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Expressions of Somatostatin Receptor Subtypes (SSTR-1, 2, 3, 4 and 5) in Neuroblastic Tumors; Special Reference to Clinicopathological Correlations with International Neuroblastoma Pathology Classification and Outcomes.

Watanabe N, Nakanishi Y, Kinukawa N, Ohni S, Obana Y, Nakazawa A, Nemoto N - Acta Histochem Cytochem (2014)

Bottom Line: The same tendency was observed when surviving and deceased cases were compared, though SSTR-2 expression was well preserved in some of the deceased cases.In conclusion, NTs highly expressed SSTR-1 and/or 2, and expressions of SSTR generally indicate a good prognosis.However, even those in the unfavorable histology group with NBs expressing SSTR are good candidates for molecular targeting therapy using somatostatin analogues.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology, Nihon University School of Medicine , Tokyo, Japan.

ABSTRACT
Somatostatin receptor (SSTR) expressions in neuroblastomas (NBs) have been confirmed employing various methods. High SSTR-2 expression was suggested to be a favorable prognostic marker, though little is known about the relationships between the expressions of SSTR subtypes, other than SSTR-2, and prognosis. We investigated the expressions of all five known SSTR subtypes in 63 neuroblastic tumors (NTs), employing immunohistochemistry, and also conducted quantitative real-time RT-PCR in 37 of these tumors. We evaluated correlations between the expressions of SSTR subtypes and prognosis, based on the International Neuroblastoma Pathology Classification and patient outcomes. More than 90% of cases expressed, at a minimum, SSTR-1 and/or 2. Ganglioneuromas and ganglioneuroblastomas expressed more than two SSTR subtypes. Among NBs, the favorable histology group showed higher SSTR subtype expressions than the unfavorable histology group. The same tendency was observed when surviving and deceased cases were compared, though SSTR-2 expression was well preserved in some of the deceased cases. In conclusion, NTs highly expressed SSTR-1 and/or 2, and expressions of SSTR generally indicate a good prognosis. However, even those in the unfavorable histology group with NBs expressing SSTR are good candidates for molecular targeting therapy using somatostatin analogues.

No MeSH data available.


Related in: MedlinePlus

SSTR expressions in NTs; representative cases. A) SSTR-1, GNB, intermixed tumor; strong positive staining identified in cytoplasm of most tumor cells, corresponding to an IRS of 12. B) SSTR-1, NB, favorable histology group; strong diffuse cytoplasmic staining, IRS 12. C) SSTR-2, GN; moderate positive staining in membranes of more than half of all tumor cells, corresponding to an IRS of 6. D) SSTR-2, NB, unfavorable histology group. Left photo: weak to moderate membranous staining in a portion of the tumor cells, given an IRS of 3. Right photo: different case; strong membranous staining in almost all tumor cells, IRS 12. Both cases are deceased. E) SSTR-3, GN; weak diffuse cytoplasmic staining, IRS 4. F) SSTR-3, NB, favorable histology group; moderate staining in scattered tumor cells, IRS 2. G) SSTR-4, GN; moderate diffuse cytoplasmic staining, IRS 8. H) SSTR-4, NB, favorable histology group; moderate positive staining in cytoplasm of more than half of tumor cells, IRS 6. Bars=50 μm.
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Figure 3: SSTR expressions in NTs; representative cases. A) SSTR-1, GNB, intermixed tumor; strong positive staining identified in cytoplasm of most tumor cells, corresponding to an IRS of 12. B) SSTR-1, NB, favorable histology group; strong diffuse cytoplasmic staining, IRS 12. C) SSTR-2, GN; moderate positive staining in membranes of more than half of all tumor cells, corresponding to an IRS of 6. D) SSTR-2, NB, unfavorable histology group. Left photo: weak to moderate membranous staining in a portion of the tumor cells, given an IRS of 3. Right photo: different case; strong membranous staining in almost all tumor cells, IRS 12. Both cases are deceased. E) SSTR-3, GN; weak diffuse cytoplasmic staining, IRS 4. F) SSTR-3, NB, favorable histology group; moderate staining in scattered tumor cells, IRS 2. G) SSTR-4, GN; moderate diffuse cytoplasmic staining, IRS 8. H) SSTR-4, NB, favorable histology group; moderate positive staining in cytoplasm of more than half of tumor cells, IRS 6. Bars=50 μm.

Mentions: IHC expressions of SSTR subtypes classified by INPC are shown in Table 5. All GNs and GNBs showed 100% SSTR-1, 2 and 4 expressions. In NBs, the rates of positivity for SSTR 1, 2, 3 and 4 were higher in the favorable than in the unfavorable histology group and the differences were statistically significant. These results indicated the tendency for morphologically differentiated tumors and the favorable histology group to express more SSTR subtypes. Semi-quantitative comparison using the IRS system showed GNs and GNBs to have higher scores than NBs with the SSTR-1, 3 and 4 subtypes (Fig. 2). As to SSTR-2, however, the scores were not particularly high for GNs and GNBs. In NBs, the favorable histology group showed higher point totals than the unfavorable histology group, with significant differences in SSTR-1, 2 and 4. Representative positive cases are shown in Fig. 3. In general, large cells which appeared to be more differentiated tended to stain well. Expressions of SSTR subtypes in normal tissues from the adrenal medulla and sympathetic ganglia were quite similar to those of GNs and GNBs, with the expression rates being 100% for SSTR-1, approximately 90% for SSTR-2, approximately 40% for SSTR-3, 100% for SSTR-4 and 0% for SSTR-5.


Expressions of Somatostatin Receptor Subtypes (SSTR-1, 2, 3, 4 and 5) in Neuroblastic Tumors; Special Reference to Clinicopathological Correlations with International Neuroblastoma Pathology Classification and Outcomes.

Watanabe N, Nakanishi Y, Kinukawa N, Ohni S, Obana Y, Nakazawa A, Nemoto N - Acta Histochem Cytochem (2014)

SSTR expressions in NTs; representative cases. A) SSTR-1, GNB, intermixed tumor; strong positive staining identified in cytoplasm of most tumor cells, corresponding to an IRS of 12. B) SSTR-1, NB, favorable histology group; strong diffuse cytoplasmic staining, IRS 12. C) SSTR-2, GN; moderate positive staining in membranes of more than half of all tumor cells, corresponding to an IRS of 6. D) SSTR-2, NB, unfavorable histology group. Left photo: weak to moderate membranous staining in a portion of the tumor cells, given an IRS of 3. Right photo: different case; strong membranous staining in almost all tumor cells, IRS 12. Both cases are deceased. E) SSTR-3, GN; weak diffuse cytoplasmic staining, IRS 4. F) SSTR-3, NB, favorable histology group; moderate staining in scattered tumor cells, IRS 2. G) SSTR-4, GN; moderate diffuse cytoplasmic staining, IRS 8. H) SSTR-4, NB, favorable histology group; moderate positive staining in cytoplasm of more than half of tumor cells, IRS 6. Bars=50 μm.
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Related In: Results  -  Collection

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Figure 3: SSTR expressions in NTs; representative cases. A) SSTR-1, GNB, intermixed tumor; strong positive staining identified in cytoplasm of most tumor cells, corresponding to an IRS of 12. B) SSTR-1, NB, favorable histology group; strong diffuse cytoplasmic staining, IRS 12. C) SSTR-2, GN; moderate positive staining in membranes of more than half of all tumor cells, corresponding to an IRS of 6. D) SSTR-2, NB, unfavorable histology group. Left photo: weak to moderate membranous staining in a portion of the tumor cells, given an IRS of 3. Right photo: different case; strong membranous staining in almost all tumor cells, IRS 12. Both cases are deceased. E) SSTR-3, GN; weak diffuse cytoplasmic staining, IRS 4. F) SSTR-3, NB, favorable histology group; moderate staining in scattered tumor cells, IRS 2. G) SSTR-4, GN; moderate diffuse cytoplasmic staining, IRS 8. H) SSTR-4, NB, favorable histology group; moderate positive staining in cytoplasm of more than half of tumor cells, IRS 6. Bars=50 μm.
Mentions: IHC expressions of SSTR subtypes classified by INPC are shown in Table 5. All GNs and GNBs showed 100% SSTR-1, 2 and 4 expressions. In NBs, the rates of positivity for SSTR 1, 2, 3 and 4 were higher in the favorable than in the unfavorable histology group and the differences were statistically significant. These results indicated the tendency for morphologically differentiated tumors and the favorable histology group to express more SSTR subtypes. Semi-quantitative comparison using the IRS system showed GNs and GNBs to have higher scores than NBs with the SSTR-1, 3 and 4 subtypes (Fig. 2). As to SSTR-2, however, the scores were not particularly high for GNs and GNBs. In NBs, the favorable histology group showed higher point totals than the unfavorable histology group, with significant differences in SSTR-1, 2 and 4. Representative positive cases are shown in Fig. 3. In general, large cells which appeared to be more differentiated tended to stain well. Expressions of SSTR subtypes in normal tissues from the adrenal medulla and sympathetic ganglia were quite similar to those of GNs and GNBs, with the expression rates being 100% for SSTR-1, approximately 90% for SSTR-2, approximately 40% for SSTR-3, 100% for SSTR-4 and 0% for SSTR-5.

Bottom Line: The same tendency was observed when surviving and deceased cases were compared, though SSTR-2 expression was well preserved in some of the deceased cases.In conclusion, NTs highly expressed SSTR-1 and/or 2, and expressions of SSTR generally indicate a good prognosis.However, even those in the unfavorable histology group with NBs expressing SSTR are good candidates for molecular targeting therapy using somatostatin analogues.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology, Nihon University School of Medicine , Tokyo, Japan.

ABSTRACT
Somatostatin receptor (SSTR) expressions in neuroblastomas (NBs) have been confirmed employing various methods. High SSTR-2 expression was suggested to be a favorable prognostic marker, though little is known about the relationships between the expressions of SSTR subtypes, other than SSTR-2, and prognosis. We investigated the expressions of all five known SSTR subtypes in 63 neuroblastic tumors (NTs), employing immunohistochemistry, and also conducted quantitative real-time RT-PCR in 37 of these tumors. We evaluated correlations between the expressions of SSTR subtypes and prognosis, based on the International Neuroblastoma Pathology Classification and patient outcomes. More than 90% of cases expressed, at a minimum, SSTR-1 and/or 2. Ganglioneuromas and ganglioneuroblastomas expressed more than two SSTR subtypes. Among NBs, the favorable histology group showed higher SSTR subtype expressions than the unfavorable histology group. The same tendency was observed when surviving and deceased cases were compared, though SSTR-2 expression was well preserved in some of the deceased cases. In conclusion, NTs highly expressed SSTR-1 and/or 2, and expressions of SSTR generally indicate a good prognosis. However, even those in the unfavorable histology group with NBs expressing SSTR are good candidates for molecular targeting therapy using somatostatin analogues.

No MeSH data available.


Related in: MedlinePlus