Genetic Markers in Sporadic Tumors

Tamborini, Elena; Perrone, Francesco; Frattini, Milo; Negri, Tiziana; Aiello, Antonella; Gloghini, Annunziata; Carbone, Antonino; Pilotti, Silvana

doi:10.1007/978-1-59745-470-4_3

Cited by 2 publications

(2 citation statements)

References 208 publications

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“…A type of in situ FL has been described, in which t(14;18)‐positive cells expressing BCL2 are observed in histologically abnormal follicles present in lymph node biopsy specimens from persons without overt disease (Figure ). Noteworthy, BCL2 point mutations and amplification also may lead to increased protein production, although t(14;18) translocation is the main mechanism of BCL2 gene activation, which leads to increased BCL2 production .…”

Section: In Situ Fl As a Distinct Step Of Molecular Pathogenesis Of Flmentioning

confidence: 99%

In situ follicular lymphoma: pathologic characteristics and diagnostic features

Carbone

Gloghini

Santoro

2011

Hematological Oncology

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The diagnosis of in situ follicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescence in situ hybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal follicles is notable for its high-level and uniform intensity. In situ FL may be associated with overt FL or with lymphomas other than FL or with other malignancies. The crucial point relies on distinguishing in situ FL arising in asymptomatic patients from cases with presence of lymphoma at the same or other sites. Other open questions remain on the frequency with which in situ FLs occur and the frequency of concomitant systemic disease.

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Section: In Situ Fl As a Distinct Step Of Molecular Pathogenesis Of Flmentioning

confidence: 99%

In situ follicular lymphoma: pathologic characteristics and diagnostic features

Carbone

Gloghini

Santoro

2011

Hematological Oncology

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“…Extensive clinical studies have shown that overexpression of HER2/neu is found in 20-40% of patients with breast, ovarian, endometrial, gastric, bladder, prostate, and lung cancers. Studies clearly demonstrate that HER2/neu overexpression correlates with the prevalence of metastatic spread of many tumors and is generally considered to be a poor prognostic indicator [6][7][8][9] .Since HER2/neu overexpression by tumor cells is quite speci fi c, therapies directed against this receptor have rapidly gained recognition for their selectivity and ef fi cacy in the clinical setting. While targeting of HER2/neu with humanized antibodies such as trastuzumab (Herceptin; Genentech) has proven to be an effective approach for the treatment of HER2/neu-overexpressing breast cancers, there are a signi fi cant number of patients with HER2/neu-positive tumors who do not respond or who acquire resistance to this therapy [10][11][12][13] .…”

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Design, Development, and Characterization of Recombinant Immunotoxins Targeting HER2/neu

Cao

Rosenblum

2012

Antibody-Drug Conjugates and Immunotoxins

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BackgroundThe human epidermal growth factor receptor 2 (HER2), also known as ErbB2, c-erbB2, or HER2/neu, was initially discovered in 1985 by two independent laboratories [ 1,2 ] . HER2/neu is a 185 kDa (1,255 aa) transmembrane receptor encompassing an intracellular tyrosine kinase domain and an extracellular ligand binding component [3][4][5] . Extensive clinical studies have shown that overexpression of HER2/neu is found in 20-40% of patients with breast, ovarian, endometrial, gastric, bladder, prostate, and lung cancers. Studies clearly demonstrate that HER2/neu overexpression correlates with the prevalence of metastatic spread of many tumors and is generally considered to be a poor prognostic indicator [6][7][8][9] .Since HER2/neu overexpression by tumor cells is quite speci fi c, therapies directed against this receptor have rapidly gained recognition for their selectivity and ef fi cacy in the clinical setting. While targeting of HER2/neu with humanized antibodies such as trastuzumab (Herceptin; Genentech) has proven to be an effective approach for the treatment of HER2/neu-overexpressing breast cancers, there are a signi fi cant number of patients with HER2/neu-positive tumors who do not respond or who acquire resistance to this therapy [10][11][12][13] . Therefore, there is a need for novel therapeutic approaches using HER2/neu not only as a target for interfering with the growth factor signaling component but also for receptor-mediated delivery of cytotoxic agents.Immunotoxins are a novel approach for the development of highly speci fi c, targeted agents and which generally employ a powerful class of protein toxins [ 14,15 ] . These include plant toxins such as ricin [16][17][18][19][20][21][22][23][24][25] , saporin [26][27][28][29] , and gelonin [30][31][32] Diphtheria toxin (DT) [ 33 ] and Pseudomonas exotoxin (PE) [34][35][36][37][38][39][40][41][42][43] , which ADP ribosylate elongation factor 2 (EIF2). Anti-HER2/neu immunotoxins have been created initially by chemically conjugating an antibody to a whole protein toxin or, for more selective activity, using a protein toxin devoid of its natural binding domain [ 19,23, 30,44 ] . Technical advances in antibody engineering now enable us to produce various antibodies or antibody fragments in Escherichia coli , and as a result, HER2/neu-speci fi c antibodies and engineered fragments thereof have been developed to deliver various toxins to HER2/neu-positive tumor cells [45][46][47][48][49][50][51] . Various anti-HER2/neu immunotoxins which have been developed or are currently under evaluation are described in Table 18.1 . Antibody-Drug Conjugates: Promise and ProblemsAntibody-based therapeutics is of growing signi fi cance for cancer therapy. To date, two of the most promising strategies to enhance the antitumor activity of antibodies are antibody-drug conjugates (ADCs) and antibodies (or fragments) chemically conjugated or genetically fused to various toxins (immunotoxins).One successful application of the ADC approach is Trastuzumab-DM1. This is a cov...

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Genetic Markers in Sporadic Tumors

Cited by 2 publications

References 208 publications

In situ follicular lymphoma: pathologic characteristics and diagnostic features

In situ follicular lymphoma: pathologic characteristics and diagnostic features

Design, Development, and Characterization of Recombinant Immunotoxins Targeting HER2/neu

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