Expression of somatostatin receptor subtype 2 and subtype 5 in thyroid malignancies

S. Woelfl; S. Bogner; H. Huber; S. Salaheddin-Nassr; M. Hatzl; C. Decristoforo; I. Virgolini; M. Gabriel

doi:10.3413/Nukmed-0646-14-02

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 2014; 53(05): 179-185
DOI: 10.3413/Nukmed-0646-14-02

Original article

Schattauer GmbH

Expression of somatostatin receptor subtype 2 and subtype 5 in thyroid malignancies

Expression der Somatostatinrezeptor-Subtypen 2 und 5 in Schilddrüsenmalignomen

Autor*innen

S. Woelfl

¹Department of Pathology, General Hospital Linz, Austria
S. Bogner

¹Department of Pathology, General Hospital Linz, Austria
H. Huber

²Department of Nuclear Medicine and Endocrinology, General Hospital Linz, Austria
S. Salaheddin-Nassr

¹Department of Pathology, General Hospital Linz, Austria
M. Hatzl

²Department of Nuclear Medicine and Endocrinology, General Hospital Linz, Austria
C. Decristoforo

³University Clinic of Nuclear Medicine, Medical University Innsbruck, Austria
I. Virgolini

³University Clinic of Nuclear Medicine, Medical University Innsbruck, Austria
M. Gabriel

²Department of Nuclear Medicine and Endocrinology, General Hospital Linz, Austria

³University Clinic of Nuclear Medicine, Medical University Innsbruck, Austria

Abstract

Summary

Aim: To retrospectively analyse the expression of somatostatin receptor subtypes 2 (SSTR 2) and 5 (SSTR 5) in thyroid malignancies, possibly the most relevant subtypes for targeted therapy with somatostatin peptide radioligands. In addition, findings were also correlated with the course of disease. Patients, methods: 87 consecutive patients (59 women, 28 men) with thyroid malignancy were included; 52 had papillary carcinoma, 24 follicular carcinoma, six medullary carcinoma, two poorly differentiated carcinoma and three anaplastic carcinoma. After initial therapy 70 (80.5%) patients showed complete remission, 11 (12.6%) patients partial remission with clinical and biochemical signs of residual disease and six (6.9%) patients progressive disease. The immunohistochemi- cal staining results of the primary malignancy for SSTR 2 and SSTR 5 were semiquanti- tatively assessed and correlated with various outcome parameters. Results: In 10 of 87 (11.49%) thyroid cancer samples SSTR 2 showed positive immunohistochemical expression as compared to 75 of 87 (86.20%) for SSTR 5. All SSTR 2-positive cases expressed SSTR 5. Persistent or recurrent disease was found in 17 of 87 cases (19.54%). Fifty percent (6 /12) of SSTR 5-negative patients showed persistent disease as compared to 14.7 % (11 / 75) of SSTR 5-positive patients: seven of these were exclusively SSTR 5-posi- tive, 4 showed dual expression of SSTR 5 and SSTR 2 (p = 0.01). No case showed only SSTR 2 expression. Conclusions: SSTR 5 was shown to be the main receptor subtype in the analysed differentiated or anaplastic thyroid malignancies, whereas SSTR 2 was found only in a small percentage. Deficient SSTR expression may indicate higher risk for persistent or recurrent disease after initial therapy. For this reason immunohistochemistry can be considered a prognostic marker which should be further validated in prospective studies.

Zusammenfassung

Ziel: In dieser retrospektiven Analyse wurde mittels Immunhistochemie das Expressionsmusters der Somatostatinrezeptor-subtypen 2 (SSTR 2) und 5 (SSTR 5) zur präklinischen Aus- testung hinsichtlich einer möglichen Radionu- klidpeptidtherapie (PRRT) untersucht. Zugleich wurde das individuelle Rezeptorprofil des Primärtumors mit dem Krankheitsverlauf korre- liert. Patienten, Methoden: 87 Patienten (59 Frauen, 28 Männer) mit bösartigen Erkrankungen der Schilddrüse wurden in die Analyse eingeschlossen; davon waren 52 papilläre, 24 follikuläre, 6 medulläre, 2 schlecht-diffe- renzierte und 3 anaplastische Karzinome. Nach der initialen Therapie, in erster Linie Operation und Radiojodtherapie, wurde bei 70 Patienten (80,5%) eine komplette Remission und bei den übrigen 17 Fällen eine persistierende Tumorerkrankung festgestellt, wobei sich bei 6 Patienten (6,9%) in weiterer Folge eine Tumorprogression zeigte. Die im- munhistochemischen Befunde wurden semiquantitative ausgewertet und mit dem Krankheitsverlauf korreliert. Ergebnisse: In 10 von 87 (11.49%) Fällen erfolgte ein positiver Nachweis von SSTR 2 und bei 75 von 87 (86.20%) von SSTR 5. Alle SSTR 2-positiven Fälle zeigten zudem eine nachweisbare Expression von SSTR 5. Bei 14.7% (11 von 75 Patienten) der Fälle mit positiver SSTR 5-Ex- pression wurde eine Tumorprogression nachgewiesen; bei 7 Patienten ausschließlich SSTR 5 und bei 4 Patienten zusätzlich SSTR 2. Ein Rezidivwachstum wurde auch bei 50% (6 von 12 Patienten) der SSTR 5-negativen Fälle beobachtet wurde (p = 0.01). Schlussfolgerung: SSTR 2 ist in einem nur geringen Prozentsatz der Fälle mit differenzierten bzw. anaplastischen Schilddrüsenkarzinomen im- munhistochemisch nachweisbar, weshalb diese Methode keine klinische Relevanz in Bezug auf die Vorhersage einer möglichen PRRT aufweist. Demgegenüber ist eine wesentlich höhere SSTR 5-Expressionsrate nachweisbar, wobei eine fehlende Rezeptorexpression möglicherweise mit einer höheren Wahrscheinlichkeit einer Krankheitspersis- tenz bzw. -progression assoziiert ist. Ob diese Methodik als möglicher Prognosemarker Anwendung finden könnte, bedarf der Klärung in weiteren prospektiv angelegten Studien.

Keywords

Somatostatin receptor expression - immuno - histochemistry - thyroid carcinoma - prognostic marker

Schlüsselwörter

Somatostatinrezeptor-Expression - Immun histochemie - Schilddrüsenkarzinom - Verlaufsbeobachtung

Volltext

Referenzen

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