Immunolocalization of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult serous membranes and mesotheliomas

Petričević, Joško; Punda, Hrvoje; Brakus, Snjezana Mardesic; Vukojević, Katarina; Govorko, Danijela Kalibović; Alfirević, Darko; Kvesić, Ante; Saraga-Babić, Mirna

doi:10.1016/j.acthis.2011.08.009

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…In serous ovarian carcinoma, nestin was detected in 33% of the tissues and its overexpression correlated with cisplatin-based CT resistance and shorter OS [ 20 ]. In MPM, any nestin expression was observed in 13% of the tumor cells of 6 epithelioid MPM [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent work on nestin, mesothelin and epithelial membrane antigen (EMA) expression in developing and adult serous membranes indicated that superficial pleural mesothelial cells are always nestin negative, whereas in the submesothelial layer cells nestin expression decreases during development. Nestin protein expression was immunohistochemically detected in 13% of the tumor cells of 6 epithelioid mesotheliomas [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

et al. 2015

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BackgroundThe epithelioid and sarcomatoid histologic variants of malignant pleural mesothelioma (MPM) can be considered as E- and M-parts of the epithelial-mesenchymal transition (EMT) axis; the biphasic being an intermediate. EMT is associated with an increase of stem cell (SC) traits. We correlated the neural crest SC marker nestin and the EMT marker periostin with histology, type of neo-adjuvant chemotherapy (CT) and overall survival (OS) of MPM patients.Patients and MethodsTumor tissues of a historic cohort 1 (320 patients) and an intended induction chemotherapy followed by extrapleural pneumonectomy (EPP) cohort 2 (145 patients) were immunohistochemically H-scored (intensity of immunoreactivity multiplied by frequency of stained cells). Paired chemo-naïve biopsies and -treated surgical specimens were available for 105/145 patients. CT included platinum/gemcitabine (Pla/Gem) or platinum/pemetrexed (Pla/Pem).ResultsExpression of any cytosolic nestin progressively increased from epithelioid to biphasic to sarcomatoid MPM in cohort 1, whereas the diagnostic markers calretinin and podoplanin decreased. In cohort 2, Pla/Pem CT increased the expression level of nestin in comparison to Pla/Gem, whereas the opposite was found for periostin. In Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid. In addition to non-epithelioid histology, any expression of nestin in chemo-naïve biopsies (median overall survival: 22 vs. 17 months) and chemo-treated surgical specimens (18 vs. 12 months) as well as high periostin in biopsies (23 vs. 15 months) were associated with poor prognosis. In the multivariate survival analysis, any nestin expression in chemo-naïve biopsies proved to be an independent prognosticator against histology. In both pre- and post-CT situations, the combination of nestin or periostin expression with non-epithelioid histology was particularly/ dismal (all p-values <0.05).ConclusionsThe SC marker nestin and the EMT marker periostin allow for further prognostic stratification among histologic variants of MPM. Their expression level is influenced by neo-adjuvant chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

et al. 2015

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“…We have previously developed methods for selecting phage human antibody display libraries directly on tumor issues derived from patient specimens (An et al, 2008;Bidlingmaier et al, 2009;Ruan et al, 2006) following counter-selection on normal tissues and cells. In the case of mesothelioma, we identified a panel of novel human a single-chain variable fragments (scFvs) that bind to both epithelial and sarcomatous types but not normal mesothelium (An et al, 2008), a clear differentiation from antibodies binding to mesothelin that is expressed by epithelial mesothelioma but rarely by sarcomatous mesothelioma (Ordonez, 2003), and also by normal mesothelium (Petricevic et al, 2012). One of the antibodies, M25, showed the highest specificity, binding to a novel cell surface target expressed by all subtypes of mesothelioma (An et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen

Zhang

Bidlingmaier

et al. 2020

Cancer Research

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It has been challenging to identify tumor-specific cell surface antigens as the vast majority of tumor-associated antigens are also expressed by some normal tissues. In the course of our study on mesothelioma, we identified a highly specific tumor cell surface antigen that can be targeted for therapy development. Mesothelioma is caused by malignant transformation of the mesothelium, incurable and categorized into three histological subtypes, epithelioid, biphasic and sarcomatoid. To identity novel mesothelioma cell surface antigens with broad subtype coverage and high tissue specificity, we have previously selected phage antibody display libraries on live mesothelioma cells and tissues following counter-selection on normal cells, and identified a panel of human antibodies that bind all subtypes of mesothelioma but not normal mesothelium. One of the antibodies, M25, showed high specificity, and we hereby report the identification of the M25 antigen as ALPPL2. We performed immunohistochemistry on normal human tissues and found that ALPPL2 is expressed only on placental trophoblasts but not any other normal tissues. This exquisite tissue specificity and broad tumor type coverage suggests that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, we developed an ALPPL2-targeted antibodydrug conjugate and demonstrated potent and specific tumor killing in vitro and in vivo against both epithelioid and sarcomatoid mesothelioma. Thus ALPPL2 belongs to a rare class of cell surface antigens that can be said as being truly tumor specific and is well suited for therapy development against ALPPL2 expressing tumors..

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Apoptotic pathways in ovarian surface epithelium of human embryos during embryogenesis and carcinogenesis: Close relationship of developmental plasticity and neoplasm

et al. 2014

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Immunolocalization of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult serous membranes and mesotheliomas

Cited by 4 publications

References 44 publications

Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen

Apoptotic pathways in ovarian surface epithelium of human embryos during embryogenesis and carcinogenesis: Close relationship of developmental plasticity and neoplasm

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