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High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis.

Thomas A, Chen Y, Steinberg SM, Luo J, Pack S, Raffeld M, Abdullaev Z, Alewine C, Rajan A, Giaccone G, Pastan I, Miettinen M, Hassan R - Oncotarget (2015)

Bottom Line: Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases.High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014).High mesothelin expression was strongly associated with mutant KRAS (P < 0.0001) and wild-type EGFR (P = 0.002).

View Article: PubMed Central - PubMed

Affiliation: Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT
Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases. In this study, we used prospectively obtained clinical and pathological data to characterize mesothelin expression in advanced lung adenocarcinoma. Tissue was obtained from patients who underwent molecular profiling of potentially actionable genes on a trial of molecular profiling and targeted therapies in advanced thoracic malignancies. We immunohistochemically evaluated the intensity, and the percentage of cells expressing mesothelin in 93 advanced lung adenocarcinomas. The evaluation was blinded for molecular data and outcome. Mutations of EGFR, KRAS, BRAF, AKT1, PIK3CA and HER2 were assessed by pyrosequencing; HER2 amplification and ALK translocation were assessed by fluorescence in situ hybridization. 53% of advanced lung adenocarcinomas expressed mesothelin to some degree; high mesothelin expression, defined as mesothelin positivity in more than 25% of cells, was found in 24% of patients. High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014). High mesothelin expression was strongly associated with mutant KRAS (P < 0.0001) and wild-type EGFR (P = 0.002). Our results provide strong rationale to explore anti-mesothelin targeted therapies in advanced lung adenocarcinoma especially in the KRAS-mutant subgroup.

No MeSH data available.


Related in: MedlinePlus

Tumor expression of mesothelin in lung adenocarcinoma was evaluated using immunohistochemistryRepresentative images are depicted (original magnification x400). Focal cytoplasmic immunostaining of 2+ intensity in 15% cells A., membranous and cytoplasmic immunostaining of 2+ intensity in 1% cells B., membranous immunostaining in of 3+ intensity in 30% cells C., membranous and cytoplasmic immunostaining of 3+ intensity in 60% cells D., membranous and cytoplasmic immunostaining of 3+ intensity in 80% cells E., membranous and cytoplasmic immunostaining of 3+ intensity in 100% cells F.
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Figure 2: Tumor expression of mesothelin in lung adenocarcinoma was evaluated using immunohistochemistryRepresentative images are depicted (original magnification x400). Focal cytoplasmic immunostaining of 2+ intensity in 15% cells A., membranous and cytoplasmic immunostaining of 2+ intensity in 1% cells B., membranous immunostaining in of 3+ intensity in 30% cells C., membranous and cytoplasmic immunostaining of 3+ intensity in 60% cells D., membranous and cytoplasmic immunostaining of 3+ intensity in 80% cells E., membranous and cytoplasmic immunostaining of 3+ intensity in 100% cells F.

Mentions: The intensity and percentage of cells expressing mesothelin in advanced lung adenocarcinoma is shown in Table 2. Of the 93 tumors tested, any expression of mesothelin was observed in 49 (53%) and high expression in 22 (24%). Figure 2 shows representative images of mesothelin expression in lung cancers. Mesothelin expression was observed in the cytoplasm alone in 10 (20%), membrane alone in 14 (29%) and in both membrane and cytoplasm in 25 (51%).


High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis.

Thomas A, Chen Y, Steinberg SM, Luo J, Pack S, Raffeld M, Abdullaev Z, Alewine C, Rajan A, Giaccone G, Pastan I, Miettinen M, Hassan R - Oncotarget (2015)

Tumor expression of mesothelin in lung adenocarcinoma was evaluated using immunohistochemistryRepresentative images are depicted (original magnification x400). Focal cytoplasmic immunostaining of 2+ intensity in 15% cells A., membranous and cytoplasmic immunostaining of 2+ intensity in 1% cells B., membranous immunostaining in of 3+ intensity in 30% cells C., membranous and cytoplasmic immunostaining of 3+ intensity in 60% cells D., membranous and cytoplasmic immunostaining of 3+ intensity in 80% cells E., membranous and cytoplasmic immunostaining of 3+ intensity in 100% cells F.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4484487&req=5

Figure 2: Tumor expression of mesothelin in lung adenocarcinoma was evaluated using immunohistochemistryRepresentative images are depicted (original magnification x400). Focal cytoplasmic immunostaining of 2+ intensity in 15% cells A., membranous and cytoplasmic immunostaining of 2+ intensity in 1% cells B., membranous immunostaining in of 3+ intensity in 30% cells C., membranous and cytoplasmic immunostaining of 3+ intensity in 60% cells D., membranous and cytoplasmic immunostaining of 3+ intensity in 80% cells E., membranous and cytoplasmic immunostaining of 3+ intensity in 100% cells F.
Mentions: The intensity and percentage of cells expressing mesothelin in advanced lung adenocarcinoma is shown in Table 2. Of the 93 tumors tested, any expression of mesothelin was observed in 49 (53%) and high expression in 22 (24%). Figure 2 shows representative images of mesothelin expression in lung cancers. Mesothelin expression was observed in the cytoplasm alone in 10 (20%), membrane alone in 14 (29%) and in both membrane and cytoplasm in 25 (51%).

Bottom Line: Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases.High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014).High mesothelin expression was strongly associated with mutant KRAS (P < 0.0001) and wild-type EGFR (P = 0.002).

View Article: PubMed Central - PubMed

Affiliation: Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT
Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases. In this study, we used prospectively obtained clinical and pathological data to characterize mesothelin expression in advanced lung adenocarcinoma. Tissue was obtained from patients who underwent molecular profiling of potentially actionable genes on a trial of molecular profiling and targeted therapies in advanced thoracic malignancies. We immunohistochemically evaluated the intensity, and the percentage of cells expressing mesothelin in 93 advanced lung adenocarcinomas. The evaluation was blinded for molecular data and outcome. Mutations of EGFR, KRAS, BRAF, AKT1, PIK3CA and HER2 were assessed by pyrosequencing; HER2 amplification and ALK translocation were assessed by fluorescence in situ hybridization. 53% of advanced lung adenocarcinomas expressed mesothelin to some degree; high mesothelin expression, defined as mesothelin positivity in more than 25% of cells, was found in 24% of patients. High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014). High mesothelin expression was strongly associated with mutant KRAS (P < 0.0001) and wild-type EGFR (P = 0.002). Our results provide strong rationale to explore anti-mesothelin targeted therapies in advanced lung adenocarcinoma especially in the KRAS-mutant subgroup.

No MeSH data available.


Related in: MedlinePlus