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EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides.

Carlsson J, Wester K, De La Torre M, Malmström PU, Gårdmark T - Radiol Oncol (2015)

Bottom Line: Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose.It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy.This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

ABSTRACT

Background: There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radio-nuclides to the extracellular domain of the receptors is potentially a better possibility.

Methods: EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose.

Results: EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients.

Conclusions: At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

No MeSH data available.


Related in: MedlinePlus

Examples of immunohistochemical EGFR-staining (brown) of samples from metastasized urinary bladder cancers. (A) Primary tumor. (B) Regional (local) lymph node metastasis (from the same patient as in A). Note the large number of lymphocytes (small blue haematoxylin stained nuclei to the right). (C) Primary tumor. (D) Colon metastasis (classified as distant). All samples were scored 3+ and EGFR-positive. All bars correspond to 100μm.
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f1-rado-49-01-50: Examples of immunohistochemical EGFR-staining (brown) of samples from metastasized urinary bladder cancers. (A) Primary tumor. (B) Regional (local) lymph node metastasis (from the same patient as in A). Note the large number of lymphocytes (small blue haematoxylin stained nuclei to the right). (C) Primary tumor. (D) Colon metastasis (classified as distant). All samples were scored 3+ and EGFR-positive. All bars correspond to 100μm.

Mentions: The EGFR determinations are shown in Table 2. EGFR was positive in 51/72 (71%) of the primary tumors and 50/72 (69%) of the corresponding metastases. The regional (local) and the distant metastases were EGFR-positive in 21/28 (75%) and 29/44 (66%) of the cases, respectively. Considering only the EGFR-positive primary tumors (n=51) the corresponding metastases were EGFR-positive in 44/51 (86%) of the cases. Examples of EGFR-positive tumor cells are shown in Figure 1.


EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides.

Carlsson J, Wester K, De La Torre M, Malmström PU, Gårdmark T - Radiol Oncol (2015)

Examples of immunohistochemical EGFR-staining (brown) of samples from metastasized urinary bladder cancers. (A) Primary tumor. (B) Regional (local) lymph node metastasis (from the same patient as in A). Note the large number of lymphocytes (small blue haematoxylin stained nuclei to the right). (C) Primary tumor. (D) Colon metastasis (classified as distant). All samples were scored 3+ and EGFR-positive. All bars correspond to 100μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362606&req=5

f1-rado-49-01-50: Examples of immunohistochemical EGFR-staining (brown) of samples from metastasized urinary bladder cancers. (A) Primary tumor. (B) Regional (local) lymph node metastasis (from the same patient as in A). Note the large number of lymphocytes (small blue haematoxylin stained nuclei to the right). (C) Primary tumor. (D) Colon metastasis (classified as distant). All samples were scored 3+ and EGFR-positive. All bars correspond to 100μm.
Mentions: The EGFR determinations are shown in Table 2. EGFR was positive in 51/72 (71%) of the primary tumors and 50/72 (69%) of the corresponding metastases. The regional (local) and the distant metastases were EGFR-positive in 21/28 (75%) and 29/44 (66%) of the cases, respectively. Considering only the EGFR-positive primary tumors (n=51) the corresponding metastases were EGFR-positive in 44/51 (86%) of the cases. Examples of EGFR-positive tumor cells are shown in Figure 1.

Bottom Line: Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose.It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy.This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

ABSTRACT

Background: There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radio-nuclides to the extracellular domain of the receptors is potentially a better possibility.

Methods: EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose.

Results: EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients.

Conclusions: At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

No MeSH data available.


Related in: MedlinePlus