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Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms:
Andrea Gillis1, Rui Zheng-Pywell1, Chandler McLeod1
1Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Abstract:
Somatostatin receptor type 2 (SSTR2) and thyroid-stimulating hormone receptor (TSHR) display variable expression in primary thyroid tumors and have been implicated as theranostic targets. This study was designed to explore the differential expression of SSTR2 and TSHR in oncocytic (Hurthle cell) carcinoma (OC) vs oncocytic adenoma (OA). We performed a retrospective review for oncocytic neoplasms treated at our institution from 2012 to 2019. Formalin-fixed paraffin-embedded tissue blocks were used for tissue microarray construction. Tissue microarray blocks were cut into 5-μm sections and stained with anti-SSTR2 and anti-TSHR antibodies. Immunostains were analyzed by 3 independent pathologists. χ2 and logistic regression analysis were used to analyze clinical and pathologic variables. Sixty-seven specimens were analyzed with 15 OA and 52 OC. The mean age was 57 years, 61.2% were women, and 70% were White. SSTR2 positivity was noted in 2 OA (13%) and 15 OC (28%; 10 primary, 4 recurrent, and 1 metastatic) (P = .22). TSHR positivity was noted in 11 OA (73%) and 32 OC (62%; 31 primary and 1 metastatic) (P = .40). Those who presented with or developed clinical recurrence/metastasis were more likely to be SSTR2-positive (50% vs 21%; P = .04) and TSHR-negative (64.3% vs 28.9%; P = .02) than primary OC patients. Widely invasive OC was more likely to be SSTR2-positive compared to all other OC subtypes (minimally invasive and angioinvasive) (P = .003). For all patients with OC, TSHR positivity was inversely correlated with SSTR2 positivity (odds ratio, 0.12; CI, 0.03-0.43; P = .006). This relationship was not seen in the patients with OA (odds ratio, 0.30; CI, 0.01-9.14; P = .440). Our results show that recurrent/metastatic OC was more likely to be SSTR2-positive and TSHR-negative than primary OC. Patients with OC displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in patients with OA. This may be a key relationship that can be used to prognosticate and treat OCs.
Insights
Thyroid cancer recurrence is linked to higher somatostatin receptor type 2 (SSTR2) and lower thyroid-stimulating hormone receptor (TSHR) expression. This inverse relationship in oncocytic carcinoma (OC) may aid in prognostication and treatment.
Area of Science:
- Endocrinology
- Oncology
- Pathology
Background:
- Thyroid-stimulating hormone receptor (TSHR) and somatostatin receptor type 2 (SSTR2) are potential theranostic targets in thyroid tumors.
- Their expression varies in primary thyroid cancers, necessitating further investigation into their roles in specific subtypes.
Purpose of the Study:
- To investigate the differential expression of SSTR2 and TSHR in oncocytic carcinoma (OC) versus oncocytic adenoma (OA).
- To determine the correlation between SSTR2 and TSHR expression and clinical outcomes, including recurrence and metastasis in OC.
Main Methods:
- Retrospective review of 67 oncocytic neoplasms (15 OA, 52 OC) treated between 2012 and 2019.
- Tissue microarray construction and immunohistochemical staining for SSTR2 and TSHR.
- Statistical analysis using chi-squared and logistic regression to evaluate expression patterns and clinical variables.
Main Results:
- SSTR2 positivity was observed in 13% of OA and 28% of OC.
- TSHR positivity was noted in 73% of OA and 62% of OC.
- Recurrent/metastatic OC showed higher SSTR2 positivity (50% vs 21%) and lower TSHR positivity (64.3% vs 28.9%) compared to primary OC.
- Widely invasive OC was more likely to be SSTR2-positive (P=.003).
- An inverse correlation between TSHR and SSTR2 positivity was significant in OC (OR, 0.12; P=.006) but not in OA.
Conclusions:
- Recurrent and metastatic oncocytic carcinoma exhibits a distinct SSTR2-positive and TSHR-negative profile compared to primary OC.
- The inverse relationship between SSTR2 and TSHR expression in OC may serve as a prognostic biomarker.
- Further research into these receptors could inform targeted theranostic strategies for oncocytic thyroid cancers.
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