Abstract
BackgroundTo characterize the expression of the membrane transporter NaPi2b and antigen targeted by the MX35 antibody in ovarian tumor samples. The current interest to develop monoclonal antibody based therapy of ovarian cancer by targeting NaPi2b emphasizes the need for detailed knowledge and characterization of the expression pattern of this protein. For the majority of patients with ovarian carcinoma the risk of being diagnosed in late stages with extensive loco-regional spread disease is substantial, which stresses the need to develop improved therapeutic agents.MethodsThe gene and protein expression of SLC34A2/NaPi2b were analyzed in ovarian carcinoma tissues by QPCR (n = 73) and immunohistochemistry (n = 136). The expression levels and antigen localization were established and compared to the tumor characteristics and clinical data.ResultsPositive staining for the target protein, NaPi2b was detected for 93% of the malignant samples, and we identified three separate distribution patterns of the antigen within the tumors, based on the localization of NaPi2b. There were differences in the staining intensity as well as the distribution pattern when comparing the tumor grade and histology, the mucinous tumors presented a significantly lower expression of both the targeted protein and its related gene.ConclusionOur study identified differences regarding the level of the antigen expression between tumor grade and histology. We have identified differences in the antigen localization between borderline tumors, type 1 and type 2 tumors, and suggest that a pathological evaluation of NaPi2b in the tumors would be helpful in order to know which patients that would benefit from this targeted therapy.
Highlights
To characterize the expression of the membrane transporter NaPi2b and antigen targeted by the MX35 antibody in ovarian tumor samples
In the situation of using alpha emitting radionuclides i.e. targeted alpha therapy (TAT) for ovarian cancer, recently explored for other antigenic targets than NaPi2b, a solution containing antibodies labeled with α-particles emitting radionuclide is injected locally into the peritoneal cavity [16]
Due to the short range a too large heterogeneity of the intratumoral distribution and/ or intensity of the antigen could impact the therapeutic outcome. This has been shown on epithelial ovarian cancer (EOC) biopsies where the tumor uptake (%ID/g) radiolabeled MX35 could vary a factor of 20 in-between samples and that the activity uptake of MX35 correlated both with level and intensity of the MX35-antigen expression, as analyzed by autoradiography and immunohistochemistry [17]
Summary
To characterize the expression of the membrane transporter NaPi2b and antigen targeted by the MX35 antibody in ovarian tumor samples. The current interest to develop monoclonal antibody based therapy of ovarian cancer by targeting NaPi2b emphasizes the need for detailed knowledge and characterization of the expression pattern of this protein. Due to the short range a too large heterogeneity of the intratumoral distribution and/ or intensity of the antigen could impact the therapeutic outcome This has been shown on epithelial ovarian cancer (EOC) biopsies where the tumor uptake (%ID/g) radiolabeled MX35 could vary a factor of 20 in-between samples and that the activity uptake of MX35 correlated both with level and intensity of the MX35-antigen expression, as analyzed by autoradiography and immunohistochemistry [17]. Strategies to predict and counteract for the impact of heterogeneity are currently being investigated, including parameters like radiation crossfire and specific activity of the radiopharmaceutical [20]
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