neurofibromatosis. Four ganglioneuromatous paragangliomas, from the ampullary region or nearby duodenum, showed somatostatin cells, coupled with pancreatic polypeptide cells in 2 cases. Two serotonin-producing argentaffin carcinoids were also identified. In addition to the main cell type, 30 tumors showed one or more, usually minor, cell populations producing somatostatin, serotonin, cholecystokinin, pancreatic polypeptide, insulin, neurotensin, or the alpha chain of human chorionic gonadotropin. Only 3 tumors lacked hormone immunoreactivity. Some correlation has been noted between histological structure and hormone content of tumor cells, with prevalence of broad gyriform trabeculae and vascular pseudorosettes among gastrin cell tumors, tubuloacinar patterns among somatostatin cell tumors, thin parallel trabeculae among PP cell growths, and a solid nest pattern among argentaffin carcinoids. Deep infiltration of the intestinal wall was observed in 22 tumors, 6 of which also had metastases to local lymph nodes. All metastatic cases were among ZES tumors or ampullary somatostatin cell tumors. Ganglioneuromatous paragangliomas and nonfunctioning gastrin cell tumors had essentially benign behavior, even when involving deep strata of the intestinal wall. Post operative follow-up study of 36 cases, including all metastatic tumors, showed no evidence of tumor-related death or progressive tumor disease.
    Endocrine Pathology 01/1991; 2(2):92-110. · 1.60 Impact Factor
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    ABSTRACT: Fourteen cases of intestinal-type adenocarcinomas (IADC) of the nasal cavity and paranasal sinuses were studied at the Regional Hospital of Varese during the period from 1973 to 1988. They were 13 males and 1 female, mean age 57.5 years; the five year survival was 25% and tumors were preferentially located in the ethmoidal sinus. Morphological study and the use of monoclonal and polyclonal antibodies made it possible to define the structural features of IADC and to detect specific antigenic markers such as CAR-5 (a glycoprotein contained within intestinal goblet-cells) and M1 (a glycoprotein contained within gastric foveolar cells). For comparison 10 cases of colonic adenocarcinomas and 14 cases of non-AIDC carcinomas of the nose and paranasal sinuses were also examined. The parallel morphological and immuno-histochemical investigations based on specific markers demonstrated that it was impossible to differentiate IADC from large bowel adenocarcinoma for both the structural pattern and antigenic expression. Moreover, AIDC also showed a CAR-5 and M1 immunoreactivity (IR) different from that displayed by the nasal carcinomas of different histotypes. From a histopathological standpoint IADC appears to be a distinctive entity even when compared to salivary gland tumors. In addition, the present immunohistochemical investigation demonstrates that gastric and intestinal glycoproteic antigens (M1 and CAR-5 respectively) occur in the normal nasosinusal mucosa. Both CAR-5 and M1 were observed in the mucous produced by nasal goblet cells with a distribution pattern resembling that of colonic goblet cells. Therefore, the present data confirm the similarity between nasal and colonic goblet cells which has already been pinpointed in previous morphological and ultrastructural studies. The common antigenic expression shared by the naso-sinusal and colonic mucosa might suggest a histogenetic hypothesis alternative to those of the malformative or metaplastic origin of naso-sinusal IADC.
    Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 9(3):297-310. · 0.79 Impact Factor
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    CRISTINA RIVA
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    CRISTINA RIVA

Publication Stats

214 Citations
54.92 Total Impact Points

Institutions

  • 2011–2013
    • Università degli Studi dell'Insubria
      • Department of Biotechnology and Life Sciences (DBSV)
      Varese, Lombardy, Italy
  • 2005–2010
    • University of Insubria
      Varese, Lombardy, Italy
  • 2003
    • Ospedale di Circolo e Fondazione Macchi Varese
      Varese, Lombardy, Italy
  • 1991
    • University of Pavia
      • Department of Public Health, Neuroscience, Experimental and Forensic Medicine
      Ticinum, Lombardy, Italy